A Phase 2 Study, Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate the Efficacy, Tolerability, and Safety of Belumosudil in Subjects With Moderate/Severe Chronic Plaque Psoriasis Who Are Candidates for Systemic Therapy or Phototherapy
Phase: PHASE2
Conditions: Chronic Plaque Psoriasis
Sponsor: Kadmon Corporation, LLC

 
 
Protocol Number:  KD025-211 
 
Document Title:  A Phase 2, Randomized, Double-blind, Placebo-controlled, 
Dose-finding Study to Evaluate the Safety, Tolerability, and Efficacy of KD025 in 
Adult Subjects with Moderate to Severe Chronic Plaque Psoriasis Who are 
Candidates for Systemic Therapy or Phototherapy 
 
Version Number:  Amendment #2 
 
Date of Document:  12 March 2019 
 
NCT Number:  NCT02852967 

• 
Kadmone 
CLINICAL STUDY PROTOCOL 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 
Dose-Finding Study to Evaluate the Safety, Tolerability, and 
Efficacy of KD025 in Adult Subjects with Moderate to Severe 
Chronic Plaque Psoriasis who are Candidates for Systemic Therapy 
or Phototherapy 
Protocol Number: 
Study Drug: 
IND Number: 
Phase 
Sponsor: 
KDO25-211 
KDO25 
120787 
2 
Kadmon Corporation 
450 East 29th Street 
New York, NY 10016 
Medical Monitor: 	
John L Ryan, PhD, MD 
Date of Protocol: 	
Original, 24 May 2016 
Amendment No. 1 	
21 February 2017 
Amendment No. 2 	
12 March 2019 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property of Kadmon Corporation 
and any unauthorized use or disclosure of such information without the prior written authorization of 
Kadmon Corporation is expressly prohibited. 

KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
PROCEDURES IN CASE OF EMERGENCY 
Serious and Unexpected Adverse Events  
Any serious adverse event (SAE)* or suspected unexpected serious adverse reaction (SUSAR)** 
occurring in a subject while receiving study drug or within 30 days of receiving the last dose of 
study drug, even though the event may not appear to be study drug related, must be promptly 
reported (within 24 hours) by telephone, e-mail, or telefax to the sponsor (or designee). 
Emergency Contact Information  
For SAE/SUSAR reporting: 
For any other questions or to 
contact the medical monitor: 
INC Drug Safety 
Fax: (877) 464-7787 	
. 
Email: INCDrugSafety@INCResearch.com  
John L Ryan, PhD, IVID 
Kadmon Corporation 
450 East 29th Street 
New York, NY 10016 
Telephone: 	
Cell: (617) 230-4764 
E-mail: 	
john@kadmon.com  
SAE AND SUSAR CRITERIA 
* A SAE is any untoward medical occurrence that at any dose results in any of the following outcomes, regardless of relationship to study 
drug (see Section 11.3.1, Serious Adverse Events for additional information): 
• • Death 
• 
Life-threatening adverse drug event 
• 
Inpatient hospitalization or prolongation of existing hospitalization 
• 
A persistent or significant disability/incapacity 
• 
A congenital anomaly/birth defect 
• 
An important medical event that may jeopardize the subject and may require medical or surgical intervention to prevent 1 of the 
outcomes listed above. 
** A SUSAR is any untoward and unintended responses to an investigational product related to any dose administered, of which the nature, 
or severity, is not consistent with the applicable product information (see also Section 11.3.2 of this document; Suspected Unexpected 
Serious Adverse Reactions). All suspected adverse reactions related to an investigational medicinal product which occur in the concerned 
study and that are both unexpected and serious are subject to expedited reporting. 
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Confidential and Proprietary 

Date of Signature 
(DD Mmm YYYY) 
Ryan, PhD, 
Ka 	
on Chief Medical Officer 
ICD025 	
IND Number 120787 
Protocol Number 1CD025-211 
SPONSOR SIGNATURE 
I have read and approve this protocol. My signature, in conjunction with the signature of the 
investigator, confirms the agreement of both parties that the clinical study will be conducted in 
accordance with the protocol and all applicable laws and regulations including, but not limited 
to, the International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice 
(GCP), the Code of Federal Regulations (CFR), and the ethical principles that have their origins 
in the Declaration of Helsinki. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
INVESTIGATOR SIGNATURE 
I have read and approve this protocol. My signature, in conjunction with the signature of the 
sponsor, confirms the agreement of both parties that the clinical study will be conducted in 
accordance with the protocol and all applicable laws and regulations including, but not limited 
to, the International Conference on Harmonisation Guideline for Good Clinical Practice (GCP), 
the Code of Federal Regulations (CFR), and the ethical principles that have their origins in the 
Declaration of Helsinki. 
Nothing in this document is intended to limit the authority of a physician to provide emergency 
medical care under applicable regulations. 
Investigator Signature 
Date of Signature 
(DD Mmm YYYY) 
Name of Investigator (please print) 
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Kadmon Corporation 

KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
1 SYNOPSIS 
Study Title 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding 
Study to Evaluate the Safety, Tolerability, and Efficacy of KD025 in Adult 
Subjects with Moderate to Severe Chronic Plaque Psoriasis who are 
Candidates for Systemic Therapy or Phototherapy 
Clinical Phase 
2 
Number of Study Centers 
Up to 20 
Study Background 
Psoriasis is an autoimmune disease that affects many parts of the body but 
is primarily manifested in the skin. It affects 2% to 3% of the population 
of the world, making it a very common inflammatory autoimmune disease. 
The most common form of psoriasis, called psoriasis vulgaris, accounts for 
over 80% of the people with psoriasis. This type of psoriasis appears as 
raised plaques of dry scaly skin that may affect multiple regions of the 
body. Psoriasis is graded as mild, moderate, or severe based on the 
percentage of the body affected and the intensity of the inflammation. 
Several genetic loci have been associated with psoriasis and the major 
genetic determinant, psoriasis susceptibility, accounts for up to 50% of the 
hereditary aspects of the disease. This locus encodes several immune 
functions as well as epidermis-associated proteins that are expressed and 
up-regulated in psoriasis. The genetic basis of sensitivity to psoriasis is 
supported by the fact that there is 70% concordance in identical twins. 
The pathogenesis of psoriasis is not fully understood. However, it has 
been recognized that the recently discovered T helper 17 (Th17) cells, 
which represent highly proinflammatory cells that function in the 
induction of multiple autoimmune diseases as well as enhancing the 
clearance of extracellular pathogens, play a critical role in the pathogenesis 
of psoriasis. Th17 cells secrete interleukins IL-17A, IL-17F, and IL-22, 
which can activate keratinocytes and endothelial cells in the skin. 
Antibodies directed against IL-17 have been approved by the United States 
(US) Regulatory Authorities. Secukinumab is a human 11-17A antagonist 
indicated for the treatment of moderate to severe chronic plaque psoriasis 
in adult patients who are candidates for systemic therapy or phototherapy. 
It is administered subcutaneously and has demonstrated robust efficacy in 
4 well-controlled clinical studies. The primary endpoints for these 
4 studies were the proportion of subjects who achieved a reduction in 
Psoriasis Area and Severity Index (PAST) score of at least 75% (PAST 75) 
from baseline to Week 12 and treatment success (clear or almost clear) on 
the Physician's Global Assessment (PGA; modified 2011). An increase of 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
infections was reported, as well as a few exacerbations of Crohn's disease 
and hypersensitivity. 
Another subcutaneous agent, ustekinumab, has been approved for the same 
indication. Ustekinumab is a human IL-12 and IL-23 antagonist indicated 
for the treatment of adult patients (18 years or older) with moderate to 
severe chronic plaque psoriasis who are candidates for phototherapy or 
systemic therapy. An increase of infections and a few cases of skin cancer 
were reported in 2 large placebo-controlled studies. 
One oral agent, apremilast (an inhibitor of phosphodiesterase 4), has been 
approved for the treatment of adult patients with moderate to severe 
chronic plaque psoriasis who are candidates for phototherapy or systemic 
therapy. However, safety concerns such as depression, weight decrease, 
and issues with drug interactions due to a strong cytochrome P450 enzyme 
induction have been reported. Also, administration requires a titration at 
initiation due to gastrointestinal (GI) side effects. The efficacy at 16 
weeks was relatively less than that observed with secukinumab and 
usteldnumab. In 2 large controlled studies, efficacy results were PAST 75 
of 33.1% and 28.8% versus placebo 5.3% and 5.8%, with the static 
Physician Global Assessment (sPGA) of "clear" or "almost clear" of 
21.7% and 20.4% versus placebo 3.9% and 4.4%. Apremilast is also 
approved for psoriatic arthritis. 
Several Janus kinase (Jak) inhibitors have been studied for the therapy of 
psoriasis as well as other autoimmune diseases. However, none has been 
approved for the treatment of psoriasis to date. Tofacitinib is an inhibitor 
of Jak 3 with somewhat less activity against Jak 1 and Jak 2. It has been 
approved by the Food and Drug Administration (FDA) as a twice daily 
(BID) oral medication for the therapy of rheumatoid arthritis and is 
marketed as XELJANZ®, and has multiple severe infectious and 
immunologic side effects associated with therapy. Monotherapy with 
tofacitinib was associated with a modest increase in American College of 
Rheumatology 20% (ACR20) improvement criteria compared with 
placebo (57% versus 26%). Ruxolitinib is a Jak 1 and Jak 2 inhibitor that 
has been approved for myelofibrosis. It has also been associated with 
severe side effects including bone marrow suppression. Both of the above 
Jak inhibitors have undergone initial clinical testing in psoriasis, but the 
side effect profile of this class of inhibitors has been troublesome. 
Several studies have been perfolined with etanercept and adalimumab, 
both of which block tumor necrosis factor alpha (TNFa) and have 
demonstrated efficacy in the therapy of rheumatoid arthritis, but no 
therapy has been as effective as IL-17 blockade in the therapy of psoriasis. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
A number of biologic products have been approved for the treatment of 
moderate to severe chronic plaque psoriasis. Interestingly, secukinumab, 
an IL-17 targeting agent, has shown robust efficacy with rapid onset. 
However, there are still safety concerns and most of these products are 
parenterally administered. Apremilast, which does not target IL-17, is an 
approved oral agent with an acceptable risk benefit. An oral agent such as 
KD025, which targets TL-17, could potentially provide an oral treatment 
option with an improved safety and efficacy profile. 
Study Rationale 
This proof-of-principle, placebo-controlled study is designed to evaluate 
the safety, tolerability, and efficacy of KD025 administered orally for 
16 weeks to subjects with moderate to severe chronic plaque psoriasis who 
are candidates for systemic therapy or phototherapy. Data collected in this 
study will be used along with data from previous KD025 studies to further 
evaluate the safety, tolerability, and efficacy of KD025. 
Recent studies with KD025 have demonstrated that this molecule has anti-
inflammatory activity mediated by the inhibition of secretion of IL-17 and 
IL-21 by Th17 cells. Since this pathway has emerged as a central 
inflammatory pathway in psoriasis, it is possible that an oral formulation 
(e.g., KD025) could offer significant advantages over other available oral 
formulations. This study will provide safety and efficacy data of the 
therapeutic response to evaluate the risk/benefit of treating plaque 
psoriasis with KD025. 
Study Objective(s) 
Primary objective 
• 
To assess the number of subjects that reach PAST 75 after 
16 weeks of dosing with various regimens of KD025 compared 
with placebo 
Secondary objectives 
• 
To assess changes in absolute PAST scores from baseline to 
Week 16 
• 
To assess the mean percent change in PASI scores from baseline 
to Week 16 
• 
To assess safety and tolerability of KD025 
• 
To assess changes in Physicians Global Assessment (PGA) 
• 
To assess changes in Dermatology Life Quality Index (DLQI) 
• 
To assess changes in PAST scores from baseline to Week 48 for 
subjects receiving 48 weeks of KD025 treatment 
• 
To evaluate the difference in PAST scores between Week 16 and 
Week 48 for subjects receiving KD025 for a total of 48 weeks 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Exploratory objectives 
• 
To evaluate the concentration and changes in IL-17 expression in 
blood, tissue, and other biomarkers in punch biopsy before and 
after 16 weeks of dosing with KD025 
Study Design 
Phase 2, double-blind, randomized, placebo-controlled, dose-finding, 
safety, tolerability, and efficacy study. 
Methodology 
This 
will 
manner 
Study 
During 
for 
All 
week 
the 
Day 
All 
over 
moderate 
systemic 
Institutional 
approved 
inclusion/exclusion 
study will be performed in adult male and female subjects with 
to severe chronic plaque psoriasis who are candidates for 
therapy or phototherapy. Subjects who have signed an 
Review Boards/Independent Ethics Committees (IRBs/IECs) 
informed consent form (ICF) and have met all of the 
criteria will be enrolled. Approximately 110 subjects 
be randomly assigned to each of the 5 dose cohorts in a 1:1:1:1:1 
to achieve 22 evaluable subjects at 16 weeks in each cohort. 
an 
for 
at 
Cohort 1 
22 subjects 
200 mg KD025 once daily (QD) 
Cohort 2 
22 subjects 
200 mg KD025 BID 
Cohort 3 
22 subjects 
400 mg KD025 QD 
Cohort 4 
22 subjects 
600 mg/day KD025 (administered as 
400 mg in the morning and 200 mg in 
the evening) 
Cohort 5 
22 subjects 
Matching placebo BID 
additional 
Subject 
endpoints, 
scheduled 
drug will be orally administered in a double-blind fashion. 
the 16 week, double-blind treatment period, data will be collected 
the evaluation of efficacy of KD025. 
subjects will be given the option to receive KD025 400 mg QD for 
32-weeks in an open-label treatment period (week 16 through 
48). Safety, tolerability, and efficacy of KD025 will be evaluated 
remaining period. 
status (relative to PAST) will be collected at screening, Week 1 
1 (baseline) and, for the evaluation of primary and secondary study 
response will be assessed by PAST, PGA, and DLQI scores 
time points throughout the study. 
subjects will have pharmacod3mamic (PD) blood samples collected 
the course of the study. 
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KDO25 	
lND Number 120787 
Protocol Number KDO25-211 
Subjects will undergo medical history evaluations; physical examinations 
([PEs] including weight measurements); vital sign measurements; adverse 
event (AE) assessments; concomitant medication assessments; blood 
sample collection for hematology, chemistry, coagulation, lipid panel, and 
thyroid-stimulating hormone (TSH), urinalysis; pregnancy testing for 
females of childbearing potential; photography (optional); punch biopsy 
(optional); and electrocardiograms (ECG). 
If a subject discontinues from the study prior to 16 weeks, an Early-
Termination visit will be performed and procedures are to be conducted 
immediately upon discontinuation. 
For all subjects, including those who discontinue from the study 
prematurely, a Follow-Up visit will occur 30 days (± 3 days) after the last 
dose of study drug. 
Approximate Number of 
Subjects 
Approximately 110 subjects (approximately 22 subjects per cohort) 
Approximate Overall 
Duration of Subject 
Participation 
Approximate overall duration will be 56 weeks: 4 weeks for screening, 
16 weeks of double-blind treatment, option for an additional 32 weeks of 
open-label treatment, and 4 weeks of follow-up. 
Diagnosis and Main 
Criteria for Inclusion 
Inclusion Criteria 
To be eligible for participation in the study, each subject must meet all of 
the following criteria: 
1. 	
Adult, between the age of 18 and 65 years 
2. 	
Able to provide written ICF prior to the performance of any study- 
specific procedures 
3. 	
A diagnosis of moderate to severe chronic plaque psoriasis and a 
candidate for systemic therapy or phototherapy 
4. 	
A PAST of?: 12 at screening and prior to the first dose of study drug, 
confirmed at Week 1 (Day 1) 
5. 	
> 10% PAST body surface area involvement at screening and prior to 
the first dose of study drug, confirmed at Week 1 (Day 1) 
6. 	
Willing to avoid tanning devices 	
. 
7. 	
Adequate bone marrow function: 
a. Absolute neutrophil count (ANC) > 1500/mm3  
b. Hemoglobin > 9.0 g/dL 
c. Platelets > 100,000/mm3  
8. 	
Adequate safety laboratory values: 
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KDO25 	
li\ID Number 120787 
Protocol Number KDO25-211 
a. Serum total bilirubin within normal limits (WNL) 
b. Aspartate aminotransferase (AST) and alanine aminotransferase 
(ALT) <2 x upper limit of normal (ULN) 
c. Serum creatinine < 1.5 x ULN 
9. 	
Female subjects of childbearing potential have a negative pregnancy 
test at screening. Females of childbearing potential are defined as 
sexually mature women without prior hysterectomy or those who 
have had any evidence of menses in the past 12 months. However, 
women who have been amenorrheic for 12 or more months are still 
considered to be of childbearing potential if the amenorrhea is 
possibly due to prior chemotherapy, anti-estrogens, or ovarian 
suppression. 
• 
Women of childbearing potential (i.e., menstruating women) must 
have a negative urine pregnancy test (positive urine tests are to be 
confirmed by serum test) documented within the 24-hour period 
prior to the first dose of study drug. 
• 
Sexually active women of childbearing potential enrolled in the 
study must agree to use 2 forms of accepted methods of 
contraception during the course of the study and for 3 months 
after their last dose of study drug. Effective birth control includes 
(a) intrauterine device plus one barrier method; (b) on stable 
doses of hormonal contraception for at least 3 months (e.g., oral, 
injectable, implant, transdermal) plus one barrier method; 
(c) 2 barrier methods. Effective barrier methods are male or 
female condoms, diaphragms, and spermicides (creams or gels 
that contain a chemical to kill sperm); or (d) a vasectomized 
partner. 
10. For male patients who are sexually active and who are partners of 
premenopausal women: agreement to use 2 forms of contraception, as 
in criterion 9, bullet 2c above, during the treatment period and for at 
least 3 months after the last dose of study drug. 
11. Willing to complete all study measurements and assessments in 
compliance with the protocol 
Exclusion Criteria 
Any subj ect who meets any of the following criteria will be ineligible for 
participation in the study: 
1. Non-plaque or drug-induced (e.g., antimalarials, lithium) psoriasis (if 
subject is taking angiotensin II receptor blockers or beta blockers 
doses must be stable for 6 months prior to study entry) 
2. Use of systemic corticosteroid within 12 weeks prior to study entry 
3. Use topical corticosteroids except to the face, groin, or scalp 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
4. Use of methotrexate, retinoids (such as acitretin), or calcineurin 
inhibitors (such as cyclosporine) within 4 weeks prior to study entry 
5. Phototherapy within 4 weeks prior to study entry 
6. Biologic therapies, including antibodies to IL-17, anti-TNFa, 
anti-IL-12 and IL-23, within 3 months prior to study entry 
7. Current use of an inhibitor of inducer of CYP3A4 
8. Active viral, fungal, or bacterial skin infection (other than nail fungal 
infection) 
9. Is a pregnant or lactating woman 
10. History of GI surgery including any bariatric surgery, or any 
GI condition that might interfere with drug absorption 
11. Current participation in another study with an investigational drug or 
within 28 days or 5 half-lives of the investigational drug (whichever 
is longer) of study entry 
12. History or other evidence of severe illness or any other conditions that 
would make the subject, in the opinion of the investigator, unsuitable 
for the study 
13. Has QTc(F) interval (QT interval data corrected using Fridericia's 
formula) of > 450 msec (average of 3 readings) during screening 
14. Regular and/or excessive use of alcohol within the 2 years prior to 
study entry defined as alcohol intake > 14 drinks per week in a man 
or > 7 drinks per week in a woman. Approximately 10 g of alcohol 
equals one "drink" unit. One unit equals 1 ounce of distilled spirits, 
one 12-ounce beer, or one 4-ounce glass of wine. 
15. Exposure to KDO25 within the last 6 months prior to study entry, or 
known allergy/sensitivity to KD025 or any other rho-associated, 
coiled-coil-containing protein kinase (ROCK)-2 inhibitor 
16. History or presence of any of the following: 
a. ALT or AST > 2.0 x the upper limit of normal (ULN) at 
screening. (Subjects with an isolated AST elevation of any 
magnitude, or a ratio of AST:ALT > 1.5 should be 
interviewed regarding use of alcohol, have levels repeated 
and participation in the study should be discussed with the 
medical monitor.) 
b. Renal disease and/or serum creatinine > 1.5 x ULN at 
screening 
Test Article(s) 
KD025 will be provided as 200-mg tablets. Kadmon will provide each 
investigator with adequate supplies of KD025 and placebo. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Dosage and 
Administration 
• 
All 
• 
of finishing 
study drug will be administered orally with a meal or within 5 minutes 
a meal. 
Double-Blind Treatment Period 
Cohort 
No. of 
Subjects 
• 
Dose Regimen 
Cohort 1 
22 subjects 
200 mg KD025 QD (subjects will 
receive 1 KD025 200 mg and 
1 matching placebo tablet in the 
morning and a matching placebo in 
the evening) 
Cohort 2 
22 subjects 
200 mg KD025 BID (subjects will 
receive 1 KD025 200 mg and 
1 matching placebo tablet in the 
morning and KD025 200 mg in the 
evening) 
Cohort 3 
22 subjects 
400 mg KDO25 QD (subjects will 
receive 2 KD025 200 mg tablets in 
the morning and a matching placebo 
in the evening) 
Cohort 4 
22 subjects 
600 mg/day KD025 (subjects will 
receive 2 KD025 200 mg tablets in 
the morning and 1 KD025 200 mg 
tablet in the evening) 
Cohort 5 
22 subjects 
Control (subjects will receive 
2 matching placebo tablets in the 
morning and 1 matching placebo 
tablet in the evening) 
32-Week Open-Label Continuation Period (Week 16 
through Week 48) 
All subjects 
400 mg KD025 QD (subjects will 
receive 2 KD025 200 mg tablets in 
the morning) 
Duration of Treatment 
Up to 48 weeks of treatment: All subjects will receive blinded study drug 
(either KD025 or placebo) from randomization, for a total of 16 weeks. 
Subjects randomized to KD025 or placebo will have the option to continue 
400 mg of KD025 QD treatment for an additional 32 weeks in the open-
label treatment period. 
Concomitant Treatment 
Subjects will be counseled to avoid non-prescribed medicines or 
complementary alternative medicines excluded by the study. Any 
medications a subject receives from signing ICF through the end-of-study 
(30-Day Follow-Up visit) will be documented. 
Subjects may be receiving low-dose oral corticosteroids (< 10 mg daily 
prednisone or equivalent) at study entry. Oral corticosteroid dose must be 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
stable for at least 1 month prior to study entry and expected to remain 
stable throughout participation. Any changes in systemic corticosteroid 
dose will be documented on the electronic Case Report form (eCRF). 
Topical corticosteroids or immunosuppressive therapies to the face, groin, 
or scalp are allowed. Prior systemic treatments, including biologics, are to 
be recorded on the eCRF, including duration of exposure and reason for 
discontinuation. 
Safety Evaluation 
Safety assessments will include AEs, serious adverse events (SAEs), PEs 
(including weight), vital sign measurements (including blood pressure 
[BP], pulse rate, respiratory rate, and temperature), clinical laboratory 
evaluations (hematology, chemistry, urinalysis, coagulation, lipid panel, 
TSH), ECGs, and reasons for treatment discontinuation due to toxicity. 
The AE reporting period for a subject enrolled in the study begins when 
the subject signs the ICF and continues through 30 days after the last dose 
of study drug. All AEs that occur in enrolled subjects during the AE 
reporting period must be reported on subjects' eCRFs, regardless of the 
relationship of the AE to study drug. Any known untoward event that 
occurs beyond the AE reporting period that the investigator assesses as 
possibly related to study drug also should be reported to the sponsor. 
Subjects with ongoing AEs/SAEs will be followed until resolution or a 
new treatment is started. 
Efficacy Evaluation 
The primary efficacy endpoint for analysis will be the number (%) of 
subjects with a 75% decrease in PAST at Week 16. 
The secondary efficacy endpoints for analysis will include the following: 
1. A 50% reduction in Week 16 PAST score (PAST 50) 
2. The mean Week 16 percent change from baseline in PAST 
3. Improvements in PGA of "clear" or "almost clear" at Week 16 
4. Improvements in DLQI at Week 16 
The exploratory efficacy endpoints are: 	
. 
• 
To evaluate the concentration and changes in IL-17 expression 
in blood, tissue, and other biomarkers in punch biopsy after 
16 weeks of dosing with KD025 
Efficacy analyses will be divided into 2 periods: the double-blind 
treatment period through database lock at Week 16, and the 32-week, 
open-label continuation period. 
Pharmacodynamics 
All subjects will have PD blood samples collected over the course of the 
study. Subjects who elect to continue therapy will also have PD blood 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
samples collected. For any subject who discontinues prematurely, blood 
for PD evaluation will also be collected at the Early-Termination visit. 
Samples will be evaluated for the expression of the psoriasis-associated 
cytokine, 1L-17, in plasma. 
Statistical Analysis 
Data Presentations/Descriptive Statistics 
The sample size will be 110 subjects due to early study termination. 
Two populations will be employed in the analysis of study data: 
• 
The modified intent-to-treat (mITT) population will consist of 
all subjects who are randomized and take at least 1 dose of 
study drug. All safety analyses will be performed on the mITT 
population. 
• The Evaluable for Efficacy population will consist of subjects 
who have non-missing baseline and Week 16 PAST scores and 
do not have a major protocol violation. 
Demographics, subject disposition, and screening and baseline 
characteristics will be summarized for mITT populations, where 
appropriate. 
Efficacy analyses will include the number (%) of subjects with a 75% 
decrease in PAST (number of subjects that reach PAST 75) at Week 16 in 
the KD025 treatment groups compared with the placebo group in a 
pairwise manner using a Fisher's exact test. The number of subjects who 
reach PAST 50 at Week 16 will be analyzed similarly. 
Treatment group differences in DLQI and PGA changes from baseline to 
Week 16 will be assessed using an analysis of covariance (ANCOVA) 
model with treatment as a fixed effect and a subject's baseline value as a 
covariate. 
No adjustments for multiplicity are being made for this Phase 2 study. 
The primary safety endpoint will be the percentage of subjects in each 
treatment group experiencing AEs. 
Treatment-emergent AEs (TEAEs) will be summarized by treatment group 
using Medical Dictionary for Regulatory Activities (MedDRA®) System 
Organ Class (SOC) and preferred teun, classified from verbatim terms 
(Version 18.1 or higher). The incidence and percentage of subjects with at 
least 1 occurrence of a preferred term will be included, according to the 
most severe grade using a 5-point scale (mild, moderate, severe, life 
threatening, or death). The number of events per preferred term will also 
be summarized. Causality (relationship to study treatment) will be 
summarized separately. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
AEs, SAEs, related AEs, related SAEs, > Grade 3 AEs, related? Grade 3 
AEs, and AEs leading to withdrawal, or treatment discontinuation will be 
summarized by treatment group according to SOC and preferred terms. 
AEs will also be presented in listings. Duration of AEs will be determined 
and included in listings, along with action taken and outcome. 
Laboratory results will be classified using the Toxicity Grading Scale for 
Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Studies and summarized. Incidence of laboratory abnormalities 
will be summarized by treatment group. The worst on-study grade after 
the first dose of study drug will be summarized by treatment group. The 
incidence of? Grade 3 laboratory abnormalities under treatment and shifts 
in toxicity grading from baseline to highest grade post-baseline will be 
displayed. 
Vital sign measurements will be summarized at each scheduled time point 
using descriptive statistics. 
The exploratory endpoints are to evaluate changes in blood and punch 
biopsy PD markers. 
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IND Number 120787 
Protocol Number KDO25-211 
Table 1-1 	
Schedule of Assessments 
Assessments 
Screening 
Double-Blind Treatment Period 
32-Week Open-Label Continuation Period 
Unscheduled or 
Early 
Termination" 
Visit 
(±3 days) 
30-Day 
Follow- 
Up' 
(±3  
days) 
Week 1 
Week 
4 
Week 
8 
Week 
12 
Week 
16a  
Week 
20 
Week 
24 
Week 
30 
Week 
36 
Week 
42 
Week 
48 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Day 
-28 to -1 
1 
(Baseline) 
28 
(±3 days) 
56 
(±3 days) 
84 
(±3 days) 
112 
(±3 days) 
140 
(±3 days 
168 
(±-3 days) 
210 
(±3 days) 
252 
(±3 days) 
294 
(±3 days) 
336 
(±3 days) 
Informed consent 
X 
Demographics and Medical history 
X 
Physical examination" 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs' 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and serum chemistry' 
Xg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Lipid panel" 
Xg 
X 
X 
X 
X 
X 
X 
X 
X 
PT, PTT, lNR 
Xg 
X 
X 
X 
X 
X 
X 
X 
X 
TSH 
Xg 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
Xg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Supine 12-Lead ECG' 
X 
X 
X 
X 
X 
Pregnancy testi 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization" 
X 
Photographs (optional)' 
X 
X 
X 
X 
X 
Punch Biopsy (optional)tm 
X 
X 
PD whole blood sample" 
X 
X 
X 
X 
X 
X 
Page 16 of 90 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Assessments 
Screening 
Double-Blind Treatment Period 
32-Week Open-Label Continuation Period 
Unscheduled or 
Early 
Terminationb 
Visit 
(±3 days) 
30-Day 
Follow- 
Up' 
(±3 
days) 
Week 1 
Week 
4 
Week 
8 
Week 
12 
Week 
168  
Week 
20 
Week 
24 
Week 
30 
Week 
36 
Week 
42 
Week 
48 
Visit 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
Day 
-28 to -1 
1 
(Baseline) 
28 
(±3 days) 
56 
(t3 days) 
84 
(±3 days) 
- 
112 
(±3 days) 
140 
W days 
168 
W days) 
210 
(±3 days) 
252 
(±3 days) 
294 
(±3 days) 
336 
(±3 days) 
PASI Scoring 
X° 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PGA Scoring 
X 
X 
X 
X 
X 
X 
X 
X 
X 
DLQI 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study drug administration r 
X 
X 
X 
X 
Dispense/Collect study drug Diary  
q 
X 
X 
X 
X 
Concomitant medications 
To be collected from the date that the informed consent form is signed until 30 days after last dose of study drug. 
Adverse events 
DLQI = Dermatology Life Quality Index; ECG = electrocardiogram; INR= international normalized ratio; PASI = Psoriasis Area and Severity Index; PD = pharmacodynamics; 
PGA = Physicians Global Assessment; PT = prothrombin time; PIT = partial thromboplastin time; TSI-I = thyroid-stimulating hormone. 
a. After Week 16 assessments in the double-blind treatment period, subjects will be given the option to receive KD025 400 mg QD for an additional 32-
weeks in an open-label treatment period (end of week 16 assessments through week 48). 
b. Unscheduled visits and the assessments performed are at the investigator's discretion, but may include any or all of those listed. An Early-Termination 
visit will be scheduled for all subjects who discontinue prematurely from study drug during the double-blind or open-label treatment periods and 
procedures are to be conducted immediately upon discontinuation. 
c. For all subjects, including those who discontinue from the study prematurely, a Follow-Up visit should occur 30 days (± 3 days) after their last dose of 
study drug. 
d. Physical examinations will include weight. Height is to be collected only at the Screening visit. 
e. Vital sign measurements will include sitting blood pressure (BP), heart rate, respiratory rate, and temperature after 5 minutes of rest. Refer to 
Section 7.2.4 for appropriate BP measuring technique. 
f. Refer to Section 7.2.5 for a complete list of required hematology and serum chemistry assessments. If increases in liver enzymes are observed at any 
time in a subject, refer to Section 9.4. 
g. If laboratory assessments are done within 14 days of Day 1, they do not need to be repeated on Day 1. 
Kadmon Corporation 
12 Mar 2019 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
h. Lipid panel to include total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol, and low density lipoprotein (LDL) cholesterol. 
i. 
ECGs are to be performed immediately prior to blood sample collection (tolerance window: -240 minutes to 0 hour) and to be obtained in triplicate 
after 5 minutes of resting in the supine position (see Section 7.2.5 for additional information). 
J. 	
Pregnancy tests will be done using urine samples in women of childbearing potential. Subject must have a negative urine pregnancy test documented 
within the 24-hour period prior to the first dose of study drug. Confirm with serum testing if urine sample is positive. 
k. 	
On Day 1 (Week 1), prior to dosing, subjects will be randomized to receive 200 mg KD025 once daily (QD), 200 mg KD025 twice daily (BID), 
400 mg KD025 QD, 600 mg/day KD025, or matching placebo. On Day 112 (Week 16) after all assessments are complete in the double-blind treatment 
period, subjects will be given the option to continue in the 32-week open-label treatment period, during which all participating subjects will receive 
KDO25 400 mg QD for 32weeks. 
I. 	
Photos will be taken of affected area(s) if the subject agrees to them. Detailed instructions will be provided. 
m. Punch biopsies from clear unaffected skin and a selected lesion will be collected predose on Day 1 (Week 1) and from the selected lesion on Day 112 
(Week 16). Subjects have the option to decline the punch biopsy. 
n. PD blood samples to be collected predose and 6 hours postdose on Day 1 of Weeks 1 and 8. PD blood samples to be collected predose on Day 1 of 
Week 16; predose on Day 1 of Week 48 (for those subjects receiving KD025 during the 32-week continuation period), and at the 30-Day Follow-Up 
visit. 
o. To be eligible for the study, subjects must have a PASI of 12 at screening and prior to the first dose of study drug, confirmed at Day 1 (Week 1). 
p. Subjects will take the first dose of study drug in the clinic and at each visit when PD blood samples are collected. Then study drug will be dispensed for 
home administration. Study drug is to be taken with a meal or within 5 minutes of finishing a meal. 
q. Subjects will be required to keep study drug diaries in which they will record the date of study drug administrations. These diaries will be dispensed at 
the Day 1 (Week 1) visit. Final collection will be at Week 16 for those who do not wish to continue into the open-label period. For subjects that 
continue to the open-label treatment period, a new diary will be distributed at the Week 16 visit and will be collected at the Week 48 visit. For subjects 
who discontinue the study prematurely, the diary will be collected at the Early-Termination visit. 
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12 Mar 2019 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
2 TABLE OF CONTENTS 
PROCEDURES IN CASE OF EMERGENCY 	
2 
SPONSOR SIGNATURE 	
3 
INVESTIGATOR SIGNATURE 	
4 
1 SYNOPSIS 5 
2 	
TABLE OF CONTENTS 	
19 
3 	
LIST OF ABBREVIATIONS 	
24 
4 	
BACKGROUND AND RATIONALE 	
26 
4.1 	
Study Rationale 	
28 
4.2 	
Selection of Doses in this Study 	
28 
4.3 	
Previous Clinical Experience with KD025 	
29 
4.4 	
KD025 Nonclinical Toxicology 	
30 
4.5 	
Compliance Statement 	
30 
5 	
STUDY OBJECTIVES 	
32 
5.1 	
Primary Objectives 	
32 
5.2 	
Secondary Objectives 	
32 
5.3 	
Exploratory Objective 	
32 
5.4 	
Study Sites 	
32 
5.5 	
Study Endpoints 	
32 
5.6 	
Overview of Study Design 	
33 
5.7 	
Randomization and Blinding 	
34 
6 	
STUDY POPULATION 	
35 
6.1 	
Target Population 	
35 
6.2 	
Inclusion Criteria 	
35 
6.3 	
Exclusion Criteria 	
37 
7 	
STUDY ASSESSMENTS AND PROCEDURES 	
39 
7.1 	
General Study Procedures 	
39 
7.1.1 	
Screening Enrollment 	
39 
7.1.2 	
Double-Blind Treatment Period 	
39 
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12 Mar 2019 
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KDO25 	
1ND Number 120787 
Protocol Number KDO25-211 
7.2 
7.1.3 	
32-week Open-Label Continuation Period 	
 
7.1.4 	
Early-Termination Visit 	
 
7.1.5 	
Unscheduled Visit 	
 
7.1.6 	
30-day Follow-up Visit 	
 
Description of Study Procedures 	
 
40 
40 
40 
40 
40 
7.2.1 	
Demographics and Medical History 	
 
40 
7.2.2 	
Physical Examination 	
 
41 
7.2.3 	
Vital Sign Measurements 	
 
41 
7.2.4 	
Laboratory Assessments 	
 
41 
7.2.5 	
12-Lead Electrocardiogram 	
 
43 
7.2.6 	
Pregnancy Testing 	
 
43 
7.2.7 	
Randomization 	
 
43 
7.2.8 	
Punch Biopsy (Optional) 	
 
44 
7.2.9 	
Blood Sampling for Pharmacodynamics 	
 
44 
7.2.10 	
Psoriasis Area and Severity Index Scoring 	
 
44 
7.2.11 	
Relative Physician's Global Assessment 	
 
45 
7.2.12 	
Photography (Optional) 	
 
46 
7.2.13 	
Study Drug Administration 	
 
46 
7.2.14 	
Subject Drug Diaries 	
 
46 
7.2.15 	
Adverse Event Assessments 	
 
47 
8 
REMOVING SUBJECTS FROM STUDY 	
 
48 
8.1 
Subject Withdrawal 	
 
48 
8.1.1 	
Treatment Discontinuation 	
 
48 
8.1.2 	
Study Discontinuation 	
 
48 
8.2 
Stopping Rules 	
 
49 
8.2.1 	
Adverse Events Stopping Criteria 	
 
49 
8.2.2 	
Blood Pressure Stopping Criteria 	
 
49 
8.3 
Study Termination 	
 
50 
8.4 
Replacements 	
 
50 
9 
STUDY DRUG 	
 
51 
9.1 
Dose and Schedule of Study Drug and Reference Therapy 	
 
51 
9.2 
32-Week Open-Label KD025 Therapy (Week 16 through Week 48) 	
 
52 
9.3 
Missed Doses 	
 
52 
9.4 
Evaluation of Liver-Related Blood Tests 	
 
52 
9.5 
Identity of Investigational Products 	
 
53 
9.6 
Study Drug Packaging and Labeling 	
 
53 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
9.7 
Dispensing of Study Drug and Dosing Compliance 	
 
54 
9.8 
Study Drug Storage 	
 
54 
9.9 
Study Drug Accountability 	
 
55 
9.10 
Study Drug Handling 	
 
55 
9.10.1 	
Disposition of Used Supplies 	
 
55 
9.10.2 	
Inventory of Unused Supplies 	
 
55 
10 
CONCOMITANT MEDICATION AND TREATMENT 	
 
56 
11 
SAFETY 	
57 
11.1 
Safety Parameters 	
 
57 
11.2 
Adverse Event Definition 	
 
57 
11.3 
Evaluating Adverse Events 	
 
57 
11.3.1 	
Serious Adverse Events 	
 
58 
11.3.2 	
Suspected Unexpected Serious Adverse Reaction 	
 
59 
11.3.3 	
Unexpected Adverse Events 	
 
59 
11.3.4 	
Non-Serious Adverse Events 	
 
59 
11.3.5 	
Protocol-Related Adverse Events 	
 
59 
11.3.6 	
Relationship to Study Drug 	
 
60 
11.3.7 	
Recording Adverse Events 	
 
60 
11.3.8 	
Hospitalization 	
 
60 
11.3.9 	
Serious Adverse Event Reporting 	
 
60 
11.3.10 Laboratory Data 	
 
64 
11.3.11 	
Medication Errors 	
 
64 
11.3.12 Follow-Up of Adverse Events 	
 
64 
12 
STATISTICAL CONSIDERATIONS 	
 
65 
12.1 
General Design 	
 
65 
12.2 
Sample Size Justification 	
 
66 
12.3 
Study Populations 	
 
66 
12.4 
Subject Accountability, Demographics, and Baseline Characteristics 	
 
66 
12.5 
KD025 Exposure 	
 
66 
12.6 
Concomitant Medications 	
 
66 
12.7 
Efficacy Analysis 	
 
66 
12.8 
Safety Data 	
 
67 
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KDO25 	
1ND Number 120787 
Protocol Number KDO25-211 
13 	
DATA QUALITY ASSURANCE 	
69 
14 	
ETHICAL ASPECTS 	
70 
14.1 Local Regulations 	
70 
14.2 Informed Consent Form 	
70 
14.3 Institutional Review Board 	
71 
14.4 Future Use of Subject Samples 	
71 
15 	
CONDITIONS FOR MODIFYING THE PROTOCOL 	
72 
16 	
CONDITIONS FOR TERMINATING THE STUDY 	
73 
17 	
STUDY DOCUMENTATION, CRFS, AND RECORD KEEPING 	 74 
17.1 Investigator's Files and Retention of Documents 	
74 
17.2 Source Documents and Background Data 	
74 
17.3 Audits and Inspections 	
75 
17.4 Electronic Case Report Forms 	
75 
18 MONITORING THE STUDY 	
76 
19 	
CONFIDENTIALITY OF STUDY DOCUMENTS AND SUBJECT RECORDS 	
77 
20 PUBLICATION OF DATA AND PROTECTION OF TRADE SECRETS 	
78 
21 REFERENCES 	
79 
LIST OF TABLES 
Table 1-1 	
Schedule of Assessments 	
16 
Table 5-1: 	
Dosing Cohorts 	
33 
Table 7-1: 	
Clinical Laboratory Panels 	
42 
Table 9-1 	
Dosing Cohorts 	
51 
Table 9-2: 	
Grading of Liver-Related Laboratory Abnormalities 	
53 
Table 9-3 	
Investigational Products 	
53 
List of Appendices 
Appendix A: Tables for Grading Laboratory Abnormalities 	
80 
Appendix B: Correction for Heart Rate (Fridericia)* 	
83 
Appendix C: Relative Physician's Global Assessment 	
84 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Appendix D: Dermatology Life Quality Index 	
85 
Appendix E: Clinical Symptom and Adverse Event Grading Scale 	
87 
Appendix F: Clinical Adverse Events: Determining Relationship to Study Drug 	
88 
Appendix G: CYP3A4Inducersand inhibitors 	
90 
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Confidential and Proprietary 

KDO25 	
lND Number 120787 
Protocol Number KDO25-211 
3 	
LIST OF ABBREVIATIONS 
AE 
adverse event 
ACR20 
American College of Rheumatology 20% 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
ANCOVA 
analysis of covariance 
AST 
aspartate aminotransferase 
ATC 
anatomical therapeutic chemical 
AUC 
area under the curve 
BA/BE 
bioavailability/bioequivalence 
BID 
twice daily 
BP 
blood pressure 
CFR 
Code of Federal Regulations 
Cmax 
maximum plasma concentration 
DLQI 
Dermatology Life Quality Index 
DBP 
diastolic blood pressure 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMEA 
European Medicines Agency 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GGT 
gamma-glutamyl transpeptidase 
HDL 
high density lipoprotein 
HI 
Investigator's Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IGA 
Investigator's Global Assessment 
IND 
Investigation New Drug 
INR 
international normalized ratio 
IRB/TEC 
institutional review board/independent ethics committee 
IRT 
Interactive Response Technology 
Jak 
Janus kinase 
LDL 
low density lipoprotein 
LFT 
liver functions test 
MAD 
multiple ascending dose 
Page 24 of 90 
Confidential and Proprietary 
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Kadmon Corporation 

KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
MedDRA 
Medical Dictionary for Regulatory Activities 
mITT 
modified intent-to-treat 
PASI 
Psoriasis Area and Severity Index 
PD 
phannacodynamics 
PE 
physical examinations 
PGA 
Physician's Global Assessment 
PK 
pharmacokinetics 
PT 
prothrombin time 
PIT 
partial thromboplastin time 
QD 
once daily 
QTc(F) 
QT interval corrected using Fridericia's formula 
ROCK 
Rho-associated, coiled-coil-containing protein kinase 
SAD 
single-ascending dose 	
. 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
sPGA 
static Physician Global Assessment 
SD 
standard deviation 
SUSAR 
suspected unexpected serious adverse reaction 	
. 
SBP 
systolic blood pressure 
TEAR 
treatment-emergent adverse event 
Th17 
T-helper 17 cell 
TID 
three times daily 
TNFa 
tumor necrosis factor alpha 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
US 
United States 
WHO 
World Health Organization 
WNL 
within normal limits 
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12 Mar 2019 
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KDO25 	
lND Number 120787 
Protocol Number KDO25-211 
4 BACKGROUND AND RATIONALE 
Psoriasis is an autoimmune disease that affects many parts of the body but is primarily 
manifested in the skin. It affects 2% to 3% of the population of the world, making it a very 
common inflammatory autoimmune disease. The most common form of psoriasis, called 
psoriasis vulgaris, accounts for over 80% of the people with psoriasis. This type of psoriasis 
appears as raised plaques of dry scaly skin that may affect multiple regions of the body. 
Psoriasis is graded as mild, moderate, or severe based on the percentage of the body affected and 
the intensity of the inflammation. Several genetic loci have been associated with psoriasis and 
the major genetic determinant, psoriasis susceptibility, accounts for up to 50% of the hereditary 
aspects of the disease. This locus encodes several immune functions as well as epidermis-
associated proteins that are expressed and up-regulated in psoriasis. The genetic basis of 
sensitivity to psoriasis is supported by the fact that there is 70% concordance in identical twins. 
The pathogenesis of psoriasis is not fully understood. However, it has been recognized that the 
recently discovered T helper 17 (Th17) cells, which represent highly proinflammatory cells that 
function in the induction of multiple autoimmune diseases as well as enhancing the clearance of 
extracellular pathogens, play a critical role in the pathogenesis of psoriasis. Th17 cells secrete 
IL-17A, IL-17F, and IL-22, which can activate keratinocytes and endothelial cells in the skin. 
Antibodies directed against IL-17 have been approved by United States (US) Regulatory 
Authorities. Secukinumab is a human IL-17A antagonist indicated for the treatment of moderate 
to severe chronic plaque psoriasis in adult patients who are candidates for systemic therapy or 
phototherapy. It is administered subcutaneously and has demonstrated robust efficacy in 4 well-
controlled clinical studies. The primary endpoints for these 4 studies were the proportion of 
subjects who achieved a reduction in Psoriasis Area and Severity Index (PAST) score of at least 
75% (PAST 75) from baseline to Week 12 and treatment success (clear or almost clear) on the 
Physicians Global Assessment (PGA; modified 2011). An increase of infections was reported, 
as well as a few exacerbations of Crohn's disease and hypersensitivity. 
Another subcutaneous agent, ustekinumab, has been approved for the same indication. 
Ustekinumab is a human IL-12 and IL-23 antagonist indicated for the treatment of adult patients 
Page 26 of 90 
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Kadmon Corporation 

KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
(18 years or older) with moderate to severe chronic plaque psoriasis who are candidates for 
phototherapy or systemic therapy. An increase of infections and a few cases of skin cancer were 
reported in 2 large placebo-controlled studies. 
One oral agent, apremilast (an inhibitor of phosphodiesterase 4), has been approved for the 
treatment of adult patients with moderate to severe chronic plaque psoriasis who are candidates 
for phototherapy or systemic therapy. However, safety concerns such as depression, weight 
decrease, and issues with drug interactions due to a strong cytochrome P450 enzyme induction 
have been reported. Also, administration requires a titration at initiation due to gastrointestinal 
(GI) side effects. The efficacy at 16 weeks was relatively less than that observed secukinumab 
and ustekinumab. In 2 large controlled studies, efficacy results were PAST 75 of 33.1% and 
28.8% versus placebo 5.3% and 5.8%, with the static Physician Global Assessment (sPGA) of 
"clear" or "almost clear" of 21.7% and 20.4% versus placebo 3.9% and 4.4%, respectively. 
Apremilast is also approved for psoriatic arthritis. 
Several Janus kinase (Jak) inhibitors have been studied for the therapy of psoriasis as well as 
other autoimmune diseases. However, none has been approved for the treatment of psoriasis to 
date. Tofacitinib is an inhibitor of Jak 3 with somewhat less activity against Jak 1 and Jak 2. It 
has been approved by the Food and Drug Administration (FDA) as a twice daily (BED) oral 
medication for the therapy of rheumatoid arthritis and is marketed as XELJANZ®, and has 
multiple severe infectious and immunologic side effects associated with therapy. Monotherapy 
with tofacitinib was associated with a modest increase in American College of Rheumatology 
20% (ACR20) improvement criteria compared with placebo (57% versus 26%). Ruxolitinib is a 
Jak 1 and Jak 2 inhibitor that has been approved for myelofibrosis. It has also been associated 
with severe side effects including bone marrow suppression. Both of the above Jak inhibitors 
have undergone initial clinical testing in psoriasis, but the side effect profile of this class of 
inhibitors has been troublesome. 
Several studies have been performed with etanercept and adalimumab, both of which block 
tumor necrosis factor alpha (TNFcc) and have demonstrated efficacy in the therapy of rheumatoid 
arthritis, but no therapy has been as effective as IL-17 blockade in the therapy of psoriasis. 
Kadmon Corporation 
12 Mar 2019 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
A number of biologic products have been approved for the treatment of moderate to severe 
chronic plaque psoriasis. Interestingly, secukinumab, an IL-17 targeting agent, has shown robust 
efficacy with rapid onset. However, there are still safety concerns and most of these products are 
parenterally administered. Apremilast, which does not target IL-17, is an approved oral agent 
with an acceptable risk benefit. An oral agent such as KD025, which targets LL-17, could 
potentially provide an oral treatment option with an improved safety and efficacy profile. 
4.1 	
Study Rationale 
This proof-of-principle, placebo-controlled study is designed to evaluate the efficacy, safety, and 
tolerability of KD025 administered orally for 16 weeks to subjects with moderate to severe 
chronic plaque psoriasis who are candidates for systemic therapy or phototherapy. Data 
collected in this study will be used along with data from previous KD025 studies to further 
evaluate the safety, tolerability, and efficacy of KD025. 
Recent studies with KD025 have demonstrated that this molecule has anti-inflammatory activity 
mediated by the inhibition of secretion of IL-17 and IL-21 by Th17 cells. Since this pathway has 
emerged as a central inflammatory pathway in psoriasis, it is possible that an oral formulation 
(e.g., KD025) could offer significant advantages over other available oral foimulations. This 
study will provide safety and efficacy data of the therapeutic response to evaluate the risk/benefit 
of treating plaque psoriasis with KD025. 
4.2 	
Selection of Doses in this Study 
The only Rho kinase inhibitor that has published human dosing data is fasudil. Fasudil is a 
moderately selective kinase inhibitor but in contrast to KD025 has activity against both 
Rho-associated, coiled-coil-containing protein kinase (ROCK1 and ROCK2). The potency of 
fasudil against ROCK2 is similar to KD025. Fasudil has been marketed in Japan for more than 
10 years as an intravenous drug for the prevention of cerebrovascular spasm after stroke. Fasudil 
was also under development for the treatment of chronic angina. In a Phase 2 clinical study in 
the US (Vicari et al, 2005), fasudil was dosed from 20 mg three times a day (TlD) up to 80 mg 
TlD over 8 weeks. At all doses tested, the adverse events (AEs) in the treatment arm were 
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KDO25 	
IN1D Number 120787 
Protocol Number KDO25-211 
reported as no different from placebo. In a separate study to examine endothelial function in 
subjects and healthy subjects (Nohria et al, 2006), fasudil was dosed at 40 mg TID for 30 days. 
The single-ascending dose (SAD)/multiple-ascending dose (MAD) (KDO25-101) and MAD 
(KDO25-102) studies support daily dosing with KD025 and have shown a safety profile that 
allows daily dosing up to 1000 mg per day. In addition, in Study KD025-103, a Phase 1, 
placebo-controlled study examining the safety, tolerability, and pharmacokinetics (PK) of 
500 mg of KD025 administered BID for 28 days in healthy male and post-menopausal female 
subjects for up to 28 days, the regimen was generally well tolerated. 
Phaimacodynamic (PD) studies in these normal healthy subjects have shown biological activity 
in inhibition of secretion of IL-17 and IL-21 by TH-17 cells in ex vivo stimulated peripheral 
blood mononuclear cells at the 120-, 240-, and 320-mg dose levels. Thus, the dosing selected in 
the proposed study (200 mg once daily [QD], 200 mg BID, 400 mg QD, and 600 mg/day) should 
be both safe and at a level at which biological activity has been measured. 
4.3 	
Previous Clinical Experience with KD025 
A Phase 1 fed or fasted study (KD025-105) was conducted to evaluate the food effect as well as 
to further evaluate the safety and PK of a single 500-mg dose of KD025 administered orally to 
fed and fasted healthy males. 
Study results showed approximately a 3-fold higher exposure (maximum serum concentration 
[Cmax] and area under the curve [AUC]) in the fed state compared with the fasted state. There 
were no treatment emergent adverse events (TEAEs) and no treatment-related AEs were reported 
in any subject after receiving KD025 in either the fed or fasted state. There were no clinically 
relevant changes in vital signs, physical examination (PE) findings, or electrocardiogram (ECG) 
parameters. There were no clinically relevant changes and no clinically meaningful trends in 
hematology, chemistry, and urinalysis laboratory results attributable to study drug during this 
study. Plasma concentrations achieved in this study were comparable to plasma levels achieved 
in previous studies at similar dose levels, where breakfast was provided immediately after dose 
administration. These studies support dosing KD025 with food. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
KD025-205 was a Phase 2a, open-label study in 8 adult subjects with moderately severe 
psoriasis vulgaris who have failed first-line therapy. As with the other studies, 200 mg QD 
KD025 administered daily for 28 days was generally safe and well tolerated. 
KD025-206 was a Phase 2a, open-label, dose-finding study in 36 adult subjects with moderately 
severe psoriasis vulgaris who have failed first-line therapy. The study was a 3-month, open-label 
study with 3 cohorts (200 mg BID, 400 mg QD, and 400 mg BID). KD025 was well tolerated in 
all subjects and demonstrated activity as measured by PASI. The only adverse experience was 
related to elevated alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) levels in 
approximately 20% of the subjects. The KD025 400-mg BID group showed the highest 
(Grade 3) elevations. The 400-mg BID dose will not be pursued in future studies. 
The Investigator's Brochure (I) 2015 includes additional nonclinical and clinical information 
about this agent. 
4.4 	
K0025 Nonclinical Toxicology 
KD025 nonclinical toxicology has been characterized in multiple species using a variety of 
dosing regimens. Details are found in the IB 2015. 
4.5 	
Compliance Statement 
This study will be conducted in compliance with Good Clinical Practice (GCP), including 
International Conference on Harmonisation (ICH) Guidelines, and in general, consistent with the 
most recent version of the Declaration of Helsinki. In addition, the investigator agrees to adhere 
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to all applicable local laws and regulatory requirements relevant to the use of new therapeutic 
agents in the countries involved. 
The study is to be conducted in compliance with the protocol. The appropriate Institutional 
Review Boards/Independent Ethics Committees (IRBs/IECs) must approve the protocol and any 
amendments and the subject informed consent font]. (ICF) prior to implementation. 
Freely given written ICF must be obtained from every subject prior to participation in this 
clinical study. The rights, safety, and well-being of participating subjects are the most important 
considerations and should prevail over interests of science and society. 
Study personnel involved in conducting this study will be qualified by education, training, and 
experience to perform their respective task(s). This study will not use the services of study 
personnel where sanctions have been invoked or where there has been scientific misconduct of 
fraud (e.g., loss of medical licensure, debarment). 
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5 STUDY OBJECTIVES 
5.1 	
Primary Objectives 
The primary objective of the study is as follows: 
• To assess the number of subjects that reach PAST 75 after 16 weeks of dosing with 
various regimens of KD025 compared with placebo 
5.2 	
Secondary Objectives 
The following are the secondary objectives of the study: 
• To assess changes in absolute PAST scores from baseline to Week 16 
• To assess the mean percent change in PAST scores from baseline to Week 16 
• To assess safety and tolerability of KDO25 
• To assess changes in PGA 
• To assess changes in DLQI 
• To assess changes in PAST scores from baseline to Week 48 for subjects receiving 
48 weeks of KD025 treatment 
• To evaluate the difference in PAST scores between Week 16 and Week 48 for subjects 
receiving KD025 for a total of 48 weeks 
5.3 Exploratory Objective 
The exploratory objective for the study is as follows: 
• 
To evaluate the concentration and changes in IL-17 expression in blood, tissue, and 
other biomarkers in punch biopsy before and after 16 weeks of dosing with KD025 
5.4 	
Study Sites 
This study will be conducted at approximately 20 sites in the US. 
5.5 	
Study Endpoints 
The primary safety endpoint will be the percentage of subjects in each treatment group 
experiencing AEs. 
The primary efficacy endpoint for analyses will be the number (%) of subjects with a 
75% decrease in PAST by Week 16. 
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The secondary efficacy endpoints for analysis will include the following: 
• A 50% reduction in Week 16 PAST score (PAST 50) 
• The mean Week 16 percent change from baseline in PAST 
• Improvements in PGA of "clear" or "almost clear" at Week 16 
• Improvements in DLQI at Week 16 
The exploratory efficacy endpoint is: 
• To evaluate the concentration and changes in IL-17 expression in blood, tissue, and 
other biomarkers in punch biopsy after 16 weeks of dosing with KD025 
5.6 	
Overview of Study Design 
This will be a Phase 2, double-blind, randomized, placebo-controlled, dose-finding, safety, 
tolerability, and efficacy study. 
This study will be performed in adult male and female subjects with moderate to severe chronic 
plaque psoriasis who are candidates for systemic therapy or phototherapy. Subjects who have 
signed an IRB/IEC-approved ICF and met all of the inclusion/exclusion criteria will be enrolled. 
Approximately 110 subjects will be randomly assigned to each of the 5 dose cohorts in a 
1:1:1:1:1 manner to achieve 22 evaluable patients at 16 weeks in each cohort (Table 5-1). 
Table 5-1: Dosing Cohorts 
Cohort 1 
22 subjects 
200 mg KD025 QD 
Cohort 2 
22 subjects 
200 mg KD025 BID 
Cohort 3 
22 subjects 
400 mg KD025 QD 
Cohort 4 
22 subjects 
600 mg/day KD025 (administered as 400 mg in the morning 
and 200 mg in the evening) 
Cohort 5 
22 subjects 
Matching placebo BID 
Abbreviations: BID = twice daily; QD = once daily 
Study drug will be orally administered in a double-blind fashion. 
During the 16 week, double-blind treatment period, data will be collected for the evaluation of 
efficacy of KD025. 
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All subjects will be given the option to receive KD025 400 mg QD for 32weeks in an open-label 
treatment period. Safety, tolerability, and efficacy of KD025 will be evaluated for the remaining 
period in the study. 
Subject status (relative to PASI) will be collected during the study for the evaluation of primary 
and secondary study endpoints. Response will be assessed by PAST, PGA, and DLQI scores at 
scheduled time points throughout the study. 
All subjects will have PD blood samples collected over the course of the study. 
Subjects will undergo medical history evaluations; PEs (including weight measurements); vital 
sign measurements; AE assessments; concomitant medication assessments; blood sample 
collection for hematology, chemistry, coagulation, lipid panel, and thyroid-stimulating hormone 
(TSH), urinalysis; pregnancy testing for females of childbearing potential; photography 
(optional); punch biopsy (optional); and ECGs. If a subject discontinues from the study prior to 
Week 16, an Early-Termination visit will be performed. All procedures are to be conducted 
immediately upon discontinuation. 
For all subjects, including those who discontinue prematurely from the study, a Follow-Up visit 
will occur 30 days (± 3 days) after the last dose of study drug. 
See Table 1-1 (Schedule of Assessments) for specific assessment time points. 
5.7 	
Randomization and Blinding 
This is a double-blind, randomized study. An Interactive Response Technology (MT) system 
will be used for randomization and drug supply management. 
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6 	
STUDY POPULATION 
6.1 	
Target Population 
Approximately 110 adult male and female subjects (approximately 22 subjects per cohort) will 
participate in the study. Subjects will be eligible for enrollment as defined by the following 
inclusion and exclusion criteria. 
6.2 Inclusion Criteria 
To be eligible for participation in the study, each subject must meet all of the following criteria: 
1. Adult, between the ages of 18 and 65 years 
2. Able to provide written ICF prior to the performance of any study specific procedures 
3. A diagnosis of moderate to severe chronic plaque psoriasis and is a candidate for 
systemic therapy or phototherapy 
4. A PASI of? 12 at screening and prior to the first dose of study drug, confirmed at 
Week 1 (Day 1) 
5. > 10% PAST body surface area involvement at screening and prior to the first dose of 
study drug, confirmed at Week 1 (Day 1) 
6. Willing to avoid tanning devices 
7. Adequate bone marrow function 
a. Absolute neutrophil count (ANC) > 1500/mm3  
b. Hemoglobin > 9.0 g/dL 
c. Platelets > 100,000/mm3  
8. Adequate safety laboratory values 
a. Serum total bilirubin within normal limits (WNL) 
b. AST and ALT <2 x upper limit of normal (ULN) 
c. Serum creatinine < 1.5 x ULN 
9. Female subjects of childbearing potential have a negative pregnancy test at screening. 
Females of childbearing potential are defined as sexually mature women without prior 
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hysterectomy or those who have had any evidence of menses in the past 12 months. 
However, women who have been amenorrheic for 12 or more months are still considered 
to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, 
anti--estrogens, or ovarian suppression. 
• Women of childbearing potential (i.e., menstruating women) must have a negative 
urine pregnancy test (positive urine tests are to be confirmed by serum test) 
documented within the 24-hour period prior to the first dose of study drug. 
• Sexually active women of childbearing potential enrolled in the study must agree to 
use 2 forms of accepted methods of contraception during the course of the study and 
for 3 months after their last dose of study drug. Effective birth control includes 
(a) intrauterine device plus one barrier method; (b) on stable doses of homional 
contraception for at least 3 months (e.g., oral, injectable, implant, transdermal) plus 
one barrier method; (c) 2 barrier methods. Effective barrier methods are male or 
female condoms, diaphragms, and spermicides (creams or gels that contain a 
chemical to kill sperm); or (d) a vasectomized partner. 
10. For male patients who are sexually active and who are partners of premenopausal women: 
agreement to use 2 forms of contraception as in criterion 9, bullet 2c above, during the 
treatment period and for at least 3 months after the last dose of study drug 
11. Willing to complete all study measurements and assessments in compliance with the 
protocol 
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6.3 Exclusion Criteria 
Any subject who meets any of the following criteria will be ineligible for participation in the 
study: 
1. Non-plaque or drug-induced (antimalarials, lithium) psoriasis (if subject is taking 
angiotensin II receptor blockers or beta blockers, doses must be stable for 6 months prior 
to study entry) 
2. Use of systemic corticosteroid within 12 weeks prior to study entry 
3. Use topical corticosteroids except to the face, groin, or scalp 
4. Use of methotrexate, retinoids (such as acitretin), or calcineurin inhibitors (such as 
cyclosporine) within 4 weeks prior to study entry 
5. Phototherapy within 4 weeks prior to study entry 
6. Biologic therapies, including antibodies to IL-17, anti-TNFa, anti-IL-12 and IL-23, 
within 3 months prior to study entry 
7. Current use of an inhibitor, inducer, or CYP3A4 (see Appendix G) 
8. Active viral, fungal, or bacterial skin infection (other than nail fungal infection) 
9. Is a pregnant or lactating woman 
10. History of GI surgery including any bariatric surgery, or any GI condition that might 
interfere with drug absorption 
11. Current participation in another study with an investigational drug or within 28 days or 
5 half-lives of the investigational drug (whichever is longer) of study entry 
12. History or other evidence of severe illness or any other conditions that would make the 
subject, in the opinion of the investigator, unsuitable for the study 
13. Has QTc(F) interval (QT interval data corrected using Fridericia's formula) of 
> 450 msec (average of 3 readings) during screening (Appendix B) 
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14. Regular and/or excessive use of alcohol within the 2 years prior to study entry defined as 
alcohol intake > 14 drinks per week in a man or > 7 drinks per week in a woman. 
Approximately 10 g of alcohol equals one "drink" unit. One unit equals 1 ounce of 
distilled spirits, one 12-ounce beer, or one 4-ounce glass of wine. 
15. Exposure to KD025 within the last 6 months prior to study entry, or known 
allergy/sensitivity to KD025 or any other ROCK-2 inhibitor 
16. History or presence of any of the following: 
a. ALT or AST > 2.0 x ULN at screening. (Subjects with an isolated AST elevation 
of any magnitude, or a ratio of AST:ALT > 1.5 should be interviewed regarding 
use of alcohol, have levels repeated and participation in the study should be 
discussed with the medical monitor.) 
b. Renal disease and/or serum creatinine > 1.5 x ULN at screening 
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7 	
STUDY ASSESSMENTS AND PROCEDURES 
Screening assessments outlined in this section and in Table 1-1 will be performed after obtaining 
a signed ICF. 
The timing for these study assessments is presented in Table 1-1 while a listing of clinical 
laboratory parameters to be measured is presented in Table 7-1. 
7.1 	
General Study Procedures 
A description for each phase of the study is provided in this section. 
Confirmation that the most current MB/IEC-approved ICF has been signed should occur before 
any study-specific procedures are perfolined. All subjects who are enrolled and receive KD025 
or undergo study-specific procedures should be re-consented with any updated versions of 
IRB/IEC-approved ICFs during study participation as applicable and per institutional guidelines. 
7.1.1 Screening Enrollment 
Informed consent must be obtained before completing any study-specific procedures. 
After written informed consent has been obtained, subjects will be screened to assess eligibility 
for study participation. All screening assessments are to be performed within 28 days prior to 
first study drug dose, unless otherwise specified. 
If significant changes from baseline are noted during the course of the study, additional 
unscheduled clinic visits may be undertaken by the investigator, or requested by the sponsor, in 
order to determine both the relevance of the finding(s) and the duration of the event(s). 
Subjects who meet the eligibility criteria will be eligible to be enrolled in the study. 
7.1.2 Double-Blind Treatment Period 
Study Day 1 is defined as the date the subject takes the first dose of study drug, with subsequent 
visits numbered sequentially thereafter. Subjects satisfying eligibility requirements will be 
enrolled and should receive the first dose of study drug on Day 1 of the study. 
Procedures will be completed during the treatment period from Week 1 to Week 16 at the times 
designated in the Schedule of Assessments (Table 1-1). 
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7.1.3 32-week Open-Label Continuation Period 
Procedures will be completed during the 32-week continuation period from Week 16 (after the 
completion of assessments in the double-blind treatment period) to Week 48 at the times 
designated in the Schedule of Assessments (Table 1-1). 
7.1.4 Early-Termination Visit 
An Early-Termination visit will be scheduled for all subjects who discontinue prematurely from 
the study during the double-blind or open-label treatment periods and procedures are to be 
conducted immediately upon discontinuation (refer to Table 1-1). 
7.1.5 Unscheduled Visit 
Unscheduled visits and the assessments performed at those visits are at the investigator's 
discretion, but may include any or all of those listed in Table 1-1. 
7.1.6 30-day Follow-up Visit 
Approximately 30 days (± 3 days) after the subjects last dose of study drug, all subjects will 
complete a 30-day Follow-Up visit (Table 1-1). 
7.2 	
Description of Study Procedures 
Refer to Table 1-1 for an outline of the procedures required at each study visit. Informed Consent 
Form. 
All subjects must take part in the ICF process. Adequate time must be allowed for the subject to 
ask questions and make a voluntary decision. No protocol-specific procedures, including 
screening procedures, are to be performed until the subject has signed and dated an 
IRB/TF,C-approved ICF. 
7.2.1 Demographics and Medical History 
A complete medical history will include demographic information, prior medical illnesses and 
conditions, and surgical procedures. 
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7.2.2 Physical Examination 
Physical examinations (PE) will include assessment of skeletal (i.e., muscle aches), neurological 
(i.e., gait) systems, height (screening only) and weight. All procedures will be performed by a 
physician or staff member who is qualified to perform such examinations (e.g., physician's 
assistant, nurse practitioner). 
Any abnormal or clinically significant findings from the PE must be recorded in the appropriate 
electronic case report form (eCRF). 
7.2.3 Vital Sign Measurements 
Vital sign measurements will be collected after the subject has been sitting for 5 minutes. Vital 
sign assessments will include measurements of a sitting BP (mmHg), heart rate (beats per 
minute), respiratory rate (breaths per minute), and temperature (Fahrenheit). 
Note that BP measurements are to be performed using appropriate technique (per guidelines of 
the American Heart Association). Subjects must be seated quietly for at least 5 minutes in a 
chair with their backs supported, feet flat on floor (legs uncrossed), and arms bared on a hard 
surface, with the arm slightly abducted and bent, with palm up and the midpoint of upper arm at 
heart level. Correct cuff and bladder size should be utilized. Two or more readings separated by 
1 to 2 minutes should be averaged. If the first 2 readings differ by more than 5 mmHg, 
additional readings should be obtained and averaged. Record cuff size, arm used, and subject's 
position (if not seated). 
7.2.4 Laboratory Assessments 
A central laboratory will analyze hematology, serum chemistry, coagulation, lipid panel, TSH, 
urinalysis, and biomarker tests. The results will be provided to the investigator (Table 7-1). 
Blood and urine samples for hematology, serum chemistry, coagulation, lipid panel, TSH, 
antibody, and urinalysis will be obtained using standard procedures. 
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Table 7-1: 	
Clinical Laboratory Panels 
Hematology 	
Serum Chemistry 	
Urinalysis 
• 
white blood cell count with 
differential (including at 
minimum: neutrophils, 
basophils, eosinophils, 
lymphocytes, monocytes) 
• 
red blood cell count 
• 
hemoglobin 
• 
hematocrit 
• 
platelet count 
• 
MCV 
• 
albumin 
• 
alkaline phosphatase 
• 
ALT 
• 
AST 
• 
BUN 
• 
calcium 
• 
carbon dioxide 
• 
chloride 
• 
cholesterol 
• 
creatinine 
• 
CPK 
• 
direct bilirubin 
• 
GGT 
• 
globulin 
• 
glucose 
• 
lactate dehydrogenase 
• 
magnesium 
• 
phosphorus 
• 
potassium 
• 
sodium 
• 
total bilirubin 
• 
total protein 
• 
uric acid 
• 
appearance 
• 
color 
• 
pH 
• 
specific gravity 
• 
ketones 
• 
protein 
• 
glucose 
• 
bilirubin 
• 
nitrite 
• 
urobilinogen 
• 
occult blood (microscopic 
examination of sediment will 
be performed only if the 
results of the urinalysis 
dipstick evaluation are 
positive) 
Coagulation 
Thyroid 
• 
lNR. 
• 
PT 
• 
PTT 
• 
TSH 
Lipid Panel 	
Biomarkers 
• 
Total cholesterol 	• M-17 
• 
Triglycerides 
• 
HDL cholesterol 
• 
LDL cholesterol 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; BUN = blood urea nitrogen; CPK = creatine 
phosphokinase; GGT = gamma glutamyl transpeptidase; HDL= high density lipoprotein; INR = international 
normalized ratio; LDL = low density lipoprotein; MCV = mean corpuscular volume; PT = prothrombin time; PTT = 
partial thromboplastin time; TSH = thyroid-stimulating hormone 
Abnormalities in clinical laboratory tests that lead to a change in subject management (e.g., dose 
delay, discontinuation, requirement for additional medication or monitoring) are considered 
clinically significant for the purposes of this study, and will be recorded on the AE eCRF page. 
With the exception of LFTs, laboratory results will be classified using the Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Studies (see Appendix A). Laboratory results for ALT, AST, alkaline phosphatase, GGT, and 
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bilirubin will be classified according to Table 9-2 in Section 9.4. If laboratory values constitute 
part of an event that meets criteria defining it as serious, the event (and associated laboratory 
values) must be reported as an SAE (see Section 11.3.1). 
7.2.5 12-Lead Electrocardiogram 
Supine 12-lead ECGs will be obtained prior to blood sample collection (tolerance window: -240 
minutes to 0 hour). 
Digital 12-lead ECG measurements are to be taken with the subject in a supine position and 
having rested in this position for at least 5 minutes before each reading. The ECG is to be 
repeated 3 times consecutively within 30 minutes (with a required interval of at least 1 to 
2 minutes between ECGs). At each visit, and when possible, the ECG is to be performed 
immediately prior to any blood sample collection. 
The following ECG parameters will be collected: PR interval, RR interval, QRS interval, QT 
interval, and QTc interval (QTc[F]; Fridericia's correction, see Appendix B for formula). The 
ECG findings will be evaluated by a qualified physician for the presence of abnormalities 
(qualitative assessment). The physician will assess each ECG as normal, abnormal/not clinically 
significant, or abnormal/clinically significant. 
Abnormalities in the ECG that lead to a change in subject management (e.g., dose interruption or 
delay, requirement for additional medication or monitoring) or result in clinical signs and 
symptoms are considered clinically significant for the purposes of this study and will be recorded 
on the AE eCRF. If ECG abnormalities meet criteria defining them as serious, they must be 
reported as an SAE (see Section 11.3.1). 
7.2.6 Pregnancy Testing 
Urine pregnancy tests will be collected for women of childbearing potential. Positive results will 
be confirmed with serum testing. 
7.2.7 Randomization 
Following the completion of screening assessments, eligible, consenting subjects will be 
randomized to 1 of 5 dose cohorts. See Section 5.7 for further details. 
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7.2.8 Punch Biopsy (Optional) 
Punch biopsies will be obtained from at least 75% of the subjects. Subjects have the option to 
decline the punch biopsy. Punch biopsies will be taken from clear unaffected skin and a selected 
lesion will be collected predose on Day 1 (Week 1) and from the selected lesion on Day 112 
(Week 16). Biopsies will be obtained through a standard punch biopsy procedure. These 
biopsies will be analyzed for PD markers associated with psoriasis and with Rho Kinase 
inhibition. 
7.2.9 Blood Sampling for Pharmacodynamics 
Blood sample collection for PD will be performed at all sites (refer to Table 1-1 for time points). 
All subjects will have PD blood samples collected over the course of the study. Subjects who 
elect to continue therapy will also have PD blood samples collected. 
For any subject who discontinues prematurely, blood for PD evaluation will be collected at the 
Early Termination visit. 
Samples will be evaluated for the expression of the psoriasis-associated cytokine, IL-17, in 
plasma. Detailed instructions for sample collection and preparation will be provided in a separate 
manual. 
7.2.10 Psoriasis Area and Severity Index Scoring 
• The PAST is a measure of the psoriasis disease severity using the average redness, thickness, and 
scaliness of the lesions (each graded on a 0-4 scale), weighted by the area of involvement 
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(Wozel eta!, 2005). PAST combines the assessment of the severity of lesions and the area 
affected into a single score in the range 0 (no disease) to 72 (maximal disease). 
To score the PAST, the body is divided into 4 sections 
• head (Id): 10% of a person's skin 
• arms (A): 20%) of a person's skin 
• trunk (T): 30%) of a person's skin 
• legs (L): 40% of a person's skin 
Each of these areas is scored by itself, and then the 4 scores are combined into the final PAST. 
For each section, the percent of area of skin involved, is estimated and then transformed into a 
grade from 0 to 6: 
• Grade 0: 0% of involved area 
• Grade 1: <10% of involved area 
• Grade 2: 10%-29% of involved area 
• Grade 3: 30%-49% of involved area 
• Grade 4: 50%-69% of involved area 
• Grade 5: 70%-89% of involved area 
• Grade 6: 90%-100% of involved area 
Within each area, the severity is estimated by 3 clinical signs: erythema (redness), induration 
(thickness), and desquamation (scaling). Severity parameters are measured on a scale of 0 to 4, 
from none to maximum. 
The sum of all 3 severity parameters is then calculated for each section of skin, multiplied by the 
area score for that area and multiplied by weight of respective section (0.1 for head, 0.2 for arms, 
0.3 for body, and 0.4 for legs). 
7.2.11 Relative Physician's Global Assessment 
The relative PGA documents the physician's assessment of the subject's psoriasis status 
(Robinson 2012). Consideration should be given to the percent of body involvement as well as 
overall induration, scaling, and erythema (refer to Appendix C). 
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' 
The DLQI is a skin disease-specific instrument designed to assess the impact of the disease on a 
subject's quality of life (Finlay et al, 1994). Refer to Appendix D for the complete 
questionnaire. 
7.2.12 Photography (Optional) 
Subjects have the option to participate in the photography of selected lesions. The same lesions 
should be photographed throughout the study. Further information can be found in the Kadmon 
photography manual. 
7.2.13 Study Drug Administration 
Subjects will receive an adequate supply of study drug for the intervals between the visits 
scheduled for study drug administration. During the double-blind treatment period, study drug 
will be dispensed in a blinded fashion and each subject will receive 2 tablets to take each 
morning and 1 tablet to take each evening. During the 32-week continuation period, all subjects 
will receive open-label 400 mg KD025 QD, as two 200 mg tablets to be taken in the morning. 
At each designated visit, subjects will receive the morning dose (2 tablets) of study drug in the 
clinic. Subjects will self-administer the balance of daily doses of study drug at home. 
Each dose of study drug should be taken together with a meal or within 5 minutes of finishing a 
meal. See Section 9.1 for further infounation regarding the dosing schedule and Section 9.3 for 
guidance regarding missed doses. 
7.2.14 Subject Drug Diaries 
Subjects will be required to keep study drug diaries in which they will record the date of study 
drug administrations. These diaries will be dispensed at the Day 1 (Week 1) visit. Final 
collection will be at Week 16 for those who do not wish to continue into the open-label period. 
For subjects that complete the open-label treatment period the diary will be collected at the Week 
48 visit. For subjects who discontinue the study prematurely, the diary will be collected at the 
Early-Termination visit. Prior and Concomitant Medications 
All concomitant medications, including corticosteroids and changes in corticosteroid usage 
during the study, will be collected from the time the subject signs the ICF throughout the 
subject's participation in the study. 
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7.2.15 Adverse Event Assessments 
Information regarding the occurrence of AEs will be collected from the time subjects sign the 
ICF throughout their participation in the study, including a period of 30 days after last dose of 
study drug. 
Note: AEs resulting in a subject's peiiiianent discontinuation from the study, 
regardless of seriousness or relationship to study drug, MUST be 
promptly reported to the sponsor. 
See Section 8.2 for stopping rules for this study. Also, if significant increases (>2 x ULN of 
ALT or AST) in liver enzymes are observed at any time, refer to Section 9.4 for additional 
information and recommended procedures. 
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8 REMOVING SUBJECTS FROM STUDY 
Every reasonable effort will be made to keep the subject in the study; however, in the event that 
a subject is withdrawn from the study, every effort will be made by the investigator to complete 
and report the reasons for withdrawal as thoroughly as possible. This evaluation should include 
final observations, as required by the protocol at the time of the subject's withdrawal. The 
reason(s) for termination must be clearly documented on the appropriate page of the eCRF. A 
termination eCRF must be completed for any subject who is enrolled in the study. 
8.1 	
Subject Withdrawal 
A subject's participation in the study may be discontinued for any of the following reasons: 
8.1.1 Treatment Discontinuation 
• An AE requires permanent discontinuation of study drug 
• Voluntary withdrawal by subject 
• Noncompliance to protocol 
8.1.2 Study Discontinuation 
In the event of premature discontinuation, every effort should be made to have the subject come 
to the clinic for an Early-Teunination and 30-day Follow-Up visit in order for the investigator to 
collect all clinical and laboratory data as scheduled. (Refer to Table 1-1, Schedule of 
Assessments for a complete list of procedures to be performed.) If a subject dies, Kadmon will 
actively seek to know the date of death. 
Subjects who are withdrawn from this study due to toxicity are to be followed until: 
• Resolution or stabilization of toxicity 
• The subject is lost to follow-up 
• The event is otherwise explained 
If there is an ongoing toxicity due to KD025, subjects must be followed with appropriate medical 
management until resolution or stabilization. 
A reasonable effort should be made to contact any subject lost to follow-up during the course of 
the study in order to complete assessments and retrieve any outstanding data. If the subjects are 
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unreachable by telephone after 3 attempts, a certified registered return receipt letter should be 
sent requesting that contact be made with the investigator to report updated infoiniation. 
8.2 	
Stopping Rules 
Stopping criteria will be assessed using the Clinical Symptom Adverse Event Grading scale 
(Appendix E) and will include clinically significant changes with respect to BP, dyspepsia, 
nausea or vomiting, or other treatment-emergent AEs that are Grade 2 (moderate) or higher. 
8.2.1 Adverse Events Stopping Criteria 
• AEs of clinical concern 
• Grade 2 (moderate) or higher TEAEs that are determined by the investigator to be 
possibly, probably, or definitely related to study drug (with the exception of 
liver-related adverse events, see Section 9.4); 
• Clinically significant elevation of ALT or AST. See Section 9.4 for risk management 
of LFTs changes observed during the study. 
8.2.2 Blood Pressure Stopping Criteria 
BP is to be measured with the subject in a sitting position according to the guidelines in 
Section 7.2.4. BP measurements meeting stopping criteria should be repeated once, to confirm 
the measurement. The repeat measurement will be used to determine whether the subject meets 
the stopping criteria. 
Clinically significant BP decreases will be defined as follows: 
• An absolute systolic BP (SBP) < 85 mmHg at any time point, or a decrease 
> 30 mmHg in SBP from baseline with accompanying symptoms of hypotension at 
any time point, or an asymptomatic decrease > 30 mmHg from baseline on any 
2 consecutive time points 
OR 
• An absolute diastolic BP (DBP) <45 mmHg at any time point, or a decrease 
>20 mmHg in DBP from baseline with accompanying symptoms of hypotension at 
any time point, or an asymptomatic decrease > 20 mmHg in DBP from baseline on 
2 consecutive time points. 
Clinically significant BP increases are defined as: 
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• An absolute SBP > 180 mmHg at any time point, or an increase > 30 mmHg in SBP 
from baseline with accompanying symptoms of hypertension at any time point, or an 
asymptomatic increase > 30 mmHg from baseline on any 2 consecutive time points 
OR 
• An absolute DBP > 110 mmHg at any time point, or an increase >20 mmHg in DBP 
from baseline with accompanying symptoms of hypertension at any time point, or an 
asymptomatic increase > 20 mmHg in DBP from baseline on 2 consecutive time 
points. 
8.3 	
Study Termination 
Kadmon Corporation has the right to terminate or to stop the study at any time. Reasons for 
study discontinuation may include, but are not limited to the following: 
• The incidence or severity of AEs in this or other related studies indicates a potential 
health hazard to subjects 
• Subject enrollment is unsatisfactory 
• Drug supply issues 
• Data recording is inaccurate or incomplete 
• Excessive subject self-withdrawal 
• Significant protocol violations (e.g., violation of eligibility criteria, dosing errors, 
missing data for study endpoint analysis) 
8.4 Replacements 
Subjects withdrawn from the study prior to receiving any study drug will be replaced by 
enrolling additional subjects into the study. 
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9 	
STUDY DRUG 
9.1 	
Dose and Schedule of Study Drug and Reference Therapy 
After the completion and review of all screening and baseline procedures, eligible, consenting 
subjects will be randomly assigned to 1 of 5 dose cohorts in a 1:1:1:1:1 manner (see Table 9-1). 
Study drug will be orally administered in a double-blind fashion for 16 weeks. 
Study drug will he dispensed by the site pharmacist, or designee. KD025 will be supplied as 
200-mg tablets. Doses to be studied are 200 mg KDO25 QD, 200 mg KD025 BID, 400 mg 
KD025 QD, and KD025 600 mg/day (administered as 400 mg in the morning and 200 mg in the 
evening). Placebo will be supplied as matching tablets. 
Table 9-1 	
Dosing Cohorts 
Cohort 
No. of 
Subjects 
Dose Regimen 
Cohort 1 
22 subjects 
200 mg KD025 QD (subjects will receive 
1 KD025 200 mg and 1 matching placebo 
tablet in the morning and a matching placebo 
in the evening) 
Cohort 2 
22 subjects 
200 mg KD025 BID (subjects will receive 
1 KD025 200 mg and 1 matching placebo 
tablet in the morning and KD025 200 mg in the 
evening) 
Cohort 3 
22 subjects 
400 mg KD025 QD (subjects will receive 
2 KD025 200 mg tablets in the morning and a 
matching placebo in the evening) 
Cohort 4 
22 subjects 
600 mg/day KD025 (subjects will receive 
2 1CD025 200 mg tablets in the morning and 
1 KD025 200 mg in the evening) 
Cohort 5 
22 subjects 
Control (subjects will receive 2 matching 
placebo tablets in the morning and 1 matching 
placebo tablet in the evening) 
Each dose of study drug should be taken together with a meal or within 5 minutes of finishing a 
meal. 
Subjects will return to the clinic as outlined in the Schedule of Assessments (Table 1-1), and will 
receive the morning dose of study drug (2 tablets) during visits when PD samples are to be 
drawn. Subjects will self-administer the balance of daily doses of study drug at home. 
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9.2 	
32-Week Open-Label KD025 Therapy (Week 16 through Week 48) 
Subjects randomized to KD025 or placebo will have the option to continue 400 mg of KD025 
QD treatment for an additional 32 weeks in the open-label treatment period. 
9.3 	
Missed Doses 
• Subjects should make every effort to take the study drug at the same scheduled times 
daily, morning and evening. In the event that the subject misses the planned dose of 
study drug, the following protocol should be followed: If less than 6 hours of time 
have elapsed after the scheduled dose, the drug should be taken and the subject 
should resume their dosing schedule with the next dose. 
• If more than 6 hours of time have elapsed after the scheduled dose, the dose should be 
skipped. The subject should resume the regular planned dosing schedule. 
If the subject skips more than 7 consecutive days of drug, the subject should be discontinued 
from the study. If the subject cannot take KD025 for more than 7 consecutive days due to a 
toxicity, the subject is allowed to re-start study drug. 
9.4 	
Evaluation of Liver-Related Blood Tests 
Clinically significant elevations of liver-related blood tests as defined below require immediate 
drug termination. 
1. ALT or AST > 5 xULN 
2. ALT or AST > 3 xULN and (total bilirubin > 2 xULN or DNR >1.5) 
3. ALT or AST > 3 xULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%) 
4. If the total bilirubin is >2 xULN then obtain direct bilirubin 
If ALT or AST > 2.0 xULN, the subject should remain on study drug with close observation 
which includes: 
1. Repeating liver enzyme, every 48 to 72 hours 
(Frequency of retesting can decrease to once a week or less if abnormalities stabilize or 
the study drug has been discontinued and the subject is asymptomatic.) 
2. Obtaining a more detailed history of symptoms and prior or concurrent diseases 
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3. Obtaining a history of concomitant drug use (including nonprescription medications and 
herbal and dietary supplement preparations), alcohol use, recreational drug use, and 
special diets 
4. Ruling out acute viral hepatitis types A, B, and C 
5. Obtaining a history of exposure to environmental chemical agents 
Table 9-2: 	
Grading of Liver-Related Laboratory Abnormalities 
FEATURE 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ALT 
<1.25 ULN 
1.25-2.5 ULN 
>2.5-5.0 ULN 
>5.0-10 ULN 
>10 ULN 
AST 
<1.25 ULN 
1.25-2.5 ULN 
>2.5-5.0 ULN 
>5.0-10 ULN 
>10 ULN 
Alkaline 
Phosphatase 
<1.25 ULN 
1.25-2.5 ULN 
>2.5-5.0 ULN 
>5.0-10 ULN 
>10 ULN 
GGT 
<1.25 ULN 
1.25-2.5 ULN 
>2.5-5.0 ULN 
>5.0-10 ULN 
>10 ULN 
Bilirubin 
Normal 
>1.0-1.5 ULN 
>1.5-2.5 ULN 
>2.5-5 ULN 
>5 ULN 
Abstracted from: CDER-PHRMA-AASLD Conference 2000, Dufour 2000a and Dufour 2000b. 
Note: A Grade 2 elevation of ALT, for example, does not connote a Grade 2 TEAE and the 
above evaluation should guide stopping rules. 
For further details, see JEB 2015, Summary of Data and Guidance for the Investigator. 
9.5 	
Identity of Investigational Products 
Table 9-3 	
Investigational Products 
Product 
Strength 
Dosage Form 
Route 
 
KD025 
200 mg 
Yellow to pale yellow oval shaped 
tablet 
Oral 
Placebo 
Yellow to pale yellow oval shaped 
tablet 
Oral 
KD025 and placebo will be supplied by Kadmon. 
9.6 	
Study Drug Packaging and Labeling 
KD025 and placebo will be packaged and labeled by the sponsor or designee. The label attached 
to each bottle will provide the following information: 
• Description of contents (number and strength of tablets) and route of administration 
• Directions for use 
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• Storage conditions 
• Product identification code 
• Lot number identification 
• Bottle number 
• Name of protocol sponsor 
• The statement, "Caution: New Drug — Limited by Federal Law to Investigational 
Use" 
• The statement, "Keep out of the reach of children and pets" 
9.7 	
Dispensing of Study Drug and Dosing Compliance 
The amount of study drug dispensed to the subject at the beginning of each dosing month should 
be sufficient to allow for 1 month of dosing. In the 32-week continuation period, the amount of 
KD025 dispensed at each visit will be sufficient to allow for dosing until the next visit. 
The investigator (or designee) will be responsible for recording this information on the 
appropriate study drug inventory. This inventory will be maintained throughout the duration of 
the study and will be periodically reviewed by a representative of the sponsor. 
The investigator (or designee) will instruct the subject that all dispensed bottles must be returned 
at each follow-up visit, at which time a tablet count will be conducted to assure subject dosing 
compliance. 
Additionally, subjects will be required to keep study drug diaries in which they will record the 
details of study drug administrations. These diaries will be dispensed and/or collected according 
to the Schedule of Assessments (Table 1-1). 
9.8 	
Study Drug Storage 
All supplies of study drug are to be stored at United States Pharmacopeia controlled room 
temperature of 20°C to 25°C (66°F to 77°F) with excursions pelinitted between 15°C and 30°C 
(59°F and 86°F). At the clinic, the study drugs are to be stored in a securely locked area, 
accessible to authorized persons only, until needed for dosing. 
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9.9 	
Study Drug Accountability 
The US FDA and other regulatory agencies require accounting for the disposition of all 
investigational drugs received by each clinical site. Information on drug disposition required by 
law consists of the date received, date administered, quantity administered, and the subject to 
whom the drug was administered. The principal investigator is responsible for the accounting 
for all unused study drugs and all used study drug containers. The investigator must maintain a 
complete and current dispensing and inventory record that has been supplied by the sponsor. 
9.10 Study Drug Handling 
At the termination of the study, a final drug accountability review and reconciliation must be 
completed and any discrepancies must be investigated and their resolution documented. 
9.10.1 Disposition of Used Supplies 
At the completion of a subject's participation in the study, all partially used and empty pill 
bottles must be returned to the investigator (or designee) so that a final subject-dosing inventory 
may be conducted. This information will be recorded on the Drug Dispensing Log. 
9.10.2 Inventory of Unused Supplies 
Periodically throughout and at the conclusion of the study, an inventory of unused bottles of 
study drug will be conducted by a representative of the sponsor. 
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10 CONCOMITANT MEDICATION AND TREATMENT 
Subjects will be counseled to avoid non-prescribed medicines or complementary alternative 
medicines excluded by the study. Any medications a subject receives from signing ICF through 
the end of study (30-Day Follow-Up visit) will be documented. After discontinuation of study 
drug, any concomitant medication used in response to an AE is to be recorded on the appropriate 
eCRF. 
Administration of acid-reducing medications should be avoided during the study as these agents 
may decrease exposure to KD025. If acid-reducing agents are needed, H-2 antagonists or 
antacids will be recommended rather than proton pump inhibitors. Administration of 
acid-reducing agents such as H-2 antagonists or antacids, if required, should take place no less 
than 2 hours before or after dosing with KD025. 
Subjects may be receiving low-dose oral corticosteroids (< 10 mg daily prednisone or 
equivalent) at study entry. Oral corticosteroid dose must be stable for at least 1 month prior to 
study entry and expected to remain stable throughout participation. Any changes in systemic 
corticosteroid dose will be documented on the eCRF. Topical corticosteroids or 
immunosuppressive therapies to the face, groin, or scalp are allowed. 
Prior systemic treatment, including biologics, is to be recorded on the eCRF, including duration 
of exposure and reason for discontinuation. 
The concomitant medication names will be coded by the sponsor according to the World Health 
Organization (WHO) Drug Dictionary and classified by anatomical therapeutic chemical (ATC) 
categories. 
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11 SAFETY 
11.1 Safety Parameters 
The Clinical Symptom and Adverse Event Grading Scale will be used for grading toxicities (see 
Appendix E). With the exception of LFTs, laboratory results will be classified using the 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive 
Vaccine Clinical Studies (see Appendix A). LFTs will be classified using Table 9-2 in 
Section 9.4. Subjects will be monitored throughout the treatment and follow-up period for 
occurrence of AEs, as well as for changes in clinical status, vital sign measurements, and 
laboratory data. 
11.2 Adverse Event Definition 
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered drug related. AEs include: 
• Suspected adverse drug reactions (abbreviated as either SADR or SAR). This may be 
serious or not serious 
• Reactions from drug overdose, abuse, withdrawal, sensitivity, or toxicity 
• Significant changes or abnormalities, when compared with baseline, in structure 
(sign), function (symptom), clinical laboratory results, ECG results, or physiological 
testing. This includes any worsening of a pre-existing condition temporally 
associated with the use of study drug 
• Other medical events, regardless of their relationship to the study drug, such as injury, 
surgery, accidents, extensions of symptoms, or apparently unrelated illnesses 
For the purpose of data collection, all untoward events that occur after ICF through 30 days after 
last dose of study treatment are to be recorded on eCRFs by the investigational site. 
11.3 Evaluating Adverse Events 
The investigator will determine the seriousness, intensity, and causality of an AE associated with 
the use of the study drug (i.e., events where there is a reasonable possibility that the event may 
have been caused by the study drug) based on the definitions that follow. 
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11.3.1 Serious Adverse Events 
(Notify sponsor or designee within 24 hours; document on eCRF) 
The SAE definition and reporting requirements are in accordance with Title 21 Part Code of 
Federal Regulations (CFR) 312.32 and the Guidance for Industry and Investigators Safety 
Reporting Requirements for Investigational New Drug (ID) applications and 
bioavailability/bioequivalence (BA/BE) studies. 
SAE: An adverse event is considered "serious" if, in the view of either the investigator or 
sponsor, it results in any of the following outcomes: 
• Death: This includes any death that occurs while the subject is "on study" as well as any 
death that occurs within 30 days after study drug administration. 
Note: Death is an outcome of an AE, and not an AE in itself. The event(s) that 
caused death (e.g., illness, accident) is the SAE. Death due to any other 
cause(s) must also be reported as an outcome of the reportable SAE. 
• Life-threatening AE: An AE or suspected adverse reaction is considered 
"life-threatening" if, in the view of either the investigator or sponsor, its occurrence 
places the subject at immediate risk of death. It does not include an AE or suspected 
adverse reaction that, had it occurred in a more severe form, might have caused death. 
• Inpatient hospitalization or prolongation of existing hospitalization:  
In the absence of an AE, the investigator should not report hospitalization or prolongation 
of hospitalization. This is the case in the following situations: 
o Hospitalization or prolongation of hospitalization is needed for a procedure 
required by the protocol 
o Hospitalization or prolongation of hospitalization is part of routine procedure 
followed by study center 
o Hospitalization for survey visits or annual physicals 
In addition, a hospitalization planned before the start of the study for a pre-existing condition 
which has not worsened does not count as an SAE. 
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• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions  
• Congenital anomaly/birth defect 
• Important medical event: An event that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical 
judgment, it may jeopardize the subject and may require medical or surgical intervention 
to prevent 1 of the outcomes listed in this definition. 
11.3.2 Suspected Unexpected Serious Adverse Reaction 
(Notify sponsor or designee within 24 hours of first awareness; document on eCRF) 
A suspected unexpected serious adverse reaction (SUSAR) is any adverse drug event, the 
specificity or severity of which is not consistent with those noted in the current protocol and/or 
lB. This refers to any AE that has not been previously observed (e.g., included in the D3), rather 
than from the perspective of such an event not being anticipated from the pharmacological 
properties of the product. 
11.3.3 Unexpected Adverse Events 
An AE is considered "unexpected" if it is not listed in the lB or is not listed at the specificity or 
severity that has been observed; or, if an lB is not required or available, is not consistent with the 
risk infoimation described in the General Investigational Plan or elsewhere in the current 
application. The term also refers to AEs that are mentioned in the lB as occurring with a class of 
drugs or as anticipated from the pharmacological properties of the drug, but are not specifically 
mentioned as occurring with the particular drug under investigation. 
11.3.4 Non-Serious Adverse Events 
All other AEs, not fulfilling the previous definitions, are classified as non-serious. 
11.3.5 Protocol-Related Adverse Events 
AEs that are not study drug related may nevertheless be considered by the investigator or the 
medical monitor to be related to the conduct of the clinical study. That is, the event may be 
related to the fact that a subject is participating in the study. For example, a protocol-related AE 
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may be an event that occurs during a washout period or that is related to a procedure required by 
the protocol. 
11.3.6 Relationship to Study Drug 
The investigator will attempt to assess the relationship of the event to study drug using a 5-point 
scale (not related, unlikely related, possibly related, probably related, or definitely related; see 
Appendix F; Clinical Adverse Events: Determining Relationship to Study Drug). 
11.3.7 Recording Adverse Events 
All AEs (including SAEs) are to be accurately recorded on the Adverse Event page of the 
subject's eCRF during the subject's participation in the study. The severity of each AE will be 
graded using a 5-point scale (mild, moderate, severe, life threatening, or death; see Appendix E). 
The date of onset as well as the end date of the event also should be recorded or the event should 
be entered as "ongoing". In addition, the method used to treat the AE and the outcome of the AE 
also will be noted. The investigator will assess the relationship of the event to study drug. 
11.3.8 Hospitalization 
In the absence of an AE, the investigator should not report hospitalization or prolongation of 
hospitalization. This is the case in the following situations: 
• Hospitalization or prolongation of hospitalization is needed for a procedure required by 
the protocol. 
• Hospitalization or prolongation of hospitalization is part of routine procedure followed by 
study center. 
• Hospitalization for survey visits or annual physicals. 
In addition, a hospitalization planned before the start of the study for a pre-existing condition that 
has not worsened does not count as an SAE. 
11.3.9 Serious Adverse Event Reporting 
11.3.9.1 Governing Regulatory Requirements 
Compliance with this request for prompt reporting is essential in that the sponsor is responsible 
for informing the US FDA as well as all other participating investigators of the event. 
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Under FDA ruling (Title 21 CFR Part 312.32) and the Guidance for Industry and Investigators 
Safety Reporting Requirements for INDs and BA/BE Studies, the sponsor is required to submit 
written documentation, in the form of an IND safety report, detailing: 
• Any event associated with the use of the drug, that is both serious and unexpected, or 
• Any findings from clinical, epidemiological, or pooled analysis of multiple studies or any 
findings from animal or in vitro testing that suggest a significant risk in humans exposed 
to the drug. 
Written submission must be made by the sponsor to the FDA and the lRBs as soon as possible 
and in no event later than 15 calendar days after the sponsor's initial receipt of notification of the 
event. Any unexpected death or life-threatening suspected adverse reaction must be reported to 
FDA no later than 7 calendar days after the sponsor's initial receipt of the information. The 
sponsor shall also infoim all investigators. 
11.3.9.2 Time-Frame for Reporting 
Any death, pregnancy, SAE, or unexpected (and severe) AE experienced by a subject after ICF 
or within 30 days of receiving study drug, regardless of relationship to study drug, or any death 
that occurs more than 30 days after receiving study drug, and is believed to be study 
drug-related, must be promptly reported (within 24 hours of the investigator becoming aware of 
the event) by e-mail to the sponsor (or sponsor's designee). 
Contact infoimation for SAE/SUSAR reporting: 
INC Drug Safety 
Fax: (877) 464-7787 
Email: INCDrugSafety@lNCResearch.com  
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Additionally, the investigator will be able to contact the medical monitor at all times: 
John L Ryan, PhD, MD 
Kadmon Corporation 
450 East 29th Street 
New York, NY 10016 
Telephone: 	
Cell: (617) 230-4764 
E-mail: 	
john@kadmon.com  
11.3.9.3 Information to be Provided by the Investigator 
SAEs for all enrolled subjects must be recorded on both the SAE form and the AE eCRF page. 
This requirement includes all SAEs that occur after the subject signs the ICF and through 
30 days after last dose of study treatment, and in addition, any SAEs that are assessed as possibly 
related to study treatment by the investigator, even if the SAE occurs more than 30 days after the 
last dose of study treatment must be reported to the Kadmon Phannacovigilance Department. 
The minimum information required for SAE reporting includes identity of investigator, site 
number, subject number, an event description, SAE teim(s), onset date, the reason why the event 
is considered to be serious (i.e., the seriousness criteria) and the investigator's assessment of the 
relationship of the event to study treatment. Additional SAE information including medications 
or other therapeutic measures used to treat the event, action taken with the study treatment due to 
the event, and the outcome/resolution of the event will be recorded on the SAE form. Forms for 
reporting SAEs will be provided to the study sites. 
In all cases, the investigator should continue to monitor the clinical situation and report all 
material facts relating to the progression or outcome of the SAE. Furthermore, the investigator 
may be required to provide supplementary infoiniation as requested by the Kadmon Drug Safety 
personnel or designee. 
When reporting an SAE, the following additional points should be noted: 
• When the diagnosis of an SAE is known or suspected, the investigator should report 
the diagnosis or syndrome as the primary SAE term, rather than as signs or 
symptoms. Signs and symptoms may then be described in the event description. For 
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example, dyspnea should not be used as an SAE term if the diagnosis which caused 
the dyspnea is known to be malignant pleural effusion. 
• Death should not be reported as an SAE, but as an outcome of a specific SAE, unless 
the event preceding the death is unknown. In the exceptional case where the events 
leading to death are unknown, then death may be used as an event tetra. If an autopsy 
was performed, the autopsy report should be provided. 
• While most hospitalizations necessitate reporting of an SAE, some hospitalizations do 
not require SAE reporting, as follows: 
o Elective or previously scheduled surgery (e.g., a previously scheduled ventral 
hernia repair) 
o Procedures for pre-existing conditions that have not worsened after initiation 
of treatment 
o Pre-specified study hospitalizations for observation 
o Events that result in hospital stays of less than 24 hours and that do not require 
admission (e.g., an emergency room visit for hematuria that results in a 
diagnosis of cystitis and discharge to home on oral antibiotics) 
• SAEs must, however, be reported for any surgical or procedural complication 
resulting in prolongation of the hospitalization. 
11.3.9.4 Regulatory Reporting 
Kadmon Drug Safety (or designee) will process and evaluate all SAEs as soon as the reports are 
received. For each SAE received, Kadmon will make a determination as to whether the criteria 
for expedited reporting have been met. 
Kadmon (or designee) will submit SAEs that meet the criteria for expedited reporting to the 
Regulatory Authorities in accordance with local regulations governing safety reporting. 
Reporting of SAEs by the investigator to his or her IRB will be done in accordance with the 
standard operating procedures and policies of the IRB. Adequate documentation must be 
maintained showing that the IRB was properly notified. 
As a general rule, treatment codes will be broken by authorized member of the sponsor and/or 
designee Drug Safety staff before reporting an SAE that meets the criteria for expediting 
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reporting to the Regulatory Authorities. The investigator and sponsor staff that are not part of 
the Drug Safety Department will remain blinded to the treatment assignment. 
The blind should ordinarily be broken for IND safety reports submitted to the FDA. If a sponsor 
has concerns that unblinding of AEs will compromise the integrity of the study, the sponsor can 
propose in advance an alternative reporting format or frequency to maintain the blind that must 
be agreed to by the director of the review division in FDA with responsibility for review of the 
IND (21 CFR 312.32(c)(3)). Other Safety Considerations 
11.3.10 Laboratory Data 
All laboratory data obtained during the course of the study should be reviewed. Any abnoi 	
nal 
value that leads to a change in subject management (e.g., dose delay, requirement for additional 
medication or monitoring) or is considered to be of clinical significance by the investigator 
should be reported as an AE and/or SAE as appropriate, unless this value is consistent with the 
subject's present disease state or is consistent with values obtained prior to entry into the study. 
With the exception of LFTs, laboratory results will be classified using the Toxicity Grading 
Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical 
Studies (see Appendix A). LFTs will be classified using Table 9-2 in Section 9.4. 
11.3.11 Medication Errors 
Any medication error that results in an AE, even if it does not meet the definition of serious, 
requires reporting within 24 hours to the safety monitor. 
11.3.12 Follow-Up of Adverse Events 
Any SAE or AE assessed as possibly related that led to treatment discontinuation (including 
clinically significant abnormal laboratory values that meet these criteria) and is ongoing 30 days 
after last dose of study treatment must be followed until either resolution of the event or 
determination by the investigator that the event has become stable or irreversible. This 
follow-up guidance also applies to possibly related SAEs that occur more than 30 days after last 
dose of study treatment. The status of all other continuing AEs will be documented as, of 30 days 
after last dose of study treatment. 
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12 STATISTICAL CONSIDERATIONS 
All descriptive and inferential statistical analyses will be performed using SAS statistical 
software (Version 9.4), unless otherwise noted. For categorical variables, the number and 
percent of each category within a parameter will be calculated for non-missing data. For 
continuous variables, the mean, median, and standard deviation (SD), as well as the minimum 
and maximum values, will be presented. 
Statistical significance will be declared when the p-value is found to be < 0.05, unless otherwise 
noted. Missing data will not be imputed unless otherwise stated. All clinical data captured will 
be provided in data listings. 
Complete details of the planned analysis will be documented in the SAP. 
12.1 General Design 
All data for enrolled subjects will be presented in data listings by subject number. For those 
summary tables in which baseline and change from baseline measurements will be presented, the 
last observed measurement prior to the initial dose of KD025 will be considered the baseline 
measurement. 
Continuous data will be described using descriptive statistics: number of observations (n), mean, 
SD, median, minimum, and maximum. Frequencies and percentages will be used for 
summarizing discrete (categorical) data. When categorical data are presented, the percent will be 
suppressed when the count is zero in order to draw attention to the non-zero counts. The 
denominator for all percentages, unless otherwise specified, will be the number of subjects in the 
specified analysis population. Two-sided 95% confidence interval employing the exact binomial 
method will be provided for efficacy activity endpoints. 
Hypothesis testing, if appropriate, will be carried out at the 5% (2-sided) significance level. Due 
to the exploratory nature of the study, no adjustments may be made for the multiplicity of 
endpoints. Non-parametric tests may be used in preference to parametric tests if the underlying 
distributions of the data are not known. Missing values will not be imputed. If a subject does 
not have sufficient data for a particular analysis, then, that subject will be excluded from that 
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analysis. Endpoints defined as an average of multiple measurements will be used for those data 
points that were non-missing, and the denominator will be adjusted accordingly. 
12.2 Sample Size Justification 
The sample size will be 110 subjects due to early study termination. 
12.3 Study Populations 
Two populations will be employed in the analysis of study data: 
• The modified intent-to-treat (mITT) population will consist of all subjects who are 
randomized and take at least 1 dose of study drug. All safety analyses will be 
performed on the mITT population. The Evaluable for Efficacy population will 
consist of subjects who have non-missing baseline and Week 16 PAST scores and do 
not have a major protocol violation. 
Demographics, subject disposition, and screening and baseline characteristics will be 
summarized for mITT populations, where appropriate. 
12.4 Subject Accountability, Demographics, and Baseline Characteristics 
Subject disposition will be tabulated by treatment group. Similarly, subject demographic 
information and baseline characteristics will be displayed. 	
. 
12.5 KD025 Exposure 
The amount of KID 025 administered by visit and overall will be tabulated by treatment group and 
presented by subject in data listings. In addition, delays and all other alterations in KD025 
administration will be presented. 
12.6 Concomitant Medications 
Concomitant medications will be coded using WHO Drug Dictionary and the data will be 
summarized by treatment and presented in tables and listings. 
12.7 Efficacy Analysis 
The primary efficacy endpoint for analyses will be the number (%) of subjects with a 
75% decrease in PAST by Week 16. 
The secondary efficacy endpoints for analysis will include the following: 
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1. A 50% reduction in Week 16 PASI score (PAST 50) 
2. The mean Week 16 percent change from baseline in PAST 
3. Improvements in PGA of "clear" or "almost clear" at Week 16 
4. Improvements in DLQI at Week 16 
The exploratory efficacy endpoints are: 
• To evaluate the concentration and changes in IL-17 expression in blood, tissue, 
and other biomarkers in punch biopsy after 16 weeks of dosing with KD025 
Efficacy analyses will be divided into 2 periods: the double-blind treatment period through 
database lock at Week 16 and the open-label, 32-week continuation period. 
Efficacy analyses will include the number (%) of subjects with a 75% decrease in PAST (number 
of subjects that reach PAST 75) at Week 16 in the KD025 treatment groups compared with the 
placebo group in a pairwise manner using a Fisher's Exact test. The number of subjects who 
reach PAST 50 at Week 16 will be analyzed similarly. Treatment group differences in DLQI and 
PGA changes from baseline to Week 16 will be assessed using an analysis of covariance 
(ANCOVA) model with treatment as a fixed effect and a subject's baseline value as a covariate. 
No adjustments for multiplicity are being made for this Phase 2 study. 
For further details, see the statistical analysis plan (SAP). 
12.8 Safety Data 
Safety assessments will include AEs, SAEs, PEs (including weight), vital sign measurements 
(including BP, pulse rate, respiratory rate, and temperature), clinical laboratory evaluations 
(hematology, chemistry, urinalysis, coagulation, lipid panel, TSH) ECGs, and reasons for 
treatment discontinuation due to toxicity. 
The primary safety endpoint will be the percentage of subjects in each treatment group 
experiencing AEs. 
TEAEs will be summarized by treatment group using MedDRA® SOC and preferred term, 
classified from verbatim terms (Version 18.1 or higher). The incidence and percentage of 
subjects with at least 1 occurrence of a preferred term will be included, according to the most 
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severe grade using a 5-point scale (mild, moderate, severe, life threatening, or death). The 
number of events per preferred term will also be summarized. Causality (relationship to study 
treatment) will be summarized separately. 
AEs, SAEs, related AEs, related SAEs, > Grade 3 AEs, related > Grade 3 AEs, and AEs leading 
to withdrawal or treatment discontinuation will be summarized by treatment group according to 
SOC and preferred terms. AEs will also be presented in listings. Duration of AEs will be 
determined and included in listings, along with action taken and outcome. 
Laboratory results will be classified using the Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Studies (see Appendix A) and 
summarized. Incidence of laboratory abnormalities will be summarized by treatment group. The 
worst on-study grade after the first dose of study drug will be summarized by treatment group. 
The incidence of? Grade 3 laboratory abnormalities under treatment and shifts in toxicity 
grading from baseline to highest grade post-baseline will be displayed. 
Vital sign measurements will be summarized at each scheduled time point using descriptive 
statistics. 
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13 DATA QUALITY ASSURANCE 
Accurate and reliable data collection will be ensured by verification and cross-check of the 
eCRFs against the investigator's records by the study monitor (source document verification) and 
by the maintenance of a drug-dispensing log by the investigator. Collected data will be entered 
into a computer database and subject to electronic and manual quality assurance procedures. 
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14 ETHICAL ASPECTS 
14.1 Local Regulations 
The study must fully adhere to the principles outlined in "Guideline for Good Clinical Practice" 
ICH E6 Tripartite Guideline (January 1997), and in general, be conducted in a manner consistent 
with the most recent version of the Declaration of Helsinki. The investigator will ensure that the 
conduct of the study complies with the basic principles of GCP as outlined in the current version 
of 21 CFR, subpart D, Part 312, "Responsibilities of Sponsors and Investigators", Part 50, 
"Protection of Human Subjects", and Part 56,-  "Institutional Review Boards". 
14.2 Informed Consent Form 
Sample ICFs will be supplied to each site. Kadmon or its designee must review any ICF prior to 
submission for review by the IRB. The final IRB-approved document must be provided to 
Kadmon for regulatory purposes. 
It is the responsibility of the investigator, or a person designated by the investigator, to obtain a 
written ICF from each subject (or the subject's legally authorized representative) agreeing to 
participate in this study after adequate explanation of the aims, methods, anticipated benefits, and 
potential hazards of the study in accordance with federal and state regulations is provided. In the 
case where the subject is unable to read, an impartial witness should be present during the entire 
ICF discussion. After the subject has orally consented to participation in the study, the witness' 
signature on the form will attest that the information in the consent fowl was accurately 
explained and understood. A copy of the ICF must be provided to the subject or to the subject's 
legally authorized representative. If applicable, it will be provided in a certified translation of 
the local language. 
The eCRF for this study contains a section for documenting informed subject consent, and this 
must be completed appropriately. Signed ICFs must remain in each subject's study file and must 
be available for verification by study monitors at any time. If new safety information results in 
changes in the risk/benefit assessment, the consent form should be reviewed and updated as 
necessary. All subjects (including those already being treated) should be informed of the new 
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information, should be given a copy of the revised form, and should give their consent to 
continue in the study. 
14.3 Institutional Review Board 
This study is being conducted under a US IND application. This protocol (and any 
modifications) and appropriate consent procedures must be reviewed and approved by an IRB. 
This board must operate in accordance with the current federal or local regulations. The 
investigator will send a letter or certificate of IRB approval to Kadmon (or designee) before 
subject enrollment and whenever subsequent modifications to the protocol are made. 
14.4 Future Use of Subject Samples 
Not all of the tissue and blood components obtained during this study may be required for the 
tests that are part of the clinical study. Following the conclusion of the study, the samples may 
be used for additional research. This research will help to understand disease subtypes, drug 
response and toxicity, and possibly identify new drug targets or biomarkers that predict subject 
response to treatment. The use of the samples for internal research will be done according to the 
guidelines defined by the FDA guidance for In Vitro Diagnostic Device Studies Using Leftover 
Human Specimens that are Not Individual Identifiable (issued 25 April 25 2006) and the 
European Medicines Agency (EMEA) Reflection Paper on Pharmacogenetic Samples, Testing 
and Data Handling (EMEA/CHMP/PGxWP/201914/2006). If a subject requests destruction of 
their blood samples and the samples have not yet been de-identified, Kadmon will destroy the 
samples as described in this FDA guidance. Kadmon will notify the investigator in writing that 
the samples have been destroyed. 
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15 CONDITIONS FOR MODIFYING THE PROTOCOL 
Protocol modifications to ongoing studies must be made only after consultation between a 
Kadmon representative and the investigator. Protocol modifications will be reviewed and 
approved by Kadmon representatives. 
All protocol modifications must be submitted to the lin for information and approval in 
accordance with local requirements, and to regulatory agencies if required. Approval must be 
obtained before any changes can be implemented, except for changes necessary to eliminate an 
immediate hazard to study subjects, or when the change involves only logistical or administrative 
aspects of the study (e.g., change in monitor, change of telephone number). 
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16 CONDITIONS FOR TERMINATING THE STUDY 
Kadmon has the right to terminate the study at any time. In terminating the study, Kadmon and 
the investigator will ensure that adequate consideration is given to the protection of the subjects' 
interests. 
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17 STUDY DOCUMENTATION, CRFS, AND RECORD KEEPING 
17.1 Investigator's Files and Retention of Documents 
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 2 separate categories as follows: (1) investigator's study files; and (2) subject 
clinical source documents. 
The investigator's study file will contain the protocol and protocol amendments, eCRFs, lRB, 
and governmental approval with correspondence, sample ICF, drug records, staff curriculum 
vitae and authorization forms, and other appropriate documents and correspondence. 
Subject clinical source documents (usually predefined by the project to record key efficacy and 
safety parameters independent of the eCRFs) may include subject hospital/clinic records, 
physician's and nurse's notes, appointment book, original laboratory reports, ECG, 
electroencephalogram, X-ray, pathology, and special assessment reports, signed ICFs, consultant 
letters, and subject screening and enrollment logs. The investigator must keep these 2 categories 
of documents on file for at least 2 years following the marketing application approval date for the 
study treatment and for the indication being investigated or for 2 years after the investigation is 
discontinued and the FDA notified. After that period of time, the documents may be destroyed 
subject to local regulations with prior written permission from Kadmon. If the investigator 
wants to assign the study records to another party or move them to another location, Kadmon 
must be notified in advance. 
If the investigator cannot guarantee the archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and Kadmon to 
store these in a sealed container outside of the study site so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storing outside of the study site. 
17.2 Source Documents and Background Data 
Upon request, the investigator will supply Kadmon with any required background data from the 
study documentation or clinic records. In case of special problems or governmental queries or 
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requests for audit inspections, it is also necessary to have access to the complete study records, 
provided that subject confidentiality is protected. 
17.3 Audits and Inspections 
The investigator should understand that source documents for this study should be made 
available to appropriately qualified personnel from the Kadmon Quality Assurance Unit (or 
designee), or to health authority inspectors after appropriate notification. The verification of the 
eCRF data must be by direct inspection of source documents. 
17.4 Electronic Case Report Forms 
Clinical study data for this study will be captured on eCRF. The investigator agrees to provide 
all information requested on the eCRF in an accurate manner according to instructions provided. 
eCRFs are designed for computer processing and analysis. The investigator should ensure the 
accuracy, completeness, and timeliness of the data reported to Kadmon in the eCRF and in all 
required reports. 
An eCRF is required to be submitted for every subject who receives any amount of study drug. 
This includes submission of retrievable data on subjects who withdraw before completion of the 
study. If a subject stops treatment or terminates from the study, the dates and reasons must be 
noted on the eCRF. 
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18 MONITORING THE STUDY 
It is understood that the responsible Kadmon monitor (or designee) will contact and visit the 
investigator regularly and will be allowed on request to inspect the various records of the study 
(eCRFs and other pertinent data), provided that subject confidentiality is maintained in 
accordance with local requirements. 
It will be the monitor's responsibility to inspect the eCRFs at regular intervals throughout the 
study, to verify the adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them. The monitor should have access to laboratory test reports and 
other subject records needed to verify the entries on the eCRF. The investigator (or designee) 
must agree to cooperate with the monitor to ensure that any problems detected in the course of 
these monitoring visits are resolved. 
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19 CONFIDENTIALITY OF STUDY DOCUMENTS AND SUBJECT RECORDS 
The investigator must ensure that subjects' anonymity will be maintained and that their identities 
are protected from unauthorized parties. On eCRFs or other documents submitted to Kadmon, 
subjects should be identified by an identification code and not by their names. The investigator 
should keep a subject enrollment log showing codes, names, and addresses. The investigator 
should maintain documents not for submission to Kadmon (e.g., subjects' written consent forms) 
in strict confidence. 
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20 PUBLICATION OF DATA AND PROTECTION OF TRADE SECRETS 
The results orthis study may be published or presented at scientific meetings. The investigator 
agrees to submit all manuscripts or abstracts to Kadmon for review at least 30 days before 
submission. This allows Kadmon to protect proprietary information and to provide comments 
based on information from other studies that may not yet be available to the investigator. 
In the event that Kadmon coordinates a publication or presentation of study results from all study 
sites, the participation of investigator or other representatives of study site as a named author 
shall be determined in accordance with Kadmon policy and generally accepted standards for 
authorship. 
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21 REFERENCES 
CDER-PHRMA-AASLD Conference. Clinical White Paper. Drug-Induced Liver Injury: A National 
and Global Problem. 2000 
http://www.fda.gov/downloads/Drugs/ScienceResearch/ResearchAreas/ucm091457.pdf.  
Cobert, B. (2012). Cobert's Manual of Drug Safety and Phannacovigilance (2nd ed.). 
Massachusetts: Jones & Bartlett Learning, LLC. 
Dufour, DR, Lott JA, Nolte FS, et al. Diagnosis and Monitoring of Hepatic Injury I, Performance 
Characteristics of Laboratory Tests. Clin Chem. 2000a; 46(12):2027-49. 
Dufour, DR, Lott JA, Nolte FS, et al. Diagnosis and Monitoring of Hepatic Injury 
Recommendations for Use of Laboratory Tests in Screening, Diagnosis, and Monitoring. Clin Chem. 
2000b;46(12):2050-68. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): A simple practical measure for 
routine clinical use. Clinical and Experimental Dermatology 1994; 19:210-216. 
Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University 
School of Medicine (2007). "iclinphainilddis/clinical-table/" Accessed Dec 16, 2016. 
Food and Drug Administration (FDA). Guidance for Industry. Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. US Department of 
Health and Human Services, Center for Biologics Evaluation and Research. September 2007. 
Kadmon KD025 Investigator's Brochure. Sept 2015, version 5.0. 
Nohria A, Grunert M, Rikitake Y, et al. Rho kinase inhibition improves endothelial function in 
human subjects with coronary artery disease. Circ Res. 2006; 99:1426-1432. 
Robinson A, Kardos M, Kimball AB. Physician Global Assessment (PGA) and Psoriasis Area 
and Severity Index (PAST): why do both? A systematic analysis of randomized controlled trials 
of biologic agents for moderate to severe plaque psoriasis. J Am Acad Dennatol. 2012 
Mar;66(3):367-75. 
Vicari RM, Chaitman B, Keefe D, et al. Efficacy and safety of fasudil in patients with stable 
angina: a double-blind, placebo-controlled, phase 2 trial. J Am Coll Cardiol. 2005 Nov 
15;46(10):1803-11. 
Wozel J. The Psoriasis Area and Severity Index Is the Adequate Criterion to Define Severity in 
Chronic Plaque-Type Psoriasis. Demi. 005;210:194-199. 
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Appendix A: Tables for Grading Laboratory Abnormalities 
The laboratory values provided in the tables below serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
Note: For LFT and bilirubin abnormalities, see Table 9-2 in Section 9.4. 
Chemistry* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life 
Threatening 
(Grade 4)** 
Sodium - Hyponatremia mEq/L 
132 - 134 
130 - 131 
125 - 129 
<125 
Sodium - Hypernatremia 
mEq/L 
144 - 145 
146 - 147 
148 - 150 
>150 
Potassium - Hyperkalemia 
mEq/L 
5.1 - 5.2 
5.3 - 5.4 
5.5 - 5.6 
>5.6 
Potassium - Hypokalemia 
mEq/L 
3.5 - 3.6 
3.3 - 3.4 
3.1 - 3.2 
<3.1 
Glucose-Hypoglycemia 
mg/dL 
65 - 69 
55 - 64 
45 - 54 
<45 
Glucose - 
Hyperglycemia 
Fasting - mg/dL 
Random - mg/dL 
100 - 110 
110- 125 
111 - 125 
126 -200 
>125 
>200 
Insulin 
requirements 
or 
hyperosmolar 
coma 
Blood Urea 
Nitrogen 
BUN mg/dL 
23 -26 
27 - 31 
> 31 
Requires 
dialysis 
Creatinine - mg/dL 
1.5 - 1.7 
1.8 -2.0 
2.1 -2.5 
>2.5 or 
requires 
dialysis 
Calcium - hypocalcemia mg/dL 
8.0 - 8.4 
7.5 -7.9 
7.0 -7.4 
<7.0 
Calcium- hypercalcemia 
mg/dL 
10.5 - 11.0 
11.1- 11.5 
11.6- 12.0 
> 12.0 
Magnesium - hypomagnesemia 
mg/dL 
1.3 - 1.5 
1.1 - 1.2 
0.9- 1.0 
<0.9 
Phosphorous - 
hypophosphatemia 
mg/dL 
2.3 -2.5 
2.0 - 2.2 
1.6 - 1.9 
<1.6 
CPK - mg/dL 
1.25 - 1.5 x 
ULN*** 
1.6 - 3.0 x ULN 
3.1 -10 x ULN 
> 10 x ULN 
Albumin - Hypoalbuminemia 
g/dL 
2.8-3.1 
2.5 - 2.7 
<2.5 
-- 
Total Protein - 
Hypoproteinemia g/dL 
5.5 - 6.0 
5.0 - 5.4 
<5.0 
-- 
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Chemistry* 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
Life 
Threatening 
(Grade 4)** 
Cholesterol 
201 -210 
211 -225 
>226 
--- 
Pancreatic enzymes - amylase, 
lipase 
1.1 - 1.5 x ULN 
1.6 - 2.0 x ULN 
2.1 - 5.0 x ULN 
>5.0 x ULN 
*The laboratory values provided in the tables serve as guidelines and are dependent upon institutional normal 
parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
** The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of 
the laboratory abnormalities as Potentially Life Threatening (Grade 4). For example, a low sodium value 
that falls within a grade 3 parameter (125-129 mFq/L) should be recorded as a grade 4 hyponatremia 
event if the subject had a new seizure associated with the low sodium value. 
***ULN" is the upper limit of the normal range. 
Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Hemoglobin (Female) - 
gm/dL 
11.0 - 12.0 
9.5 - 10.9 
8.0 - 9.4 
<8.0 
Hemoglobin (Female) 
change from baseline value 
- gm/dL 
Any decrease -1.5 
1.6 -2.0 
2.1 - 5.0 
>5.0 
Hemoglobin (:Male) - 
_gm/dL 
12.5- 13.5 
10.5 - 12.4 
8.5- 10.4 
<8.5 
Hemoglobin (Male) 
change from baseline value 
- gm/dL 
Any decrease - 1.5 
1.6 - 2.0 
2.1 -5.0 
> 5.0 
WBC Increase - cell/mm3  
10,800 - 15,000 
15,001 -20,000 
20,001 -25, 000 
>25,000 
WBC Decrease - cell/mm3  
2,500 -3,500 
1,500 -2,499 
1,000 - 1,499 
<1,000 
Lymphocytes Decrease - 
cell/mm3  
750 - 1,000 
500 - 749 
250 - 499 
<250 
Neutrophils Decrease - 
cell/mm3  
1,500 -2,000 
1,000 - 1,499 
500 - 999 
<500 
Eosinophils - cell/mm3  
650 - 1500 
1501 - 5000 
> 5000 
Hypereosinophilic 
Platelets Decreased - 
cell/mm3  
125,000 - 140,000 
100,000 - 124,000 
25,000 -99,000 
<25,000 
PT - increase by factor 
(prothrombin time) 
1.0 - 1.10 x 
ULN** 
1.11- 1.20 x ULN 
1.21 -1.25 x ULN 
> 1.25 ULN 
PTT - increase by factor 
(partial thromboplastin 
time) 
1.0 - 1.2 x ULN 
1.21- 1.4 x ULN 
1.41 -1.5 )< ULN 
> 1.5 x ULN 
Fibrinogen increase - 
mg/dL 
400 - 500 
501 - 600 
>600 
-- 
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Hematology * 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Fibrinogen decrease - 
mg/dL 
150 — 200 
125 — 149 
100— 124 
<100 or associated 
with gross bleeding 
or disseminated 
intravascular 
coagulation (DIC) 
The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
** 	
"ULN" is the upper limit of the normal range. 
Urine * 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Protein 
Trace 
1+ 
• 
2+ 
Hospitalization or 
dialysis 
Glucose 
Trace 
1+ 
2+ 
Hospitalization for 
 
hyperglycemia 
Blood 
(microscop 
ic) — red 
blood cells 
1 - 10 
11 — 50 
> 50 and/or 
gross blood 
Hospitalization or 
packed red blood 
cells (PRBC) 
transfusion 
* 	
The laboratory values provided in the tables serve as guidelines and are dependent upon 
institutional normal parameters. Institutional normal reference ranges should be provided to 
demonstrate that they are appropriate. 
Food and Drug Administration (FDA). Guidance for Industry. Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials. US Department 
of Health and Human Services, Center for Biologics Evaluation and Research. September 2007. 
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Appendix B: Correction for Heart Rate (Fridericia)* 
The following formula will be used to correct to QT interval: 
QT  
QTF 
RR,I3 
Wheie QTF is the QT interval corrected for heart rate, and RR is the cube root of the interval 
from the onset of 1 QRS complex to the onset of the next QRS complex. 
*Fridericia LS (1920). "The duration of systole in the electrocardiogram of normal subjects and of patients with 
heart disease." Acta Medica Scandinavica. (53): 469-486. 
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Appendix C: Relative Physician's Global Assessment 
The relative PGA documents the physician's assessment of the subject's psoriasis status. 
Consideration should be given to the percent of body involvement as well as overall induration, 
scaling, and erythema. The PGA is assessed relative to baseline condition and is defined as: 
(1) = clear, (2) = excellent, (3) = good, (4) = fair, (5) = poor, and (6) = worse. The following 
table further defines the rating. 
Rating 
% Clearing 
Definition of Response 
1 = Clear 
100% clear 
Some residual pinkness or pigmentation: 
Woronoff s ring may be present. 
2= Excellent 
75 to 99% clearing Marked improvement: nearly normal skin 
texture; some erythema may be present. 
3 = Good 
50 to 74% clearing 
Moderate improvement: plaque has cleared to 
point of small scattered papules with normal 
intervening epidermis. 
= 
4 	
Fair 
25 to 49% clearing  Slight improvement: decrease in scaling and 
softening of plaque. 
5 = Poor 
0 to 24% clearing 
Little or no change in scaling, erythema, or 
plaque elevation. 
6 = Worse 
Worse 
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Appendix D: Dermatology Life Quality Index 
The aim of this questionnaire is to measure how much your skin problem has 
affected your life OVER THE LAST WEEK. Please tick El one box for each question. 
1. 
Over the last week, how itchy, sore, 
painful or stinging has your skin 
been? 
2. 
Over the last week, how embarrassed 
or self-conscious have you been because 
of your skin? 
3. 
Over the last week, how much has your 
skin interfered with you going 
shopping or looking after your home or 
garden? 
relevant El 
4. 
Over the last week, how much has your 
skin influenced the clothes 
you wear? 
relevant CI 
5. 
Over the last week, how much has your 
skin affected any social or 
leisure activities? 
relevant CI 
6. 
Over the last week, how much has your 
skin made it difficult for 
you to do any sport? 
relevant CI 
7. 
Over the last week, has your skin prevented 
you from working or studying? 
relevant 0 
If "No", over the last week how much has 
your skin been a problem at 
work or studying? 
Very much 
A lot 
A little 
Not at all 
Very much 
A lot 
A little 
Not at all 
Very much 
A lot 
A little 
Not at all 
Very much 
A lot 
A little 
Not at all 
Very much 
A lot 
A little 
Not at all 
Very much 
A lot 
A little 
Not at all 
Yes 
No 
A lot 
A little 
Not at all 
El 
El 
Cl 
CI 
El 
0 	
Not 
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KDO25 	
lND Number 120787 
Protocol Number KDO25-211 
8. 
Over the last week, how much has your 
skin created problems with your 
partner or any of your close friends 
or relatives? 
relevant 0 
9. 
Over the last week, how much has your 
skin caused any sexual 
difficulties?  
Very much 
A lot 
A little 
Not at all 
Very much 
A lot 
A little 
Not at all 
0 
O 
0 
O 
Not 
0 
CI 
0 
0 	
Not 
relevant CI 
10. 	
Over the last week, how much of a 	
Very much 
0 
problem has the treatment for your 	
A lot 	0 
skin been, for example by making 	
A little 	
0 
your home messy, or by taking up time? 	
Not at all 	
O 	
Not 
relevant CI 
Please check you have answered EVERY question. Thank you. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): A simple practical measure for routine clinical use. 
Clinical and Experimental Dermatology 1994; 19: 210-216. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Appendix E: Clinical Symptom and Adverse Event Grading Scale 
CLINICAL ADVERSE EVENT GRADING 
Severity 
Grade 
Definition 
Mild 
1 
Awareness of symptom, but easily tolerated. Usually transient 
requiring no special treatment; does not interfere with usual 
status or activities 
Moderate 
2 
May be ameliorated by simple therapeutic measures; may 
interfere with usual activities 
Severe 
3 
Incapacitating; unable to perform usual activities 
Life-threatening 
4 
Requires immediate intervention; need for emergency treatment 
Death 
5 
Resulting in the subsequent death of the subject 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Appendix F: Clinical Adverse Events: Determining Relationship to Study Drug 
1 	
NOT RELATED 
This category applies to those AEs which, after careful medical consideration, are clearly felt to 
be due to extraneous causes (disease, environment, etc.) that are unrelated to the administration of 
study drug. 
2 	
UNLIKELY RELATED (must have first 2) 
This category applies to those AEs which, after careful medical consideration, are felt unlikely to 
be related to the administration of the study drug. The relationship of an AE to the study drug can 
be considered unlikely if: 
• It does not follow a reasonable temporal sequence from administration of the drug. 
• It could readily have been a result of the subject's clinical state, environmental or toxic factors, 
or other modes of therapy administered to the subject. 
• It does not follow a known response pattern to the suspected drug. 
• It does not reappear or worsen when the drug is re-administered. 
3 	
POSSIBLY RELATED (must have first 2) 
This category applies to those AEs which, after careful medical consideration, are felt unlikely to 
be related to the administration of the study drug, but the possibility cannot be ruled out with 
certainty. The relationship of an AE to the study drug can be considered possible if: 
• It follows a reasonable temporal sequence from administration of the drug. 
• It could readily have been a result of the subject's clinical state, environmental or toxic factors, 
or other modes of therapy administered to the subject. 
• It follows a known response pattern to the suspected drug. 
4 	
PROBABLY RELATED (must have first 3) 
This category applies to those AEs which, after careful medical consideration, are felt with a high 
degree of certainty to be related to the administration of the study drug. The relationship of an AE 
to the study drug can be considered probable if: 
• It follows a reasonable temporal sequence from administration of the drug. 
• It could not be reasonably explained by the known characteristics of the subject's clinical state, 
environmental or toxic factors or other modes of therapy administered to the subject. 
• It disappears or decreases upon cessation of drug or reduction in dose.* 
• It follows a known response pattern to the suspected drug. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
5 	
DEFINITELY RELATED (must have first 3) 
This category applies to those AEs, which, after careful medical consideration, are felt to be 
related to the administration of the study drug. The relationship of an AE to the study drug can be 
considered related if: 
• It follows a reasonable temporal sequence from administration of the drug or drug levels have 
been established in body fluids or tissues. 
• It could not be reasonably explained by the known characteristics of the subject's clinical state, 
environmental or toxic factors or other modes of therapy administered to the subject. 
• It disappears or decreases upon cessation of drug or reduction on dose and appears upon 
rechallenge.* 
• It follows a known response pattern to the suspected drug. 
*There are exceptions when an AE does not disappear upon discontinuation of the drug, yet drug 
relatedness clearly exists. 
Cobert, B. (2012). Cobert's Manual of Drug Safety and Pharmacovigilance (2nd ed.). Massachusetts: Jones & 
Bartlett Learning, LLC. 
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KDO25 	
IND Number 120787 
Protocol Number KDO25-211 
Appendix G: CYP3A4Inducersand inhibitors 
Use of these drugs should be avoided in subjects who are receiving KD025 unless deemed 
clinically necessary (Flockhart 2007): 
Inhibitor/Inducer 
Drug Name 
Inhibitors 
indinavira 
nelfinavir a  
ritonavir a  
clarithromycin a 
itraconazole a 
ketoconazole a 
nefazodone a  
erythromycinb 
grapefruit juice b  
verapamil b  
suboxone b  
diltiazemb 
cimetidinee 
amiodarone 
fluvoxamine 
troleandomycin 
voriconazole 
Inducers 
carbamazepine 
efavirenz 
nevirapine 
phenobarbital 
phenytoin 
pioglitazone 
rifabutin 
rifampin 
St. John's Wort 
troglitazone 
a. 
A Strong inhibitor is one that causes a> 5-fold increase in the plasma AUC values or more than 80% decrease in clearance. 
b. 
A Moderate inhibitor is one that causes a> 2-fold increase in the plasma AUC values or 50-80% decrease in clearance. 
A Weak inhibitor is one that causes a> 1.25-fold but <2-fold increase in the plasma AUC values or 20-50% decrease in clearance. 
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