Clinical trial NCT03802344
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics
Start date: 2018-12-12; Completion date: 2019-10-02
Enrollment: 498 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This trial is a randomized, investigator-blind, multicentre, vehicle- and comparator-controlled, parallel-group trial with the purpose of evaluating the efficacy, safety and convenience of the MC2-01 cream.

Detailed description:
The MC2-01 Cream is designed for optimal patient satisfaction - it quickly absorbs into the skin leaving it nicely moisturized allowing patients to move on in daily routines. In this trial, the MC2-01 cream will be compared to a marketed product CAL/BDP combination and vehicle. The purpose of the trial is to compare the clinical efficacy, safety, and convenience of this cream to the marketed product. The trial will include a 8-week treatment period.

Arms: arm 1: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0,005%/0,064%) cream. One application daily for 8 weeks arm 2: Calcipotriene/betamethasone (Calcipotriene/betamethasone dipropionate, w/w 0,005%/0,064%) cream. One application daily for 8 weeks arm 3: One application daily for 8 weeks
Interventions: intervention 1: MC2-01 cream intervention 2: Cal/BDP combination intervention 3: Vehicle
Intervention descriptions: intervention 1: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0,005%/0,064%) cream intervention 2: Calcipotriene/betamethasone dipropionate, w/w 0,005%/0,064% intervention 3: Vehicle cream

Protocol documents:
Prot_000.pdf: 
MC2 Therapeutics 
Clinical Trial Protocol 
MC2-01-C7 
16 October 2018 
Version 2.0 
 
 
 
Clinical Trial Protocol 
 
Trial Title: 
A Randomised, Multicentre, Investigator-Blind, Parallel-
Group Trial to Evaluate the Efficacy and Safety of MC2-01 
Cream Compared to Vehicle and Active Comparator in 
Subjects with Mild-to-Moderate Psoriasis Vulgaris 
 
 
Investigational product: 
MC2-01 (calcipotriol/betamethasone dipropionate, 
0.05/0.64 mg/g) cream 
 
Active Comparator: 
Calcipotriol/betamethasone (calcipotriol/betamethasone 
dipropionate, 0.05/0.64 mg/g) gel 
 
Protocol No: 
MC2-01-C7 
 
IND number: 
127152 
 
EudraCT number: 
2018-001970-66 
 
Development phase: 
3 
 
Documents status: 
Final 
 
Document version: 
Version 2.0 
 
Document date: 
16 October 2018  
 
 
  
 
 
 
Sponsor: 
 
 
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
 
 
 
 
c/o Agern Alle 24-26 
 
 
 
 
2970 Hoersholm 
 
 
 
 
Denmark 
 
 
 
 
(“MC2”) 
 
 
Property of MC2 Therapeutics 
Confidential 
The confidential information provided in this document is for use by parties directly involved in this 
investigation. This document is delivered in confidence that such information will not be copied or 
made available to any third party without the written consent of MC2 Therapeutics.   


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CLINICAL TRIAL PROTOCOL APPROVAL 
Product: MC2-01 (calcipotriol/betamethasone dipropionate) cream 
Protocol number: MC2-01-C7 
Protocol title: A Randomised, Multicentre, Investigator-Blind, Parallel-Group Trial to 
Evaluate the Efficacy and Safety of MC2-01 Cream Compared to Vehicle and Active 
Comparator in Subjects with Mild-to-Moderate Psoriasis Vulgaris 
The following persons have approved this clinical trial protocol, which are separate 
documents adjoined to this document: 
Johan Selmer, MD, VP Medical Affairs, MC2 Therapeutics                                 
Charlotte Hindsberger, Principal consultant, Biostatistics, S-cubed 
 
Matthias Augustin, Prof. Dr. med, International Coordinating Investigator, University 
Medical Center Hamburg-Eppendorf 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
Product: MC2-01 (calcipotriol/betamethasone dipropionate; 0.05/0.64 mg/g) cream 
Protocol number: MC2-01-C7 
Version: 2 
Protocol title: A Randomised, Multicentre, Investigator-Blind, Parallel-Group Trial to 
Evaluate the Efficacy and Safety of MC2-01 Cream Compared to Vehicle and Active 
Comparator in Subjects with Mild-to-Moderate Psoriasis Vulgaris. 
The signature of the trial investigator below constitutes his/her approval of this protocol and 
provides the necessary assurances that this trial will be conducted according to all stipulations, 
clinical and administrative, as detailed in the protocol. The trial will not be initiated without 
the approval of an appropriate Institutional Review Board or Ethics Review Committee. 
 
 
 
Principal investigator’s printed name 
 
 
 
 
Principal investigator’s signature 
 
Date 
 
 
 
 


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TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF TABLES .........................................................................................................................7 
LIST OF FIGURES .......................................................................................................................7 
1.0 
SYNOPSIS ..........................................................................................................................10 
2.0 
INTRODUCTION ..............................................................................................................17 
2.1 
Background ..............................................................................................................17 
2.2 
Rationale of the Trial ................................................................................................18 
2.3 
Benefit-risk Assessment ...........................................................................................18 
3.0 
TRIAL OBJECTIVES AND PURPOSE ..........................................................................19 
4.0 
TRIAL DESIGN .................................................................................................................19 
4.1 
Overall Trial Design .................................................................................................19 
4.2 
Trial Endpoints .........................................................................................................20 
5.0 
SELECTION OF TRIAL POPULATION .......................................................................21 
5.1 
Subject Population ....................................................................................................21 
5.2 
Inclusion Criteria ......................................................................................................22 
5.3 
Exclusion Criteria .....................................................................................................23 
5.4 
Withdrawals and Discontinuation of Treatment ......................................................24 
5.5 
Replacement Policy ..................................................................................................25 
6.0 
TRIAL TREATMENTS ....................................................................................................26 
6.1 
Investigational Product .............................................................................................26 
6.1.1 
MC2-01 cream ..............................................................................................26 
6.1.2 
MC2-01 cream vehicle .................................................................................26 
6.1.3 
Active Comparator Product ..........................................................................26 
6.2 
Dosing Regimen .......................................................................................................26 
6.3 
Dose Modification ....................................................................................................27 
6.4 
Packaging, Labeling, Storage and Destruction ........................................................27 
6.5 
Assignment to Treatment .........................................................................................28 
6.5.1 
Randomisation ..............................................................................................28 
6.5.2 
Blinding ........................................................................................................28 
6.6 
Prior, Concomitant, and Prohibited Therapy ...........................................................28 
6.6.1 
Washout of prohibited medications prior to enrolment ...............................28 
6.6.2 
Prohibited medications during the trial ........................................................29 
6.6.3 
Allowed treatment outside the treatment area ..............................................29 


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6.7 
Treatment Compliance .............................................................................................29 
7.0 
VISIT SCHEDULE AND ASSESSMENTS .....................................................................30 
7.1 
Demographics and Medical History .........................................................................32 
7.2 
Prior and Concomitant Medication ..........................................................................32 
7.3 
Concurrent diagnoses ...............................................................................................32 
7.4 
Physical Examination ...............................................................................................33 
7.5 
Vital Signs ................................................................................................................33 
7.6 
Pregnancy Test .........................................................................................................33 
7.7 
Laboratory Assessments ...........................................................................................33 
7.7.1 
Biochemistry and Urinalysis ........................................................................33 
7.8 
Investigator Assessments .........................................................................................34 
7.8.1 
Body surface area (BSA) involvement of psoriasis vulgaris on the body....34 
7.8.2 
Modified Psoriasis Area and Severity Index (mPASI) ................................34 
7.8.3 
Physician’s global assessment of psoriasis severity .....................................36 
7.8.4 
Local skin reactions ......................................................................................36 
7.9 
Patient Reported Outcomes (PROs) .........................................................................38 
7.9.1 
Subject Global Assessment of disease severity (SGA) ................................38 
7.9.2 
Dermatology Life Quality Index (DLQI) .....................................................38 
7.9.3 
EuroQOL five dimensions questionnaire (EQ-5D) ......................................38 
7.9.4 
The Psoriasis Treatment Convenience Scale ...............................................38 
7.9.5 
Photography .................................................................................................39 
7.10 
Adverse Events .........................................................................................................39 
7.10.1 
Adverse events assessments .........................................................................39 
7.10.2 
Timing ..........................................................................................................40 
7.10.3 
Severity of adverse events ............................................................................40 
7.10.4 
Relationship of an adverse event to trial treatment ......................................40 
7.10.5 
Unexpected adverse events ..........................................................................41 
7.10.6 
Trial medication overdose ............................................................................41 
7.10.7 
Pregnancy .....................................................................................................41 
7.10.8 
Serious adverse event ...................................................................................41 
7.10.9 
Reporting of Serious Adverse Events and Pregnancies ...............................43 
7.10.9.1 
Contact person(s) and number(s)....................................................43 
7.10.9.2 
Reporting procedures ......................................................................43 
7.11 
Unscheduled Visit ....................................................................................................43 
7.12 
Follow-up Visit ........................................................................................................43 


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7.13 
Early Termination ....................................................................................................44 
8.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
STATISTICAL AND ANALYTICAL PLANS ...............................................................45 
8.1 
General Considerations for Data Analysis ...............................................................45 
8.2 
Sample Size and Power Considerations ...................................................................45 
8.3 
Analysis Populations ................................................................................................47 
8.4 
Estimands .................................................................................................................48 
8.5 
Handling of Missing Data ........................................................................................48 
8.6 
Analyses of Efficacy ................................................................................................49 
8.6.1 
Primary Efficacy Endpoint ...........................................................................50 
8.6.1.1 
Analysis of primary endpoint ..........................................................50 
8.6.1.2 
Sensitivity analyses..........................................................................51 
8.6.2 
Secondary Efficacy Endpoints .....................................................................51 
8.6.2.1 
Sensitivity analyses..........................................................................52 
8.6.3 
Other Endpoints ............................................................................................52 
8.6.3.1 
Analysis of other endpoints .............................................................53 
8.7 
Analysis of Safety ....................................................................................................54 
8.7.1 
Adverse events .............................................................................................54 
8.7.2 
Local Skin Reaction Assessment .................................................................54 
8.7.3 
Other safety variables ...................................................................................54 
9.0 
CHANGES IN THE PLANNED TRIAL .........................................................................55 
9.1 
Protocol Amendments ..............................................................................................55 
9.2 
Termination or Suspension of the Trial ....................................................................55 
10.0 DATA HANDLING AND RECORD KEEPING ............................................................55 
10.1 
Recording of Data ....................................................................................................55 
10.1.1 
Source documents ........................................................................................55 
10.1.2 
Case report forms .........................................................................................56 
10.2 
Retention of Documents ...........................................................................................56 
11.0 QUALITY CONTROL AND QUALITY ASSURANCE ...............................................56 
11.1 
Direct Access to Source Documents ........................................................................56 
11.2 
Monitoring Procedures .............................................................................................57 
11.3 
Audit and Inspection ................................................................................................57 
12.0 ETHICS ...............................................................................................................................57 
12.1 
Ethical Conduct of the Trial .....................................................................................57 
12.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) ...........57 


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12.3 
Subject Information and Consent .............................................................................57 
12.4 
Disclosure and Confidentiality .................................................................................58 
12.4.1 
Confidentiality of trial documentation .........................................................58 
12.4.2 
Privacy of individual health information .....................................................58 
13.0 EMERGENCY PROCEDURES .......................................................................................58 
13.1 
Emergency Unblinding ............................................................................................58 
14.0 INSURANCE ......................................................................................................................58 
15.0 PUBLICATION POLICY .................................................................................................59 
16.0 REFERENCES ...................................................................................................................60 
17.0 APPENDICES ....................................................................................................................64 
17.1 
Appendix 1  Contact List of MC2 and Protocol Authors .........................................64 
17.2 
Appendix 2 Vendors .................................................................................................65 
17.3 
Appendix 3 Classification of Topical Corticosteroids - Examples ..........................66 
 
LIST OF TABLES 
 
Table 7-1 Visit Schedule ................................................................................................................30 
Table 7-2 Fitzpatrick Skin Type Classification .............................................................................32 
Table 7-3 Physician’s Global Assessment (PGA) .........................................................................36 
Table 7-4 Local Skin Reaction Scores ...........................................................................................37 
Table 8-1 Published mean reduction of PASI for active treatment from baseline to 8-weeks 
reported in CAL/BDP Gel phase 2/3 trials .................................................................46 
Table 8-2 Published mean reduction of PASI for active treatment from baseline to 8-weeks 
reported in CAL/BDP Ointment phase 3 trials ...........................................................46 
 
LIST OF FIGURES 
Figure 4-1  Trial Design ................................................................................................................20 
 


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List of Abbreviations and Definition of Terms 
Abbreviation 
Definition 
ACE 
Angiotensin converting enzyme 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
BDP 
Betamethasone dipropionate 
BSA 
Body surface area 
CAL 
Calcipotriene (United States term) / Calcipotriol (European Union term) 
CRO 
Contract Research Organisation 
DLQI 
Dermatology Life Quality Index 
eCRF 
Electronic case report form 
EQ-5D 
EuroQOL five dimensions 
EU 
European Union 
FDA 
Food and Drug Administration 
HIV 
Human immunodeficiency virus 
ICF 
Informed consent form 
ICH-GCP 
International Conference on Harmonisation-Good Clinical Practice 
IEC 
Independent Ethics Committee 
IP 
Investigational product 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IWRS 
Interactive web response system 
LOCF 
Last-observation-carried forward 
LSR 
Local skin reaction 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple imputation 
mPASI 
Modified Psoriasis Area and Severity Index 
NRI 
Non-responder imputation 
OTC 
Over the counter 
PGA 
Physician’s Global Assessment 
PP 
Per protocol 
PRO 
Patient reported outcome 
PTCS 
Psoriasis Treatment Convenience Scale 
PUVA 
Psoralen + ultraviolet A 


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Abbreviation 
Definition 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SGA 
Subject global assessment of disease severity 
SUSAR 
Suspected unexpected serious adverse reaction 
UBC  
United BioSource Corporation 
UPT 
Urine pregnancy test 
US  
United States 
UVA / UVB 
Ultraviolet A / ultraviolet B 
 


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1.0 
SYNOPSIS    
Trial Title: 
A Randomised, Multicentre, Investigator-Blind, Parallel-Group 
Trial to Evaluate the Efficacy and Safety of MC2-01 Cream 
Compared to Vehicle and Active Comparator in Subjects with 
Mild-to-Moderate Psoriasis Vulgaris 
Protocol Number: 
MC2-01-C7 
Sponsor:  
Drug Delivery Solutions Ltd (part of MC2 Therapeutics 
Development Phase: 
3 
Primary Objective: 
To evaluate the efficacy of MC2-01 cream compared to active 
comparator in subjects with psoriasis vulgaris. 
Secondary Objective: 
To characterise the safety profile of MC2-01 cream in subjects 
with psoriasis vulgaris. 
Trial Design: 
Randomised, 
investigator-blind, 
multicentre, 
vehicle 
and 
comparator-controlled, parallel-group, 3-arm trial. The trial will 
include a maximum 30-day screening period, an 8-week treatment 
period, and a 2-week post-treatment follow-up period. 
Planned Sample Size: 
A total of 476 subjects is planned to be randomised in a 3:1:3 ratio 
(MC2-01 cream: MC2-01 cream vehicle: active comparator).  
Under the assumptions of the trial and a sample size of N=204 per 
active treatment group, the power for each of the superiority 
comparisons of MC2-01 cream and active comparator to MC2-01 
cream vehicle with respect to Modified Psoriasis Area and Severity 
Index (mPASI) is more than 99%. Assuming that 30% of subjects 
treated with either MC2-01 cream or active comparator 
respectively, 11% of subjects treated with MC2-01 cream vehicle 
will have Physician’s Global Assessment (PGA) success, the 
power for the each of the superiority comparisons with respect to 
PGA success is 90.4%. 


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Trial Population: 
Generally healthy males or non-pregnant females, at least 18 years 
of age, with a clinical diagnosis of plaque psoriasis (psoriasis 
vulgaris) of at least 6 months duration that involves non-scalp 
regions of the body (trunk and/or limbs), with a PGA of disease 
severity of mild or moderate on the body (trunk and/or limbs) and 
an mPASI score of at least 3. 
Investigational 
Product(s): 
MC2-01 cream (calcipotriene (CAL) and betamethasone 
dipropionate (BPD), w/w 0.005%/0.064%). 
MC2-01 cream vehicle. 
Reference Product(s): 
Calcipotriene/betamethasone dipropionate gel/topical suspension, 
50 micrograms/g CAL (as monohydrate)/0.50 mg/g 
betamethasone (as dipropionate, equivalent to 0.64 mg/g BDP), 
approved in the European Union (EU) as Dovobet® 
Gel/Daivobet® Gel and in the US as Taclonex® Topical 
Suspension. For this phase 3 trial, the reference product will be 
sourced in EU as Daivobet® / Dovobet® Gel. 
Primary Endpoint: 
Percentage change from baseline in mPASI on the body (trunk 
and/or limbs) at Week 8. 
Secondary Endpoints: 
• PGA success on the body (trunk and/or limbs) at Week 8 
• Subject assessment of treatment convenience at Week 8 using 
the Psoriasis Treatment Convenience Scale (PTCS) Analysis of 
secondary endpoints 
Safety Endpoints 
• Local skin reaction; 
• AEs and serious adverse events (SAEs); 
• Changes in safety laboratory test results; 
• Changes in vital signs and physical examinations 


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PRO Endpoints: 
• Subject assessment of treatment convenience at Week 4 using 
the PTCS.  
• Change from Baseline in DLQI score at Week 4 and Week 8; 
• Change from Baseline in EQ-5D score at Week 4 and Week 8; 
Other Endpoints: 
• Percentage change from Baseline in mPASI on the body (trunk 
and/or limbs) at Week 4;  
• mPASI 75 (at least 75% reduction in mPASI from baseline) on 
the body (trunk and/or limbs) at Week 4 and Week 8; 
• Change from baseline in Subject global assessment of disease 
severity (SGA) at Week 4 and Week 8; 
• Change from baseline in PGA for the scalp at Week 4 and 
Week 8; 


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Statistical Methods: 
Primary endpoint 
The primary efficacy endpoint is the percentage change in mPASI 
the body (trunk and/or limbs) from baseline to Week 8.  
Superiority analysis 
First the percentage change in mPASI from baseline to Week 8 
for MC2-01 cream and the active comparator will be compared 
with that of MC2-01 cream vehicle for a superiority evaluation 
using the treatment-policy estimand for the Intent to treat (ITT) 
population and imputing missing data using multiple imputation 
(MI).  
The comparison will be done using an ANCOVA model 
including treatment, site, and baseline PGA as factors, and 
baseline mPASI as covariate. The estimated differences between 
MC2-01 cream and MC2-01 cream vehicle, and between active 
comparator and MC2-01 cream vehicle, will be reported together 
with the associated standard error, the 95% confidence interval, 
and a test corresponding to no difference between treatments. 
Non-inferiority analysis  
Next, if and only if superiority to MC2-01 cream vehicle can be 
claimed for both MC2-01 cream and active comparator on the 5% 
significance level, MC2-01 cream will be compared to active 
comparator for a non-inferiority evaluation using the treatment-
regimen estimand for the ITT population and imputing missing 
data using MI.   
Percentage change in mPASI from baseline to Week 8 will be 
compared between MC2-01 cream and active comparator for a 
non-inferiority evaluation using the -12 percentage points non-
inferiority margin. The comparison will be done using the same 
model as applied for the analysis of superiority vs. vehicle as 
described above: an ANCOVA model including treatment, site, 
and baseline PGA as factors, and baseline mPASI as covariate. 
The estimated difference between MC2-01 cream and active 
comparator will be reported together with the associated standard 


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error, and the 95% confidence interval. If the lower limit of the 
95% confidence interval is above -12 percentage points, non-
inferiority is demonstrated.   
Sensitivity analyses 
For the superiority analyses of MC2-01 cream and active 
comparator to MC2-01 cream vehicle, as well as for the non-
inferiority analysis of MC2-01 cream to active comparator, the 
below sensitivity analyses will be performed.  
Internal validity   
The primary analysis using MI assumes that data are missing at 
random within each treatment arm. For each hypothesis, the 
sensitivity of this assumption is investigated using a so-called 
tipping point analysis; a penalty (a number) is added to all imputed 
Week 8 values in the MC2-01 treatment group or (when testing 
superiority of active comparator vs. vehicle) in the active 
comparator group, and the analysis is repeated on the ITT 
population for the treatment-regimen estimand. The penalty d is 
gradually increased until the point, the tipping point, where the 
conclusion (superiority or non-inferiority depending on the 
analysis) no longer is demonstrated. If the tipping point is 
considered a clinical plausible difference, the tipping-point 
analysis does not support the primary analysis.  
External validity   
• The primary analysis is repeated using the hypothetical-
strategy estimand based on the ITT population and imputing 
missing data using MI.  
• The primary analysis using the treatment-policy estimand and 
imputing missing data using MI is repeated based on the PP 
population.  
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
• PGA success the body (trunk and/or limbs) at Week 8 


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• Subject assessment of treatment convenience at Week 8 using 
the PTCS 
Analyses of secondary endpoints 
To control the global Type-I error, the secondary endpoints will be 
tested in hierarchical order, if and only if non-inferiority can be 
demonstrated for the primary endpoint. The endpoints will be 
analyzed using the treatment-regimen policy estimand for the ITT 
population. 
For PGA success, missing PGA values will be imputed using MI 
considering PGA as a continuous endpoint. 
• PGA success: PGA success of both MC2-01 cream and active 
comparator will be compared with that of MC2-01 vehicle for 
a superiority evaluation. The comparison will be done using a 
logistic model with treatment, baseline PGA, and site as 
factors.  
• PGA success: Non-inferiority of MC2-01 cream versus active 
comparator. PGA success will be compared between MC2-01 
cream and active comparator for a non-inferiority evaluation 
using a -10 percentage points non-inferiority margin, as -10 
percentage point is considered the largest clinically acceptable 
loss of effect. This non-inferiority margin was also used in the 
MC2-01-C2 phase 3 clinical trial: A randomised, multicentre, 
investigator-blind, parallel-group trial to evaluate the efficacy 
and safety of MC2-01 cream compared to MC2-01 cream 
vehicle and active comparator in subjects with mild-to-
moderate psoriasis vulgaris (1). The percentage of subjects in 
each group with treatment success will be calculated along with 
its 95% confidence interval (CI) using normal approximation. 
A 95%, 2-sided CI for PM-PA, where PM and PA is the PGA 
treatment success rate at Week 8 for MC2-01 cream and active 
comparator respectively, will be computed using normal 
approximation using Proc FREQ with RISKDIFF option. 
MC2-01 will be considered non-inferior to active comparator 
if the lower bound of the 2-sided 95% CI is ≥ -10% points. 


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• PCTS: Superiority of MC2-01 cream versus active comparator. 
A PCTS score is considered invalid, if subject has discontinued 
study medication more than 7 days prior to the day of 
assessment. Missing and invalid PTCS scores will be imputed 
using the last valid measure prior to the visit (LOCF). This 
approach corresponds to a “PCTS while on treatment” 
estimand. The PCTS score will be compared between MC2-01 
cream and active comparator using an ANCOVA model with 
treatment, baseline PGA, and site as factors.  
• mPASI: In analogy with the analysis of the primary endpoint, 
superiority of MC2-01 cream versus active comparator will be 
evaluated using an ANCOVA model including treatment, site, 
and baseline PGA as factors, and baseline mPASI as covariate. 
Missing mPASI values will be imputed using MI. 
• PGA: Superiority of MC2-01 cream versus active comparator. 
PGA success will be compared between MC2-01 cream and 
active comparator using a logistic model with treatment, 
baseline PGA, and site as factors.  
Sensitivity analyses 
• For PGA success, a sensitivity analysis will be performed 
where missing values are imputed as non-responders (NRI). 
Another sensitivity analysis will be performed repeating the 
primary analysis for the hypothetical-strategy estimand based 
on the ITT population and imputing missing data using MI.  
• For PCTS the analysis will repeated for the PP population 
instead of the ITT population with the same imputation 
(LOCF).  
• For mPASI the same sensitivity analyses as for the primary 
endpoint will be performed.  
Trial Sites: 
Approximately 34 trial sites in EU 
Planned Dates of Trial: 
Trial initiation Q4, 2018 


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2.0 
INTRODUCTION   
2.1 
Background 
Psoriasis is a common, immune-mediated, inflammatory skin disease that is found world-wide. 
The prevalence of diagnosed psoriasis in the United States (US) is approximately 3%(2) whereas 
the prevalence in Europe varies anywhere from 0.6 to 6.5%(3) with an average of approximately 
3% (4). The clinical course is unpredictable but, in most cases, psoriasis is a chronically remitting 
and relapsing disease. Chronic stable plaque psoriasis (psoriasis vulgaris) is the most common 
form of the disease, accounting for 85-90 % of cases(5). Plaque-type psoriasis or psoriasis vulgaris 
is the most common form of the disease, and manifests as raised, red, scaly patches with silver 
scales. The lesions are usually distributed symmetrically and occur most commonly on the 
extensor parts of elbows and knees; scalp, lumbosacral region and umbilicus(6). Patients with 
psoriasis have reduced quality of life with reduced levels of employment and income(7), and 
studies have shown that patients with psoriasis are emotionally and physically impaired by their 
disease comparable to that seen with cancer, heart disease, rheumatoid arthritis, diabetes or 
depression(8, 9). 
Individuals with psoriasis appear to be at an elevated risk of developing other chronic and 
serious health conditions, such as metabolic syndrome/type 2 diabetes, cardiovascular disease, 
psoriatric arthritis and other chronic inflammatory diseases(10, 11). 
There is no cure for psoriasis. The goal of treatment is to reduce or eliminate its signs and 
symptoms. Mild to moderate disease is often treated with topical therapies. Among topical 
therapies, a combination treatment of a Vitamin D analog and a topical glucocorticosteroid has 
become especially popular. Several studies show that the combination of calcipotriol (CAL) and 
betamethasone dipropionate (BDP) is superior to each of the single agents(12-14).There is strong 
scientific rationale for the combination of vitamin D and glucocorticosteroids both with respect 
to efficacy and safety(15-17), and combination treatment with a Vitamin D analog and a topical 
corticosteroid is recommended in both European and American guidelines(18-20). 
CAL and BDP are incompatible in an aqueous environment, since CAL requires basic conditions 
to maintain stability while betamethasone requires acidic conditions. Currently marketed products 
are therefore restricted to non-aqueous, oil-based formulations. 
Sponsor has developed the MC2-01 cream containing the fixed dose combination 0.005 w/w% 
CAL (as anhydrate) and 0.064 w/w% BDP using the proprietary PADTM Technology which 
protects the drug substances from degradation during storage. The MC2-01 cream is easy to apply, 
and the cosmetic appearance is that of a white, easily-spreadable cream that absorbs completely 
into the skin a few minutes after application and it is expected that MC2-01 cream will differentiate 
from marketed formulations of CAL/BDP by patient preference for the cream. 


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2.2 
Rationale of the Trial 
In this trial, the MC2-01 cream will be compared with MC2-01 cream vehicle and the marketed 
product CAL/BDP combination gel/topical suspension, which is marketed under the brand name 
Dovobet® Gel/Daivobet® Gel in the EU and as Taclonex® Topical Suspension in the US. For this 
trial, the active comparator is sourced in the European Union (EU) as Daivobet® / Dovobet® Gel. 
This product is a liquid oil that contains the active ingredients CAL/BDP 
(calcipotriol/betamethasone dipropionate, 0.05/0.64 mg/g). This corresponds to 0.005% w/w 
calcipotriol and 0.064 % w/w (or 0.64 mg/g) betamethasone diproprionate, i.e. the same 
concentrations as in MC2-01 cream.  
The currently marketed CAL/BDP products are restricted to non-aqueous oil-based formulations 
that are sticky and inconvenient to many patients(21). The MC2-01 cream possesses superior 
cosmetic properties to most other topical formulations, and the purpose of the trial is to compare 
the clinical efficacy, safety, and convenience of the MC2-01 cream to the Daivobet ® / Dovobet® 
Gel. Treatment convenience evaluated using the Psoriasis Treatment Convenience Scale will be 
included as a secondary endpoint. 
The primary focus of this trial is psoriasis on the body (trunk and/or limbs). The rationale for 
including subject with psoriasis involving the scalp is to explore the efficacy of MC2-01 cream in 
scalp psoriasis. Psoriasis on scalp and body, respectively, are to be regarded as two separate 
treatment indications and the treatment effect are expected to differ.   
2.3 
Benefit-risk Assessment 
The subject population will be composed of subjects with mild to moderate psoriasis; their 
psoriasis is expected to be manageable with topical therapy.  
The active ingredients in the investigational products (CAL and BDP) are known to be effective 
for the treatment of psoriasis. The safety and efficacy profiles for marketed products with these 
ingredients (formulated as ointment, gel/topical suspension and more recently aerosol foam) are 
well known. A cream formulation of CAL and BDP may benefit subjects by providing improved 
convenience and ease of use resulting in increased patient adherence to therapy which will improve 
real-life treatment outcome (22). 
According to the SmPC for Daivobet gel, the common AE (>1%) is pruritus. Uncommon (i.e. 
≥0.1% and < 1%) AEs are folliculitis, skin infections, exacerbation of psoriasis, dermatitis, 
erythema, rash, skin irritation, skin burning sensation, application site pain, as well as eye irritation 
(probably related to use on scalp).  
The available data on MC2-01 cream suggest that MC2-01 cream will display a similar safety 
profile as the approved CAL/BDP topical products. A Phase 3 trial with MC2-01 cream and a 
maximal usage trial in adults have completed enrolment. As of the cut-off date of this clinical trial 


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protocol, the adverse event reported is as expected and no serious unexpected serious adverse 
reactions (SUSARs) have been reported.  
A subset of subjects will receive a cream vehicle. There is a risk that psoriasis symptoms may 
worsen in these vehicle-treated subjects; while an exacerbation of psoriasis may be inconvenient, 
it would not put the subjects at undue risk. In case of inadequate efficacy, the subject can decide 
to withdraw and then receive alternative therapy according to her/his choice. 
3.0 
TRIAL OBJECTIVES AND PURPOSE 
The primary objective is to evaluate the efficacy of MC2-01 cream compared to active comparator 
in subjects with psoriasis vulgaris. 
The secondary objective is to characterise the safety profile of MC2-01 cream in subjects with 
psoriasis vulgaris. 
4.0 
TRIAL DESIGN 
4.1 
Overall Trial Design 
This is a randomised, investigator-blind, multicentre, vehicle and comparator-controlled, parallel-
group, 3-arm trial. The trial will include a maximum 30-day screening period, an 8-week treatment 
period, and a 2-week post-treatment follow-up period.   
Trial subjects will be enrolled at approximately 34 investigative sites in the EU. Approximately 
476 subjects who meet the trial entry criteria will be randomly assigned in a 3:1:3 ratio to receive 
either MC2-01 cream, MC2-01 cream vehicle or active comparator. Subjects will apply trial 
medication to affected areas of the body (trunk and/or limbs) and, if applicable, scalp once daily 
for 8 weeks.  
The maximum trial duration for each subject will be approximately 14 weeks and includes a 
screening period of up to 30 days (if washout of prohibited medications is required), an 8-week 
treatment period, and a follow-up period of 2 weeks. The end of trial is defined as last subject last 
visit. 
After having provided written informed consent, the subject will undergo screening procedures. 
At the end of the screening period, eligible subjects will be randomly assigned to one of the trial 
treatment groups on Day 0 (Visit 1/Baseline) of the treatment period.  
During the treatment period, subjects will return to the trial site according to the trial schedule for 
interim efficacy assessments, and assessment of compliance with the treatment regimen, 
concomitant medications, and adverse events (AEs).  
The investigator will score the disease severity of the subject using mPASI, PGA, and body surface 
area (BSA) involvement; and the subject will perform a disease assessment using SGA. The 


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subjects will be asked to complete the Dermatology Life Quality Index (DLQI), EuroQOL five 
dimensions (EQ-5D), and the Psoriasis Treatment Convenience Scale questionnaires. Safety 
assessments (local skin reaction, AEs, laboratory tests, vital signs and physical examination) will 
be performed.  
The trial design is summarised in Figure 4-1. 
Figure 4-1  
Trial Design  
 
        
 
Screening Period 
 
8-Week Treatment Period 
 
 2-Week Follow-up Period* 
 
 
 
 
    
 
 
 
 
    Screening Period 
 
 
                        
 
 
 
 
 
 
 
 
 
 
 
 
Screening 
Up to Day -30 
Visit 0 
Baseline 
Day 0 
Visit 1 
Weeks 1, 2, 4, and 6 
Days 7, 14, 28, 42 (±2) 
Visits 2 - 5 
End of Treatment 
Week 8 
Day 56 (±2) 
Visit 6 
Follow Up 
Week 10 
Day 70 (±2) 
Visit 7 
 
*Follow-up visits will be required for subjects who have treatment related unresolved AEs or elevated albumin corrected serum 
calcium levels at Week 8. For all other subjects, telephone call 2 weeks after the Week 8 visit is sufficient. 
 
4.2 
Trial Endpoints 
Primary Endpoint 
• Percentage change from Baseline in mPASI on the body (trunk and/or limbs) at Week 8 
Secondary Endpoints  
• PGA success at Week 8, defined as a minimum 2-point decrease from Baseline to Week 8 on 
the PGA of disease severity on the body (trunk and/or limbs); i.e., a score of 0 (clear) or 1 
(almost clear) for subjects with moderate disease at Baseline; or a score of 0 (clear) for subjects 
with mild disease at Baseline. 
• Subject assessment of treatment convenience at Week 8 using the PTCS.   
MC2-01 cream (n= 204) 
Active comparator (n= 204) 
MC2-01 Vehicle cream (n= 68) 


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Safety Endpoints  
Safety endpoints include the following: 
• Local skin reaction; 
• AEs and serious adverse events (SAEs); 
• Changes in safety laboratory test results; 
• Changes in vital signs and physical examinations. 
Other Endpoints 
Efficacy 
• Percentage change from Baseline in mPASI score on the body (trunk and/or limbs) at Week 
4; 
• At least 75% reduction in mPASI from Baseline (mPASI 75) on the body (trunk and/or limbs) 
at Week 4 and Week 8;  
•  PGA success at Week 4, defined as a minimum 2-point decrease from Baseline to Week 4 on 
the PGA of disease severity on the body (trunk and/or limbs); i.e., a score of 0 (clear) or 1 
(almost clear) disease for subjects with moderate disease at Baseline; or a score of 0 (clear) 
for subjects with mild disease at Baseline.  
• Change from baseline in PGA on the scalp at Week 4 and Week 8  
• Change from Baseline in SGA at Week 4 and Week 8. 
Patient reported outcome  
• Subject assessment of treatment convenience at Week 4 using the PTCS.  
• Change from Baseline in DLQI score at Week 4 and Week 8; 
• Change from Baseline in EQ-5D score at Week 4 and Week 8; 
5.0 
SELECTION OF TRIAL POPULATION 
5.1 
Subject Population 
A total of 476 subjects will be enrolled. An individual subject will be allowed to participate in the 
trial one time only. A rationale for the choice of sample size is provided in Section 8.2 of this 
protocol. 


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Each potential subject will sign and date an informed consent document before any trial-specified 
procedures are performed. Subjects will provide authorisation for use of their personal data in 
accordance with the applicable regulations regarding privacy and data protection. 
5.2 
Inclusion Criteria 
Subjects must meet all the following criteria to be eligible for participation in the trial: 
1. 
Have provided written informed consent. 
2. 
Generally healthy males or non-pregnant females, of any race or ethnicity, who are at least 
18 years of age at the time of screening;  
3. 
Have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 6 months 
duration that involves the body (trunk and/or limbs) that is amenable to topical treatment 
with a maximum of 15 g of trial medication per day. 
4. 
Have a PGA of disease severity of mild or moderate on the body (trunk and/or limbs); 
5. 
Have an mPASI score of at least 3; 
6. 
Have a treatment area involving 2-30% of the body (trunk and/or limbs). For subjects 
with scalp psoriasis included in the treatment area, the total treatment area on body and 
scalp must not exceed 30%; 
7. 
Female subjects must be of either: 
• 
Non-childbearing potential, i.e., post-menopausal for at least 1 year or have a 
confirmed clinical history of sterility (e.g., hysterectomy or tubal ligation) or, 
• 
Childbearing potential with a negative urine pregnancy test prior to initiation of trial 
treatment, to rule out pregnancy.  
8. 
Female subjects of childbearing potential must have a negative urine pregnancy test result 
at Screening, and if sexually active they must agree to use a highly effective method of 
contraception (i.e. a method with a failure rate of less than 1% per year when used 
consistently and correctly) for one month prior to Visit 1 and until the follow-up visit has 
been performed. Highly effective contraception is defined as follows:  
• combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation: 
o oral 
o intravaginal 
o transdermal 
•  progestogen-only hormonal contraception associated with inhibition of ovulation: 
o oral 
o injectable 


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o implantable 
• intrauterine device (IUD) 
• intrauterine hormone-releasing system (IUS)  
• bilateral tubal occlusion  
• vasectomised partner (provided that is the sole sexual partner of the subject and that 
the vasectomised partner has received medical assessment of the surgical success.) 
• sexual abstinence (if in line with the preferred and usual lifestyle of the subject and 
defined as refraining from heterosexual intercourse during the entire period of the trial. 
Periodic methods of abstinence (e.g. calendar, ovulation, symptothermal, post-
ovulation methods) are not accepted methods of contraception.) 
5.3 
Exclusion Criteria 
Subjects who fulfil any of the following criteria will be ineligible to participate in the trial: 
1. 
Current diagnosis of unstable forms of psoriasis, including guttate, erythrodermic or 
pustular psoriasis;  
2. 
Other inflammatory skin disease in the treatment area that may confound the evaluation of 
the psoriasis vulgaris (e.g., atopic dermatitis, contact dermatitis, tinea corporis);  
3. 
Presence of pigmentation, extensive scarring, pigmented lesions or sunburn in the treatment 
areas, which could interfere with the rating of efficacy parameters;  
4. 
Planned excessive or prolonged exposure to either natural or artificial sunlight, including 
tanning booths, sun lamps, etc; 
5. 
History of hypersensitivity to any component of the test product or reference product;  
6. 
Current or past history of hypercalcemia, vitamin D toxicity, severe renal insufficiency, or 
severe hepatic disorders; 
7. 
Females who are pregnant, breast feeding, or planning a pregnancy;  
8. 
Systemic treatment with biological therapies, whether marketed or not, with a possible 
effect on psoriasis vulgaris within the following time periods prior to Visit 1/Baseline and 
during the trial: 
• Etanercept – within 4 weeks prior to Visit 1/Baseline, 
• Adalimumab, Alefacept, Infliximab – within 8 weeks prior to Visit 1/Baseline, 
• Ustekinumab – within 16 weeks prior to Visit 1/Baseline, 
• Other products – within 4 weeks/5 half-lives prior to Visit 1/Baseline (whichever was 
longer). 
In general, patients who are candidates for biological or other systemic therapy are 
excluded from the trial. 


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9. 
Use of systemic treatments that suppress the immune system (fumaric acid, methotrexate, 
retinoids, PDE4 inhibitors, corticosteroids (excluding inhaled, nasal, auricular or ocular 
corticosteroids), ciclosporin (cyclosporine), and other systemic chemotherapeutic 
antineoplastic therapy) within 4 weeks prior to Visit 1/Baseline and during the trial;    
10. Use of phototherapy (psoralen + ultraviolet A radiation [PUVA] and ultraviolet B radiation 
[UVB]) within 4 weeks prior to Visit 1/Baseline and during the trial; 
11. Use of topical treatments (e.g., corticosteroids (Class 1, 2 and 3), vitamin D analogs, 
retinoids, PDE4 inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar), except 
for emollients and non-medicated shampoos, with a possible effect on psoriasis within 2 
weeks prior to Visit 1/Baseline.  
Glucocorticoids Class 4 (e.g. clobetasol propionate) are prohibited within 4 weeks prior to 
Visit 1/baseline. Subjects using glucocorticoids Class 4 may have their treatment 
switched to glucocorticoids Class 1-3. However, the treatment must be stopped at least 2 
weeks prior to Visit 1/Baseline (refer to Appendix 3 
Classification of Topical Corticosteroids).  
12. Presence of infections in the treatment area (e.g. skin infection with bacteria (including 
tuberculosis), viruses, parasites or fungi) or skin manifestations of atrophic skin, atrophic 
striae, skin vein fragility, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and wound 
in the treatment; 
13. Known Human Immunodeficiency Virus (HIV) infection 
14. Have any chronic or acute medical condition that, in the opinion of the investigator, may 
pose a risk to the safety of the subject, or may interfere with the assessment of safety or 
efficacy in this trial; 
15. Require the use of any concomitant medication that, in the investigator’s opinion, has the 
potential to cause an adverse effect when given with the investigational product (IP) or will 
interfere with the interpretation of the trial results; 
16. Initiation of, or expected changes to, concomitant medication that may affect psoriasis (e.g., 
beta-blockers, chloroquines, lithium, and angiotensin converting enzyme [ACE] 
inhibitors); 
17. Participation in another clinical trial or received an investigational product or non-marketed 
drug substances within 30 days prior to screening. 
18. In the opinion of the investigator, the subject is unlikely to comply with the clinical trial 
protocol 
5.4 
Withdrawals and Discontinuation of Treatment 
In accordance with legal requirements and International Conference on Harmonisation (ICH) – 
Good Clinical Practice (GCP) guidelines, every subject has the right to refuse further participation 
in this trial at any time and without providing reasons (see also Section 9.2). A subject's 
participation is to be terminated immediately upon his/her request.  The investigator should seek 
to obtain the reason and record this on the electronic case report form (eCRF) whenever possible. 


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If, at the time of refusal, a trial product has already been administered, the subject should be 
advised to have an Early Termination visit performed and follow up on treatment related AEs.  
If a subject wants to discontinue from the trial, for example due to lack of time, efforts will be 
made to complete a final evaluation at Week 8 if possible.  
The reasons for discontinuation of treatment may be among others:  
• Inconsistency with inclusion/ exclusion criteria.  
The investigator should use his/her discretion to determine if there is a safety concern related 
to continued treatment with trial medication, or if the subject may continue treatment. For 
example, if a subject incorrectly is enrolled in the trial with a mPSAI of 1,8, the treatment 
with the IP should not be discontinued. This event should be reported as a Protocol Deviation 
• Intake of a prohibited medication(s).  
The investigator should use his/her discretion to determine if there is a safety concern with 
the combined treatment or the subject may continue treatment with the IP. For example, if 
the subject has applied salicylic acid cream on the treatment area, the treatment with the IP 
should not be discontinued. The subject should be advised to stop the treatment and the event 
should be reported as a Protocol Deviation. 
• AE/SAE.  The investigator should use his/her discretion to determine if the subject should 
continue treatment with the IP.  
Subjects discontinued treatment due to a treatment-related AE will be monitored until the AE 
is resolved or until the medical condition of the subject is stable.  
• Pregnancy  
• Investigator’s discretion 
• Lost to follow-up 
If the IP application is discontinued, the subject should be encourage to continue in the trial or at 
least come for the Week 8 visit. 
In addition, Regulatory Authority and MC2 reserves the right to end or suspend the trial at any 
time (see Section 9.2). 
5.5 
Replacement Policy 
Subjects who prematurely discontinue the trial after randomisation will not be replaced. 


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6.0 
TRIAL TREATMENTS 
6.1 
Investigational Product  
6.1.1 
MC2-01 cream 
MC2-01 cream is a combination product, CAL and BDP, administered as a cream formulation for 
topical administration. The MC2-01 cream is currently not a marketed product, which means that 
the product is still being tested and is not approved for sale. One concentration of the trial product 
will be studied: calcipotriol (50 micrograms) and betamethasone (0.64 mg/g). The list of inactive 
ingredients present in MC2-01 cream is presented in the Investigator Brochure(23). 
6.1.2 
MC2-01 cream vehicle 
The MC2-01 vehicle cream will contain the same ingredients as the active formulation without the 
active ingredients(23).  
6.1.3 
Active Comparator Product 
The active comparator is a marketed CAL/BDP gel/topical suspension, 50 micrograms/g CAL (as 
monohydrate)/0.50 mg/g betamethasone (as dipropionate, equivalent to 0.64 mg/g BDP), approved 
in the EU as Dovobet® Gel/Daivobet® Gel(24) and in the US as Taclonex® Topical Suspension(25). 
For this phase 3 trial, the reference product will be sourced in Europe as Daivobet® / Dovobet® 
Gel.  
The CAL/BDP gel/topical suspension contains the following inactive ingredients: Paraffin, liquid; 
polyoxypropylene stearyl ether; castor oil, hydrogenated; butylhydroxytoluene (E321); All-rac-
alpha-tocopherol.  
6.2 
Dosing Regimen 
Subjects must apply the trial product topically once daily preferable in the evening for 8 weeks to 
affected areas on the following body locations:  
• trunk (including the neck)  
• limbs, i.e., arms (including the back of the hands) 
• legs (including the buttocks and the top of the feet) and  
• scalp.  
The face, genitals and intertriginous areas should not be treated with the IP.  
Only affected areas are to be treated.  
Subjects are to record the date and time of application in the subject diary.  


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The subject should apply enough IP to treat the entire affected areas and rub in gently to ensure 
that the plaques are saturated with the medication. Up to 4 tubes/bottles of 60 gram will be 
dispensed for a treatment period of 2 weeks including the allowed visit window of 2 days. The 
weekly dose is not to exceed 100 g, and the treated area should not exceed 30% of the BSA. 
Subjects will be instructed that preferably no trial product should be applied within 4 hours of on-
treatment trial visits. 
In case an AE reported in one area of the body lead the investigator to the decision to discontinue 
treatment this will apply for treatment in general and not only to the area for which the AE was 
reported.  
Detailed application instructions will be provided in the subject instructions.   
6.3 
Dose Modification 
Subjects classified as clear at any of the on-treatment visits may stop the IP treatment at the 
investigator’s discretion. They should remain in the trial and attend all visits up to and including 
the follow-up visit. The IPs will continue to be dispensed to the subject, and IP treatment may be 
restarted at the subject’s discretion. The subjects should not discontinue IP treatment themselves 
between visits but is only allowed to stop using the IP treatment on the advice of the investigator 
at a scheduled visit. 
6.4 
Packaging, Labeling, Storage and Destruction 
Medication labels for the IPs will comply with the legal requirements of the country where the 
trial is performed and be printed in the local language.  
The IPs will be supplied by the MC2’s designated vendor and stored securely at the site under 
the control of the investigator. The temperature will be monitored and documented.    
The MC2-01 cream and MC2-01 cream vehicle will be supplied to the pharmacy/clinical site(s) 
as tubes containing 60 g of product. The MC2-01 cream and MC2-01 cream vehicle is to be 
protected from light and stored at a temperature of 2°- 8°C at the site. After dispensing to the 
subject, the MC2-01 cream can be stored for up to 8 weeks below 25°C.  
All medication – unused and used - will be returned for reconciliation and destruction.      
The active comparator will be supplied to the clinical site(s) as bottles containing 60 g of product. 
The active comparator is to be protected from light and stored below 25°C, however the product 
must not be refrigerated. 


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6.5 
Assignment to Treatment 
6.5.1 
Randomisation 
Randomisation will be performed using a validated system that automates the random assignment 
of treatment groups to randomisation numbers. Treatment assignment will be via a central 
interactive web response system (IWRS) in accordance with a pre-planned computer-generated 
randomisation schedule in a 3:1:3 ratio (MC2-01 cream; MC2-01 vehicle; active comparator). 
Randomisation will be stratified by trial site to ensure a proper distribution into the three treatment 
arms. Furthermore, on a country level, it will be ensured that up to 30 % of the population can be 
subjects with mild disease (based on the PGA), as monitored by data management. 
Randomisation data will be kept strictly confidential, accessible only to authorised persons not 
otherwise involved in the conduct of the trial, until the time of un-blinding. 
A subject who fulfils the trial eligibility requirements will be randomly assigned to treatment. 
6.5.2 
Blinding 
Due to difference in formulation and packaging, it is not possible to double blind the IPs. However, 
several precautions will be taken to maintain the blind to the extent possible. To keep the trial 
investigator blinded, packing and labelling of the outer box will be identical for all IPs. Due to 
different formulations, the IPs will be either packed in bottles (active comparator) or in tubes 
(MC2-01 cream and MC2-01 cream vehicle). Handling of individual bottles/tubes of IPs (e.g., 
dispensing, returning, drug accountability and weighing) will therefore be handled by a designated 
third person. Individual bottles/tubes of IPs will be inaccessible to the investigator(s) and other 
trial staff involved in the evaluation of subjects. Subjects will be instructed not to reveal the 
formulation of the IPs to the trial investigator. 
For details of the procedure for un-blinding of individual subjects in cases of emergency see 
Section 13.1.   
6.6 
Prior, Concomitant, and Prohibited Therapy 
All medications, including over-the-counter (OTC) drugs and vitamins, herbal and dietary 
supplements, taken within 30 days prior to the start of the trial will be recorded at Screening. 
Thereafter, a record of all medications and supportive therapy taken during the course of the trial 
will be made. Information regarding the total daily dose, route of administration, start and 
discontinuation dates, and indication are to be recorded on the subject’s eCRF. 
6.6.1 
Washout of prohibited medications prior to enrolment 
If a washout period is necessary due to treatment with any medication specified in the exclusion 
criteria (see Section 5.3), the washout period must be completed within 30 days prior to baseline.  


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6.6.2 
Prohibited medications during the trial 
Use of any medication that would exclude the subject from participation in the trial (as specified 
in Section 5.3 Exclusion Criteria) is also prohibited during the treatment and follow-up periods, 
which includes medications in the following categories:  
• Use of biological therapies with, whether marketed or not, with a possible effect on psoriasis;  
• Use of systemic treatments with a possible effect on psoriasis (e.g., fumaric acid, 
methotrexate, retinoids, PDE4 inhibitors, corticosteroids (excluding inhaled, nasal, auricular 
or ocular corticosteroids), ciclosporin (cyclosporine), and other systemic chemotherapeutic 
antineoplastic therapy). 
• Use of phototherapy (PUVA and UVB). 
• Use of topical treatments with a possible effect on psoriasis (e.g., corticosteroids, vitamin D 
analogs, retinoids, PDE4 inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar). 
• Initiation of dosing or changes in dosage of drugs that are known to have an effect on 
psoriasis should be avoided. This includes, but is not limited to, beta-blockers, chloroquines, 
lithium, and ACE inhibitors. 
• Emollients on the psoriasis affected areas on body (trunk and/or limps) and scalp 
6.6.3 
Allowed treatment outside the treatment area  
Subjects may receive laser treatment and use an emollient on the face, skin folds, and genital skin. 
Topical products (incl. products containing urea) that do not contain medication with antipsoriasis 
effect (e.g. vitamin D, glucocorticoids or calcineurins) are allowed on skin areas but not within 2 
cm of skin areas treated with trial medication.   
6.7 
Treatment Compliance 
Records of trial product used, and dosages administered will be kept during the trial. 
At all on-treatment visits, the subject will be asked if he/she has used the medication as prescribed. 
If this is not the case, the degree and nature of noncompliance will be collected in the CRF. In 
addition, subjects will be asked to complete a dosing diary during the treatment period as a measure 
of treatment compliance. Subjects who are noncompliant will be counseled. 
Subjects will be asked to return all used and unused tubes/bottles in the outer box at each visit. All 
returned tubes/bottles that had been dispensed to a subject and are returned with a broken seal will 
be weighed to determine the amount of the IP used per treatment phase.  
 
 


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7.0 
VISIT SCHEDULE AND ASSESSMENTS 
Table 7-1 Visit Schedule 
Visit 
Screening/ 
Visit 0a 
Visit 1 
Visit 
2 
TC 
(Visit 
3)  
Visit 
4 
Visit 
5 
Visit 
6 
/ETb 
Follow Up, 
Visit 7c 
 
 
Week 0 
Week 
1 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
Week 10 
 
Up to 
Day -30 
Day 0 
Day 
7±2 
Day 
14±2 
Day 
28±2 
Day 
42±2 
Day 
56±2 
Day 70±2 
Informed consentd 
X 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
[X] 
X 
 
 
 
 
 
 
Demographics, 
medical history 
X 
 
 
 
 
 
 
 
Prior and concomitant 
medication 
X 
X 
X 
 
X 
X 
X 
X 
Concurrent diagnoses 
X 
 
 
 
 
 
 
 
Physical Examination  
X 
X 
 
 
X 
 
X 
 
Vital signs  
 
X 
 
 
X 
 
X 
 
Urine pregnancy teste 
X 
X 
 
 
X 
 
X 
 
Laboratory 
assessments  
 
Xf 
 
 
Xf 
 
Xf 
Xf 
SGA  
 
X 
X 
 
X 
X 
X 
 
DLQI questionnaire 
 
X 
X 
 
X 
 
X 
 
EQ-5D questionnaire 
 
X 
 
 
X 
 
X 
 
Psoriasis Treatment 
Convenience Scale  
 
 
X 
 
X 
 
X 
 
PGA scoring 
[X] 
X 
X 
 
X 
X 
X 
 
mPASI scoring 
[X] 
X 
X 
 
X 
X 
X 
 
BSA  
[X] 
X 
 
 
X 
 
X 
 
Randomisation 
 
X 
 
 
 
 
 
 
Dispensing of IP and 
Diary 
 
X 
X 
 
X 
X 
 
 
Return of IP and Diary 
 
 
X 
 
X 
X 
X 
 
Compliance 
 
 
X 
X 
X 
X 
X 
 
Local skin reactions 
 
X 
X 
 
X 
X 
X 
 
Photographs 
 
X 
X 
 
X 
X 
X 
 
AE(s)g 
 
X 
X 
X 
X 
X 
X 
X 


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TC = telephone call; ET = early termination; PGA = physician’s global assessment;  
mPASI = modified Psoriasis Area and Severity Index; BSA= Body Surface Area; SGA = 
subject’s global assessment; DLQI= Dermatology Life Quality Index; EQ-5D = EuroQOL five 
dimensions questionnaire, IP = investigational product; AE = adverse event. 
 
a) A washout period of up to 30 days must be completed if the subject has been treated with 
anti-psoriatic treatments or other relevant medication, as defined by exclusion criteria. Items 
denoted in [brackets] must be reviewed at Visit 0/Screening prior to commencing a 
washout, to assess if the subject is otherwise eligible. Such items must be checked for any 
change in eligibility status at Visit 1/Baseline after the washout is completed. In case no 
washout is needed, the Screening Visit and Visit 1 may be performed on the same day. 
b) Procedures for subjects who withdraw from the trial before Visit 6/Week 8. 
c) An on-site follow-up visit after Week 8 is required to check: abnormal, elevated albumin 
corrected serum calcium or unresolved treatment related AEs. Treatment-related AEs will 
be monitored until the AE is resolved or until the medical condition of the subject is stable.  
For all other subject’s telephone call 2 weeks after the Week-8 visit to follow-up is 
sufficient.   
d) Informed consent must be signed both by subject and investigator before any trial related 
procedures are carried out. For subjects requiring a washout period, informed consent must 
be completed prior to washout. 
e) For female subjects of childbearing potential. If there is a suspicion of pregnancy at any 
time during the trial, a urine sample will be obtained and tested. 
f) If a laboratory result is abnormal and judged as clinically significant, the investigator must 
follow-up as clinically appropriate (this may involve requesting repeat samples). 
g) AEs are to be collected from the date of signing the informed consent, i.e. also during the 
washout period.   
 
 


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7.1 
Demographics and Medical History 
The following demographic and medical history must be collected:  
• Year of birth 
• Sex 
• Race 
• Ethic origin 
• Complete skin disease history  
• The year diagnosed with psoriasis vulgaris. If diagnosis is within the ongoing and 
preceding year, also month should be collected 
• All other current and past medical/surgical conditions within the previous 12 months. 
The Fitzpatrick skin type will be assessed according to the classification scheme in Table 7-2. 
Table 7-2 Fitzpatrick Skin Type Classification 
I 
Pale white skin, blue/hazel eyes, blond/red 
hair 
Always burns\does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
  
7.2 
Prior and Concomitant Medication 
Review and record prior medication and concomitant medication. 
All medications, including OTC drugs, herbals, vitamins, dietary supplements etc., taken within 
30 days prior to the start of the trial will be recorded at Screening. Thereafter, a record of all 
medications and supportive therapy taken during the trial will be made. Information regarding the 
total daily dose, route of administration, start and discontinuation dates, and indication are to be 
recorded on the subject’s eCRF. 
7.3 
Concurrent diagnoses   
Concurrent diagnoses must be collected as specified in the visit schedule (Table 7-1). 


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7.4 
Physical Examination 
An abbreviated physical examination including general appearance, regional lymph nodes and a 
complete dermatological examination of the skin must be performed, including height and weight 
at Visit 1/Day 0. The height and weight can be self-reported.  
7.5 
Vital Signs 
Blood pressure and pulse rate will be taken with the subject in the sitting position with 
approximately 5 minutes rest prior to measurement. Body temperature (oral or ear) will be also be 
measured. 
7.6 
Pregnancy Test 
Female subjects of child-bearing potential will undergo a routine urine pregnancy test (UPT) at 
the Visit 0/Screening before any trial-specific procedures are performed. The pregnancy test will 
be performed at the site using a urine dipsticks analysis. If the UPT is positive, the subject will not 
be permitted to enroll in the trial.  
During the course of the trial, urine pregnancy tests will be performed as specified in the visit 
schedule (Table 7-1). At the investigator’s discretion, additional testing for pregnancy may be 
performed for verification purposes. If there is a suspicion of pregnancy at any time during the 
trial, a urine sample will be obtained and tested. Should a subject become pregnant during the trial, 
treatment must be discontinued. Refer to Section 7.10.7 for additional information. 
Instruct all female subjects of childbearing potential to use approved form(s) of contraception.  
7.7 
Laboratory Assessments 
Blood and urine samples will be collected for routine safety laboratory tests as specified in the 
visit schedule (Table 7-1). Clinical laboratory specimens will be analyzed by a central licensed 
and accredited laboratory facility according to the laboratory’s standard operating procedures.  
7.7.1 
Biochemistry and Urinalysis  
For all subjects, the following tests will be performed as specified in the visit schedule (Table 7-1): 
• Serum biochemistry: serum calcium (albumin corrected), serum albumin, serum alkaline 
phosphatase, serum phosphate, plasma parathyroid hormone. 25-OH Vitamin D, only at Visit 
1. 
• Urinalysis: urinary calcium, urinary phosphate, urinary calcium:creatinine ratio. 
• Pregnancy testing:  all female subjects of child-bearing potential will undergo urine 
pregnancy testing as specified in Section 7.6. 
The investigator may collect additional blood samples to repeat any laboratory test that is abnormal 
post-dosing and is considered clinically significant. Abnormal laboratory results at the last 


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scheduled visit may require additional collection of samples on an “as needed” basis until: a) the 
values return to the baseline value, b) the values are within normal limits, c) the values are 
clinically stable, or d) the investigator determines that further follow-up is unnecessary. The 
investigator will record the date and time of all additional samples collected. If the investigator 
establishes a clear explanation for the laboratory abnormality, he or she will record this explanation 
in the eCRF. 
Abnormal clinically significant findings as determined by the Investigator will be reported as 
medical history if detected at Visit 1. At subsequent visits, any new abnormal clinically significant 
finding as determined by the Investigator will be reported as an AE. 
If albumin-corrected serum calcium is above the reference range at the last on-treatment visit, a 
follow-up test must be performed. 
7.8 
Investigator Assessments 
The investigator assessments are to be performed by a dermatologist or a physician with at least 
1 year of experience in dermatology. For physicians who do not fulfill the requirement regarding 
dermatological experience, the person must be preapproved by the sponsor. Preferably the same 
investigator will assess the subject throughout the trial. The assessments are to be performed as 
specified in the visit schedule Table 7-1. 
7.8.1 
Body surface area (BSA) involvement of psoriasis vulgaris on the body  
The total psoriatic involvement on the body and scalp will be recorded as a percentage of the total 
BSA, estimating that the surface of the subject’s full, flat palm (including the five digits) correlates 
to approximately 1% of the total BSA.  
The investigator will assess: 
• the extent of the subject’s psoriatic involvement on the body (excluding scalp, face, genitals, 
and intertriginous areas).  
• the extent of the subject’s psoriatic involvement on the scalp. 
7.8.2 
Modified Psoriasis Area and Severity Index (mPASI) 
At all on site visits, the investigator will assess the extent and severity of the subjects’ psoriasis on 
the body (trunk and/or limbs) (i.e. the scalp is not involved in this assessment) using an mPASI 
scoring system.  
The extent of psoriatic involvement (extent (E)) will be recorded for each of the 3 areas (arms, 
trunk, and legs) using the following scale: 


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0  =  no involvement 
1  =   < 10% 
4  =  50% - 69% 
2  =  10% - 29% 
5  =  70% - 89% 
3  =  30% - 49% 
6  =  90% - 100% 
 
The severity of the psoriatic lesions in each of the 3 areas will be recorded for each of the signs of 
redness, thickness, and scaliness. For each clinical sign, a single score, reflecting the average 
severity of all psoriatic lesions on given body region, will be determined according to the scale 
below:  
Redness 
0 
= 
none (no erythema) 
1 
= 
mild (faint erythema, pink to very light red) 
2 
= 
moderate (definite light red erythema) 
3 
= 
severe (dark red erythema) 
4 
= 
very severe (very dark red erythema) 
 
Thickness 
0 
= 
none (no plaque elevation) 
1 
= 
mild (slight, barely perceptible elevation) 
2 
= 
moderate (definite elevation but not thick) 
3 
= 
severe (definite elevation, thick plaque with sharp edge) 
4 
= 
very severe (very thick plaque with sharp edge) 
 
Scaliness 
0 
= 
none (no scaling) 
1 
= 
mild (sparse, fine-scale lesions, only partially covered) 
2 
= 
moderate (coarser scales, most of lesions covered) 
3 
= 
severe (entire lesion covered with coarse scales) 
4 
= 
very severe (very thick coarse scales, possibly fissured) 
The m-PASI is calculated from the scores given by the (sub)investigator during their assessment 
of the extent and severity of the disease by use of the following equation: 
Arms 0.2 (R + T + S) E = X  
Trunk 0.3 (R + T + S) E = Y  
Legs 0.4 (R + T + S) E = Z 
Where: R = score for redness; T = score for thickness; S = score for scaliness; E = score for extent. 
The sum of X + Y + Z equals the m-PASI score resulting in a minimum score of 0 and a maximum 
score of 64.8. 


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7.8.3 
Physician’s global assessment of psoriasis severity 
The Physician’s Global Assessment (PGA) measures the investigator’s impression of the disease 
at a single point using a defined, 5-point, static PGA scale (clear, almost clear, mild, moderate or 
severe); see Table 7-3.  
The PGA assessment should be made separately for the body (trunk and/or limbs) and the scalp. 
The PGA assessment will represent the average lesion severity on the two body locations. The 
assessments will be based on the condition of the disease at the time of evaluation, and not in 
relation to the condition at a previous visit. 
Table 7-3 Physician’s Global Assessment (PGA) 
Score 
Grade 
Definition 
0 
Clear 
Plaque thickening = no elevation or thickening of normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red colouration but post-inflammatory 
hypo or hyperpigmentation may be present) 
1 
Almost 
clear 
Plaque thickening = none or possible thickening but difficult to ascertain 
whether there is a slight elevation above normal skin level 
Scaling = none or residual surface dryness and scaling 
Erythema = light pink colouration 
2 
Mild 
Plaque thickening = slight but definite elevation 
Scaling = fine thin scales partially or mostly covering lesions 
Erythema = light red colouration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = coarse scale layer at least partially covering most lesions 
Erythema = definite red colouration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with hard or 
sharp edges 
Scaling = non-tenacious or thick tenacious scale predominates, covering most 
or all of the 
lesions 
Erythema = very bright red colouration, extreme red coloration or deep red 
coloration 
 
7.8.4 
Local skin reactions 
The local skin reaction assessment involves signs assessed by the investigator.  


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The investigator will assess the treatment area and/or immediate surrounding for the following 
identified signs:  
• Perilesional erythema, scaling, edema, atrophy, vesicles and erosion/ulceration;  
• Lesional vesicles, and erosion/ulceration.  
The intensity of each local skin reaction category is to be graded according to the scale in  
Table 7-4. The most severe intensity observed for each category of the local skin reaction 
assessment is to be recorded. 
Table 7-4 Local Skin Reaction Scores 
Investigator assessment of the lesional area 
 
0 (absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erosion/ulceration 
in lesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
Vesicles 
in lesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Investigator assessment of the perilesional area 
 
0=absent 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erythema  
in perilesional area 
None 
Barely visible 
erythema 
Distinct erythema 
Dark red erythema 
Scaling 
in the perilesional area 
None 
Barely visible 
scaling 
Distinct scaling 
Gross scales 
Edema 
in perilesional area 
None 
 barely palpable 
swelling 
Easily palpable 
swelling 
Gross swelling 
Atrophy 
in perilesional area 
None 
Barely visible 
thinning 
Distinct thinning 
Striae 
Vesicles  
in perilesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Erosion/ulceration 
in perilesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
 


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7.9 
Patient Reported Outcomes (PROs) 
The PRO instruments must be completed by the subjects before any other assessments are 
performed. The PRO assessments are to be performed as specified in the visit schedule  
(Table 7-1).   
7.9.1 
Subject Global Assessment of disease severity (SGA) 
Subjects will grade the overall severity of their symptoms according to the following 5-point scale: 
0  =  Clear; no psoriasis symptoms at all. 
1  =  Very mild; very slight psoriasis symptoms that do not interfere with daily life.  
2  =  Mild; slight psoriasis symptoms that interfere with daily life only occasionally.  
3  =  Moderate; definite psoriasis symptoms that interfere with daily life frequently.  
4  =  Severe; intense psoriasis symptoms that interfere or restrict daily life very frequently. 
7.9.2 
Dermatology Life Quality Index (DLQI) 
The DLQI(26) is a validated questionnaire consisting of 10 questions relating to the degree to 
which the subject’s skin condition affected their daily activities.  
7.9.3 
EuroQOL five dimensions questionnaire (EQ-5D) 
The EQ-5D is one of the most commonly used generic questionnaires to measure health-related 
quality of life (QOL)(27). It consists of a questionnaire and a visual analog scale (EQ-VAS). The 
EQ-VAS records the subject’s perceptions of their own current overall health and can be used to 
monitor changes over time. The self-assessment questionnaire is a self-reported description of the 
subject’s current health in 5 dimensions i.e., mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression. 
7.9.4 
The Psoriasis Treatment Convenience Scale 
The Psoriasis Treatment Convenience Scale must be completed by the subjects before any other 
assessments are performed. The assessments are to be performed as specified in the visit schedule 
(see Table 7-1).  
The aim of the Psoriasis Treatment Convenience Scale is to assess the impact and convenience of 
psoriasis treatment. The scale has been tested for content validity through focus group interview 
with 20 patients and adapted based on the responses. The scale consists of 6 disease-specific, self-
report questions with a recall period of 1 week and rated on a 1-10 point scale.  
1. How easy was the treatment to apply to the skin?   
2. How greasy was the treatment when applying it to the skin? 
3. How moisturised did your skin feel after applying the treatment? 
4. How greasy did your skin feel after applying the treatment? 


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5. How much did treating your skin disrupt your daily routine? 
6. Overall, how satisfied were you with the medical treatment? 
7.9.5 
Photography 
Colour photographs of the treatment area should be taken as specified in the visit schedule (see 
Table 7-1).  
MC2 may at its discretion use the photographs in publication or similar types of information 
material for health care professionals. The photographs can also be part of the training material 
used for training and educational purposes. Use of photographs for these purposes is optional and 
requires prior consent by the subject.   
MC2 will ensure that all necessary steps to ensure the anonymity of the subject are taken (e.g. 
masking of face, no photos of characteristic details on the body, etc. 
7.10 
Adverse Events 
7.10.1 
Adverse events assessments 
The investigator is responsible for obtaining, assessing, and documenting all AEs during the trial. 
Adverse Events information will be collected from the time of the signature of the informed 
consent form and first trial-related activity performed until the end of the trial. An AE is an 
untoward medical occurrence in any subject during the trial which does not necessarily have a 
causal relationship with the IP.  
All AEs will be documented in the eCRF, including a description of each AE, AE relationship to 
IP administration, start and stop dates, seriousness, severity, action taken and outcome.  
Any AE that meet the serious criteria must be reported on the eCRF and on a separate SAEs report 
form. SAEs must be reported immediately to MC2 or designee as soon as it becomes known to the 
investigator and not later than within 24 hours of his/her knowledge of the occurrence of an SAE.  
Throughout the trial, the occurrence of AEs should be sought by nondirective questioning of the 
subject at each visit during the trial. Information on AEs can also be obtained from signs and 
symptoms detected during examination, observations made by the trial site personnel, or 
spontaneous reports from subjects. Pre-existing conditions that worsen during the trial should also 
be recorded as AEs. This will also include worsening of the psoriasis vulgaris as judged by the 
investigator. 
AEs requiring therapy must be treated with recognised standards of medical care to protect the 
health and well-being of the subject. Treatment due to an AE will be recorded in the subject’s 
records and on the appropriate eCRF. 


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Any AE that is considered related to the IP must be followed by the investigator until it is resolved 
or until the medical condition of the subject is stable; all relevant follow-up information will be 
reported to MC2 or designee. 
The outcome of an AE will be classified as recovered, recovered with sequelae, 
recovering/resolving, ongoing, or death. 
7.10.2 
Timing 
AEs will be collected during the period from the time of the signature of the informed consent 
form and first trial-related activity performed until the end of the trial.  
7.10.3 
Severity of adverse events 
The investigator is to classify the severity (intensity) of an AE according to the following 
definitions: 
• Mild – The subject was aware of the signs and symptoms, but the signs and symptoms were 
easily tolerated and do not interfere with daily activity. 
• Moderate – The signs and symptoms were sufficient to restrict, but did not prevent, usual daily 
activity for the subject. The subject is still able to function.  
• Severe – The subject was unable to perform usual daily activity. 
The maximum intensity of an AE (mild, moderate, or severe) will be assessed taking into 
account the possible range of intensity of the symptom(s). 
7.10.4 
Relationship of an adverse event to trial treatment 
The investigator is responsible to assess the relationship of an AE to the IP treatment using good 
clinical judgment and the following definitions: 
Not Related 
The AE is clearly explained by another cause not related to the IP 
administration; the temporal relationship of the AE to IP administration 
makes a causal relationship unlikely, or, concomitant medication, 
therapeutics interventions, or underlying condition provide a sufficient 
explanation for the observed AE 
Possibly Related 
The AE and administration of IP are temporally related, but the AE can 
be explained equally well by causes other than the IP administration 
Probably Related 
The AE and use of IP are temporally related, and the AE is more likely 
explained by IP administration than by other causes 


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Definitely Related 
The AE and IP administration are related in time, and a direct 
association can be demonstrated. Concomitant medication, therapeutics 
interventions, or underlying conditions do not provide a sufficient 
explanation for the observed AE 
7.10.5 
Unexpected adverse events 
Any AE assessed at least as possibly related to the IP will be assessed for expectedness by the 
sponsor or designee. An AE is considered “unexpected” if its nature or severity is not consistent 
with information in the MC2-01 Investigator’s Brochure(23) (for MC2-01 cream) or Daivobet® / 
Dovobet®Gel Summary of Product Characteristics (SmPC)(24) (for active comparator). 
 “Unexpected” as used in this definition, also refers to AEs that are mentioned in the Investigator’s 
Brochure or SmPC 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. 
7.10.6 
Trial medication overdose 
An overdose of the IP, i.e., a dose that is higher than the highest dose under clinical investigation 
or the known therapeutic dose, will be fully documented even if no toxic effects were observed 
and will be considered an AE. 
The application should only be done once daily, and the treated area should not be >30% of the 
body surface area.  
 
Use of MC2-01 cream in excessive amounts may cause elevated serum calcium, which should 
rapidly subside when treatment is discontinued. Excessive prolonged use of topical corticosteroids 
may suppress the pituitary-adrenal functions, resulting in secondary adrenal insufficiency that is 
usually reversible. In such cases, symptomatic treatment is indicated. 
7.10.7 
Pregnancy 
Any pregnancy occurring from date of the Informed Consent signature until trial completion must 
be reported immediately to MC2 or designee as soon as it becomes known to the investigator and 
not later than within 24 hours of his/her knowledge of the occurrence of the pregnancy (see Section 
7.10.9).  
All pregnancies should be actively followed through to resolution (i.e., delivery, miscarriage, or 
abortion). The corresponding report(s) should be submitted within the same timelines as mentioned 
above. A pregnancy per se is not considered an SAE.  
7.10.8 
Serious adverse event 
An SAE is any untoward medical occurrence that at any dose: 


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• Results in death 
• Is life-threatening 
• Requires in-patient hospitalisation or prolongation of existing hospitalisation 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect, or is an important medical event 
• Other serious or important medical event  
The death of a subject enrolled in a trial is per se not an event, but an outcome. Any event resulting 
in a fatal outcome must be fully documented and reported, regardless of the causality relationship 
to the IP. 
Any medical important events that may not result in death, be life-threatening, or require 
hospitalisation may be considered an SAE when, based on appropriate medical judgment, they 
may jeopardise the subject or the subject may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definitions.  
Any pre-planned hospitalisations that are known at the time of signing the informed consent form 
(ICF) will not be recorded as SAEs, however they will be recorded as AEs only.  
Any SAE, whether or not deemed drug-related or expected, must be reported immediately to the 
MC2 or designee as soon as it becomes known to the investigator and not later than within 24 hours 
of his/her knowledge of the occurrence of an SAE (see Section 7.10.9). The investigator will 
document such events in the best possible detail on the SAE Report Form.  
If the investigator becomes aware of an SAE after the end of the clinical trial that is possibly related 
to the IP, he/she must inform the sponsor immediately. 
A SUSAR is an SAE that is both unexpected (not consistent with the current Investigator’s 
Brochure(23) or Daivobet® / Dovobet® Gel SmPC(24)  (for active comparator), and for which 
there is evidence to suggest a causal relationship between the drug and the SAE. The Institutional 
Review Board (IRB)/Independent Ethics Committee (IEC) will be informed of SUSARS 
according to local requirements. All investigators participating in the trial will also be notified of 
unexpected SAEs. The sponsor will report SAEs and other events requiring expedited reporting 
to regulatory authorities as required.  
Investigator instructions for reporting SAEs are provided in Section 7.10.9. 


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7.10.9 
Reporting of Serious Adverse Events and Pregnancies 
7.10.9.1 
Contact person(s) and number(s) 
SAEs and pregnancies must be reported immediately (i.e., not later than 24 hours after first 
knowledge). The SAE or pregnancy report should be e-mailed or faxed to United BioSource 
Corporation (UBC) using the following e-mail or fax-number:  
Email: EUSafety@ubc.com 
Fax number:  +41 225 964 446 
 
 
7.10.9.2 
Reporting procedures 
Serious adverse events 
For each SAE, the investigator will complete a Serious Adverse Event Report Form and assess the 
relationship of each SAE to trial treatment. The completed form(s) should be sent immediately 
(and not later than within 24 hours of first knowledge of the SAE) electronically to the UBC using 
the SAE Reporting by email or fax.  
Follow-up reports regarding the status of the SAE and the subject’s subsequent course should be 
submitted until the SAE has subsided, the condition stabilised (in the case of persistent 
impairment), the subject receives alternative therapy, or the subject dies. The form and fax 
confirmation will be retained. Contacts for reporting SAEs, pregnancies and other safety concerns 
are provided to each site.  
7.11 
Unscheduled Visit 
An unscheduled visit may be performed at any time during the trial if judged necessary by the 
investigator, such as for a severe reaction, suspected pregnancy, clinically significant AE, or 
clinically significant local skin reaction result. Details of the event are to be recorded in the 
subject’s records. 
7.12 
Follow-up Visit 
An on-site follow-up visit is required for the following reasons:  
• 
Unresolved treatment-related AEs. 
• 
If the albumin-corrected serum calcium was above the normal reference range at the Week 8 
visit a repeat test should be done 14 days (± 2 days) after.  
A telephone call will be made 2 weeks after the Week 8 visit as follow-up for all subjects without 
unresolved treatment-related AEs or abnormal, elevated albumin-corrected serum calcium to ask 
for the wellbeing of the subject. 


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7.13 
Early Termination 
The subjects are free to withdraw at any time if they choose without providing reasons. All efforts will 
be made, however, to encourage the subject to continue in the trial or at least come for the Week 
8 visit. This also is applicable in case administration of the IP has been terminated.  
If the subject is considered non-compliant with protocol procedures, for example started 
prohibited medication, all efforts will be made to encourage the subject to continue on treatment 
(if no safety concerns) or at least come for the Week 8 visit. 
 
The following procedures should be performed at the early termination visit:  
• 
Collect all trial materials from the subject. 
• 
Assess compliance 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Record any AEs. 
• 
Physical examination and vital signs   
• 
Perform a urine pregnancy test for females of childbearing potential. 
• 
Biochemistry and urinalysis.  
• 
PGA 
• 
mPASI 
• 
BSA 
• 
SGA 
• 
DLQI 
• 
EQ-5D 
• 
Psoriasis Treatment Convenience Scale 
• 
Local Skin Reactions  
 
 


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8.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
STATISTICAL AND ANALYTICAL PLANS 
8.1 
General Considerations for Data Analysis 
The methodology presented below represents a brief overview of the statistical methods that will 
be fully detailed in the statistical analysis plan (SAP). The SAP will be finalised before the 
database is locked. Any changes to the methods described in the final SAP will be described and 
justified in the clinical trial report. All statistical analyses will be performed using SAS® statistical 
software (Version 9.2 or higher). Statistical significance will be tested at the 2-sided 5% level 
unless otherwise specified.   
Subjects will be randomised in a 3:1:3 ratio (MC2-01 cream: MC2-01 cream vehicle: active 
comparator), stratifying by trial site. The aim is to randomise 14 subjects or more at each site. 
Furthermore, on a country level, it will be ensured that up to 30 % of the population can be subjects 
with mild disease (based on the PGA performed at Baseline), as monitored by data management. 
It is planned that the data from trial sites that participate in this trial will be combined so that an 
adequate number of subjects will be available for analysis. Trial sites yielding fewer than 14 
subjects overall will be combined in order of geographical proximity. The exact composition of 
these “analysis sites” will be determined and documented prior to breaking the trial blind. In 
statistical models, site will refer to trial site or analysis site, if combination of trial sites is needed.    
8.2 
Sample Size and Power Considerations 
The primary endpoint is percentage change from baseline in mPASI at Week 8. The primary 
endpoint will be used for superiority evaluations of MC2-01 cream and active comparator versus 
vehicle, and the non-inferiority evaluation of MC2-01 cream versus active comparator. The 
primary endpoint has been chosen as percentage change from baseline instead of absolute change, 
as this was the endpoint in the studies used to determine the non-inferiority margin.  
The sample size calculation is based on the non-inferiority margin for the treatment difference in 
percentage change from baseline in mPASI at Week 8.     
Non-inferiority margin:  
According to information from experienced dermatologists as well as data from an observational 
study (28, 29), the two marketed products, Daivobet® Gel and Daivobet® Ointment, appear to be 
equally effective. The summary of mean reductions in mPASI in randomized trials with Daivobet® 
Gel and Daivobet® Ointment is shown below (Table 8-1 and Table 8-2).  
 
 


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Table 8-1 Published mean reduction of PASI for active treatment from baseline to 8-weeks 
reported in CAL/BDP Gel phase 2/3 trials 
Reference 
Patients 
N 
mPASI Baseline 
(mean) 
PASI mean reduction from 
Baseline to Week 8 (%) 
SD 
Menter 2013 (30) 
482 
7.9 
-55.8 
34.4 
Langley 2011(31) 
183 
9.39 
-57.0 
29.6 
Fleming 2010 (12) 
162 
7.7 
-55.3 
33.3 
Table 8-2 Published mean reduction of PASI for active treatment from baseline to 8-weeks 
reported in CAL/BDP Ointment phase 3 trials 
Reference 
Patients 
N 
mPASI Baseline (mean) 
PASI mean reduction from 
Baseline to Week 8 (%) 
95% CI 
95% 
CI 
Guenther 2002 (32) 
150 
9.9 
-68.6 
-64.8 
-72.4 
Kaufmann 2002 (13) 
490 
9.9 
-71.3 
-69.1 
-73.6 
Kragballe 2004; (33)  
Kragballe 2006 (34)  
645 
10.4 
-68.7 
-66.9 
-70.5 
Ortonne 2004 (35) 
249 
9.7 
-65.0 
-61.4 
-68.6 
CI: Confidence interval 
Based on these trials, a random-effects meta-analysis of mean reduction in mPASI at end of trials 
shows an estimated difference of 12.71 percentage points [95% CI 8.00 to 17.41] between 
Daivobet® Gel and Daivobet® Ointment, suggesting that –12 percentage points is a clinically 
acceptable margin for non-inferiority. Therefore, the non-inferiority limit is set to –12 percentage 
points. 
Assumptions for sample size calculation:  
• The common standard deviation is assumed to be 38 (based on the assumption of an SD of 35 
in the active treatment arms (see above Daivobet® Gel studies), 50 in the vehicle arm (found 
to be the largest SD in the above Daivobet® Gel studies), and the 3:1:3 ratio) 
• The error probability is set to 0.05 for a 2-sided test 
Under these assumptions, a sample size of N=204 per active treatment group for the non-inferiority 
evaluation, assuming 0 difference, results in a power of 88.9%. Thus, a total of 476 subjects should 
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With 476 subjects randomised 3:1:3, and the assumption that the effect of both active treatments 
is -56 percentage points (the average effect found in the gel studies), and the effect of MC2-01 
cream vehicle is -27 percentage points (the largest effect found for the ointment, found in the 
MCB-9905 INT study), the power for each of the superiority comparisons of MC2-01 cream and 
active comparator to MC2-01 cream vehicle with respect to mPASI is more than 99%. If 30% of 
subjects treated with either MC2-01 cream or active comparator respectively 11% of subjects 
treated with MC2-01 cream vehicle will have PGA success, the power for the each of the 
superiority comparisons with respect to PGA success is 90.4%.    
8.3 
 Analysis Populations 
The analysis populations are defined as follows:  
• Intent To Treat (ITT) population: all randomised subjects  
• Per Protocol (PP) population: all subjects in the ITT population who complete the trial 
without any major protocol violations. The PP population will be determined and documented 
in blind review of the database conducted prior to un-blinding the trial database. Subjects may 
be excluded from the PP population if any of the following criteria are met: 
o Failure to meet key Inclusion/Exclusion criteria; i.e. violation of inclusion/exclusion 
criteria that according to medical judgement may impact the primary endpoint 
analysis  
o Usage of restricted medications/treatments; i.e. medications/treatments that according 
to medical judgement may impact the primary endpoint analysis 
o Nonadherence to the visit schedule at Week 8: -7/+10 days 
o Noncompliance with the trial treatment regimen; adherence to the treatment schedule 
defined as application of IP as specified by the investigator for at least 80% of the 
days from Day 1 to Week 8 visit, and at least 80% of the days from Week 4 visit to 
Week 8 visit 
• Safety population: all randomised subjects who are dispensed the trial medication, excluding 
subjects who return all the trial medication unused.  
Subjects in the ITT and PP populations will be analyzed as randomized, and subjects in the Safety 
population will be analysed as treated.   
The ITT population will be used for the analyses of efficacy and other endpoints, while the Safety 
population will be used for all safety analyses. The PP population will be used in sensitivity 
analyses for the non-inferiority evaluations, and in a sensitivity analysis for the PCTS score 
evaluation.   


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8.4 
Estimands 
The efficacy endpoints will be analyzed focusing on two different estimands:  
Primary estimand (treatment-policy): the effect of initiating the treatment regimen in subjects with 
mild-to-moderate psoriasis, with or without any other psoriasis treatment, and whether or not the 
subject adhered to the treatment regimen.   
Thus, for the treatment-policy estimand all available data will be used.   
Secondary estimand (hypothetical-strategy): the expected effect in subjects with mild-to-moderate 
psoriasis if all subjects adhered to the treatment regimen and did not take any other psoriasis 
treatment (=treatment that according to medical judgement may improve psoriasis).  
This is interpreted in the sense that subjects did not initiate other treatment that according to 
medical judgement may improve psoriasis, and for visits after baseline adhered to the treatment 
schedule defined as application of IP as specified by the investigator at the previous site visit for 
at least 70% of the days from baseline visit to Week 4, Week 4 to Week 6 and Week 6 to Week 8. 
For example, applying IP for 10 out of 14 days is considered adherence, while 9 out of 14 days is 
not. Thus, for the hypothetical-strategy estimand, only data at or prior to use of other treatment 
that may improve psoriasis according to medical judgement, and prior to non-adherence to 
treatment schedule is used. Missing data, data after use of other psoriasis treatment, and data after 
non-adherence is imputed. 
8.5 
Handling of Missing Data 
For analyses using the PP population, no imputations will be made for missing data.  
For analyses using the ITT population, both multiple imputation (MI), last-observation-carried 
forward (LOCF), and non-responder imputation (NRI) will be used. MI will be the primary 
imputation method and is described below, and sensitivity analyses utilizing LOCF and NRI will 
be performed to assess the robustness of the imputation assumptions of MI.  
Multiple imputation (for continuous endpoints):  
Post-baseline missing efficacy data will be multiple imputed separately for each treatment group 
using a Markov Chain Monte Carlo (MCMC) method to obtain a monotone missing data pattern, 
after which imputation is done using a monotone regression method. In more detail the process is 
as follows:  
Impute to get a monotone missing data pattern: Intermittent missing values are imputed using 
MCMC separately for each treatment group to obtain 100 copies of the original dataset with a 
monotone missing data pattern. 


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Impute Week 1 data: For each of the 100 datasets and each treatment group separately, an 
analysis of covariance (ANCOVA) model is fitted to the endpoint measured at Week 1. The 
ANCOVA model will include the effects of site and baseline PGA as factors and baseline value 
of the endpoint as a covariate. For each treatment group and each dataset, the estimated 
parameters and their variances are used to impute the endpoint at Week 1 for the missing values. 
Repeat stepwise imputation: For each of the 100 datasets and each treatment group separately, 
missing values at Week 4 are imputed in the same way as for Week 1 using a similar ANCOVA 
model but including also the (possibly imputed) endpoint at Week 1 as an additional covariate. 
For each dataset and each treatment group, the estimated parameters and their variances are used 
to impute the missing values at Week 4 in the dataset. This stepwise procedure is repeated 
sequentially for Week 6 and Week 8, including in the ANCOVA models the additional covariate 
(possibly imputed) endpoint at Week 4, and, for the imputation for Week 8, also the covariate 
(possibly imputed) endpoint at Week 6. 
Data analysis using MI, continuous endpoint:  
Use MI. For each of the 100 complete, imputed datasets, the endpoint at Week 8 will be analysed 
using an ANCOVA model with effects of treatment, site, and baseline PGA as factors and the 
baseline value of the endpoint as a covariate. The estimated differences between the treatments at 
Week 8 will be derived together with the associated standard error. The estimates and standard 
errors from the 100 analyses are pooled to one estimate and associated standard error using 
Rubin’s rule to draw inference. From these pooled results, the 95% CI for the treatment 
differences is calculated. 
Data analysis using MI, for dichotomous endpoint:  
Use MI for the underlying quantitative variable, prior to dichotomizing the endpoint. For each of 
the 100 complete, imputed datasets, dichotomize the endpoint at Week 8. Then analyze using a 
logistic model with effects of treatment, site, baseline PGA as factors, and if applicable the baseline 
value of the endpoint as a covariate. The estimated log odds ratios between the treatments at Week 
8 will be derived together with the associated standard error. The estimates and standard errors 
from the 100 analyses are pooled to one estimate and associated standard error using Rubin’s rule 
to draw inference. From these pooled results, the 95% CI for the odds ratios between treatments 
are calculated. 
8.6 
Analyses of Efficacy 
All efficacy endpoints will be described using summary statistics for each treatment group by visit.  
For mPASI absolute values, absolute reduction, and percentage reduction from baseline will be 
summarized using mean, median, SD, quartiles and ranges. Frequency counts and percentages for 


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PGA, SGA, and PGA for scalp, will be provided. For PGA success and mPASI 75, frequency 
counts and percentages will be provided.  
The efficacy endpoints will primarily be analyzed using the treatment-regimen policy estimand for 
the ITT population and imputing missing data using MI.  
8.6.1 
Primary Efficacy Endpoint  
The primary efficacy endpoint is the percentage change in mPASI on the body (trunk and/or limbs) 
from baseline to Week 8.  
8.6.1.1 
Analysis of primary endpoint  
Superiority analysis 
First the percentage change in mPASI from baseline to Week 8 for MC2-01 cream and the active 
comparator will be compared with that of MC2-01 cream vehicle for a superiority evaluation 
using the treatment-policy estimand for the ITT population and imputing missing data using MI.  
The comparison will be done using an ANCOVA model including treatment, site, and baseline 
PGA as factors, and baseline mPASI as covariate. The estimated differences between MC2-01 
cream and MC2-01 cream vehicle, and between active comparator and MC2-01 cream vehicle, 
will be reported together with the associated standard error, the 95% confidence interval, and a 
test corresponding to no difference between treatments. 
Non-inferiority analysis  
Next, if and only if superiority to MC2-01 cream vehicle can be claimed for both MC2-01 cream 
and active comparator on the 5% significance level, MC2-01 cream will be compared to active 
comparator for a non-inferiority evaluation using the treatment-regimen estimand for the ITT 
population and imputing missing data using MI.   
Percentage change in mPASI from baseline to Week 8 will be compared between MC2-01 cream 
and active comparator for a non-inferiority evaluation using the -12 percentage points non-
inferiority margin. The comparison will be done using the same model as applied for the analysis 
of superiority vs. vehicle as described above: an ANCOVA model including treatment, site, and 
baseline PGA as factors, and baseline mPASI as covariate. The estimated difference between 
MC2-01 cream and active comparator will be reported together with the associated standard 
error, and the 95% confidence interval. If the lower limit of the 95% confidence interval is above 
-12 percentage points, non-inferiority is demonstrated.   


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8.6.1.2 
Sensitivity analyses 
For the superiority analyses of MC2-01 cream and active comparator to MC2-01 cream vehicle, 
as well as for the non-inferiority analysis of MC2-01 cream to active comparator, the below 
sensitivity analyses will be performed.  
Internal validity   
The primary analysis using MI assumes that data are missing at random within each treatment arm. 
For each hypothesis, the sensitivity of this assumption is investigated using a so-called tipping 
point analysis; a penalty (a number) is added to all imputed Week 8 values in the MC2-01 treatment 
group or (when testing superiority of active comparator vs. vehicle) in the active comparator group, 
and the analysis is repeated on the ITT population for the treatment-regimen estimand. The penalty 
d is gradually increased until the point, the tipping point, where the conclusion (superiority or non-
inferiority depending on the analysis) no longer is demonstrated. If the tipping point is considered 
a clinical plausible difference, the tipping-point analysis does not support the primary analysis.  
External validity   
• The primary analysis is repeated using the hypothetical-strategy estimand based on the ITT 
population and imputing missing data using MI.  
• The primary analysis using the treatment-policy estimand and imputing missing data using MI 
is repeated based on the PP population.  
8.6.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
• PGA success on the body (trunk and/or limbs) at Week 8 
• Subject assessment of treatment convenience at Week 8 using the PTCS Analysis of secondary 
endpoints 
To control the global Type-I error, the secondary endpoints will be tested in hierarchical order, if 
and only if non-inferiority can be demonstrated for the primary endpoint. The endpoints will be 
analyzed using the treatment-regimen policy estimand for the ITT population. 
For PGA success, missing PGA values will be imputed using MI considering PGA as a continuous 
endpoint. 
• PGA success: PGA success of both MC2-01 cream and active comparator will be compared 
with that of MC2-01 vehicle for a superiority evaluation. The comparison will be done using 
a logistic model with treatment, baseline PGA, and site as factors.  


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• PGA success: Non-inferiority of MC2-01 cream versus active comparator. PGA success will 
be compared between MC2-01 cream and active comparator for a non-inferiority evaluation 
using a -10 percentage points non-inferiority margin, as -10 percentage point is considered the 
largest clinically acceptable loss of effect. This non-inferiority margin was also used in the 
MC2-01-C2 trial (1). The percentage of subjects in each group with treatment success will be 
calculated along with its 95% confidence interval (CI) using normal approximation. A 95%, 
2-sided CI for PM-PA, where PM and PA are the PGA treatment success rate at Week 8 for 
MC2-01 cream and active comparator respectively, will be computed using normal 
approximation using Proc FREQ with RISKDIFF option. MC2-01 will be considered non-
inferior to active comparator if the lower bound of the 2-sided 95% CI is ≥ -10% points. 
• PCTS: Superiority of MC2-01 cream versus active comparator. A PCTS score is considered 
invalid, if subject has discontinued study medication more than 7 days prior to the day of 
assessment. Missing and invalid PTCS scores will be imputed using the last valid measure 
prior to the visit (LOCF). This approach corresponds to a “PCTS while on treatment” estimand. 
The PCTS score will be compared between MC2-01 cream and active comparator using an 
ANCOVA model with treatment, baseline PGA, and site as factors.  
• mPASI: In analogy with the analysis of the primary endpoint, superiority of MC2-01 cream 
versus active comparator will be evaluated using an ANCOVA model including treatment, site, 
and baseline PGA as factors, and baseline mPASI as covariate. Missing mPASI values will be 
imputed using MI. 
• PGA: Superiority of MC2-01 cream versus active comparator. PGA success will be compared 
between MC2-01 cream and active comparator using a logistic model with treatment, baseline 
PGA, and site as factors.  
8.6.2.1 
Sensitivity analyses 
• For PGA success, a sensitivity analysis will be performed where missing values are imputed 
as non-responders (NRI). Another sensitivity analysis will be performed repeating the primary 
analysis for the hypothetical-strategy estimand based on the ITT population and imputing 
missing data using MI.  
• For PCTS the analysis will repeated for the PP population instead of the ITT population with 
the same imputation (LOCF).  
• For mPASI the same sensitivity analyses as for the primary endpoint will be performed.  
8.6.3 
Other Endpoints 
Efficacy 
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• mPASI 75 (at least 75% reduction in mPASI from baseline) on the body (trunk and/or limbs) 
at Week 4 and Week 8; 
• Change from baseline in SGA at Week 4 and Week 8; 
• Change from baseline in PGA for the scalp at Week 4 and Week 8;  
Patient reported outcome  
• Subject assessment of treatment convenience at Week 4 using the PTCS;  
• Change from baseline in DLQI score at Week 4 and Week 8; 
• Change from baseline in EQ-5D score at Week 4 and Week 8; 
8.6.3.1 
Analysis of other endpoints 
The statistical analyses of other endpoints will be exploratory only, and no formal statistical testing 
will be conducted.  
Efficacy 
The efficacy endpoints will be analyzed using the treatment-regimen policy estimand for the ITT 
population and imputing missing data using MI. For the dichotomous endpoints based on mPASI, 
values of mPASI will be imputed, and then dichotomized.  
• Percentage change from baseline in mPASI at Week 4 will be analyzed like the primary 
endpoint including the same sensitivity analyses    
• mPASI 75 at Week 4 and Week 8, and PGA success at Week 4 will be analyzed like PGA 
success at Week 8 (secondary endpoint), with the analyses of mPASI 75 including mPASI at 
baseline as a covariate.  
• Change from baseline in SGA at Week 4 and Week 8, and change from baseline in PGA for 
the scalp at Week 4 and Week 8 will be presented descriptively only  
Patient reported outcome  
• The PCTS score at Week 4 will be analyzed like the PCTS score at Week 8 
• The DLQI score as well as the scores for the individual domains (symptoms and feelings, 
daily activities, leisure, work and school, and personal relationship) will be summarized by 
trial visit and treatment group. Missing values, if any, will be incorporated based on the 
developers scoring instructions. Missing domains will be imputed using MI and then 
combined to a total score. Change from baseline in DLQI score at Week 4 and Week 8 will be 
analyzed for the treatment-regimen estimand and the ITT population using an ANCOVA 
model with treatment, site, baseline PGA, and baseline DLQI as factors  


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• For the EQ-5D VAS score as well as the 5 dimensions mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression, will be summarized by trial visit and treatment 
group. Change from baseline in EQ-VAS score at Week 4 and Week 8 will be analyzed for 
the treatment-regimen estimand and the ITT population imputing missing data using MI and 
using an ANCOVA model with treatment, site, baseline PGA, and baseline EQ-VAS as 
factors   
8.7 
Analysis of Safety 
The assessment of safety will be based mainly on the frequency of AEs, on the number of 
laboratory values that fall outside of predetermined ranges, and on local skin reactions.  
8.7.1 
Adverse events  
AEs will be summarised by the Medical Dictionary for Regulatory Activities (MedDRA) system 
organ class and preferred term. The incidence of AEs (percent of subjects reporting the AE at least 
once) as well as the number of AEs will be tabulated separately for each treatment group by 
severity and relationship to drug.  
8.7.2 
Local Skin Reaction Assessment 
Assessments of local skin reaction will be performed at all post-screening visits for all subjects in 
the trial.  These local skin reaction assessments (LSRs) will be made by the investigator.  The 
treatment area and the immediate surrounding area will be assessed.  
The LSR sum score will be summarized by trial visit and treatment group. The LSR intensities, 
scored as 0=none, 1=mild, 2=moderate, or 3=severe, will be summarized by trial visit and 
treatment group for each of the LSR categories.  
In addition, for each LSR category, the most intense reaction over the course of the trial will be 
determined for each subject, and the frequency distributions of these scores will be tabulated. 
8.7.3 
Other safety variables 
Clinical laboratory values will be reported as complete listings of individual subject data. 
Laboratory parameters will include:  
• Serum biochemistry: serum calcium (albumin corrected), serum albumin, serum alkaline 
phosphatase, serum phosphate, plasma parathyroid hormone.  25-OH Vitamin D (Assessed at Visit 
1 and used to stratify patients and treatment effect on calcium metabolism).  
• Urinalysis: urinary calcium, urinary phosphate, urinary calcium:creatinine ratio.  
Clinical laboratory data will be summarised by presenting shift tables using extended normal 
ranges (baseline to most extreme post-baseline value), by presenting summary statistics of raw 


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data and change from baseline values (means, medians, standard deviations, ranges), and by the 
flagging of notable values in data listings.  
Data from other tests (e.g., vital signs) will be considered as appropriate and listed. Notable values 
will be flagged, and any other information collected will be listed as appropriate. Any statistical 
tests performed to explore the data will be used only to highlight any interesting comparisons that 
may warrant further consideration. 
9.0 
CHANGES IN THE PLANNED TRIAL 
9.1 
Protocol Amendments 
Except for administrative changes, any changes or additions to this clinical trial protocol require a 
written protocol amendment that must be approved by the IRB before implementation.  
These requirements for approval should in no way prevent any immediate action from being taken 
by the investigator or MC2 in the interests of preserving the safety of all subjects included in the 
trial. If an immediate change to the protocol is felt to be necessary by the investigator and is 
implemented for safety reasons, MC2 or designee should be notified and the IRB should be 
informed according to their reporting requirements. 
9.2 
Termination or Suspension of the Trial 
MC2, the investigator, the IRB/IECs or competent authorities serves the right to terminate or 
suspend the trial, part of the trial or a trial site at any time, but agreement on procedures to be 
followed must be obtained. In case of premature termination or suspension of the trial, the contract 
research organization (CRO) project manager will promptly inform the investigators, regulatory 
authorities, and IRBs about the premature termination or suspension, including the reason for it. 
In terminating the trial, MC2 and the investigator will ensure that adequate consideration is given 
to the protection of the subjects’ interests. The trial must be terminated if the perception of the 
benefit/risk ratio (judged from clinical signs and symptoms, (S)AEs and/or remarkable safety 
laboratory changes) becomes unfavorable for the continuation of the trial.  
10.0 
DATA HANDLING AND RECORD KEEPING 
10.1 
Recording of Data 
10.1.1 
Source documents 
Source data are all the information in original records and copies of original records of clinical 
findings, observations, or other activities in the trial, which are necessary for the reconstruction 
and evaluation of the trial.  
Trial data collection procedures must ensure that each data element can be traced with a high level 
of confidence from its originator or recorder to its representation in the trial database and then to 
its place in the analysis and report of trial results. Once recorded, the trial data must be protected 


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from unauthorised modification or deletion, and all authorised modifications and deletions must 
be securely linked in the permanent record with their author, time of change, and reason for change 
(i.e., the audit trail must be maintained). 
The investigator will permit trial-related monitoring, audit(s), IRB/IEC review(s) and regulatory 
inspection(s), with direct access to all the required source records. 
The principal investigator will certify the data to be accurate and complete and will release the 
data for transmittal to MC2 or designee. 
Source records need to be preserved for the maximum period of time permitted by local 
requirements (see Section 10.2). For each subject enrolled, the investigator will indicate in the 
source record(s) that the subject participated in the trial. 
10.1.2 
Case report forms 
The primary data collection tool for the trial is an eCRF designed specifically for the trial. For each 
subject enrolled in the trial, an eCRF will be completed by the trial coordinator and signed by the 
investigator or his/her designate.  
The investigator will be responsible for ensuring the accuracy of all data entered in the eCRFs. All 
eCRFs are to be completed in a timely manner. 
Errors occurring in the eCRFs will be queried. Queries raised by data reviewers must be addressed 
by site personnel. 
On request, the investigator will provide the MC2 with additional data relating to the trial, or copies 
of relevant source records, duly anonymised (i.e., subject’s name is redacted). 
10.2 
Retention of Documents 
The investigator shall take responsibility for maintaining adequate and accurate source documents 
of all observations and data generated during this trial, including any data clarification forms 
received from the MC2 or designee. Such documentation is subject to inspection by the sponsor 
or its agents, the US Food and Drug Administration (FDA) and/or other regulatory agencies. The 
investigator is responsible for retention of essential documents including the Investigator Trial File 
until MC2 informs the investigator that the documents are no longer to be retained or longer if 
required by local regulations.  
11.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 
Direct Access to Source Documents 
As specified in the investigator’s agreement, the investigator agrees to allow trial-related 
monitoring, audit(s), IRB/IEC review(s) and regulatory inspection(s), with direct access to all the 


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required source records, and to allocate his/her time and the time of his/her staff to the 
auditor/inspector to discuss findings and any issues.  
11.2 
Monitoring Procedures 
The Clinical Trial Monitor will contact and/or visit the investigator site periodically to verify the 
adherence to the protocol, the maintenance of trial-related source records, and the completeness 
and accuracy of all eCRF entries compared to source data. The investigator will cooperate with 
the trial monitor to ensure that any discrepancies that may be identified are resolved. 
11.3 
Audit and Inspection 
The investigator will make all the trial-related source data and records available to a quality 
assurance auditor mandated by the sponsor, or to domestic or foreign regulatory inspectors, after 
reasonable notice. The main purposes of an audit or inspection are to confirm that the rights and 
well-being of the subjects have been adequately protected, and that all data relevant for the 
evaluation of the IP have been processed and reported in compliance with GCP/ICH and applicable 
regulatory requirements. 
The investigator is to notify the MC2 or designee immediately of any inspection by regulatory 
authorities or IRBs. 
12.0 
ETHICS 
12.1 
Ethical Conduct of the Trial 
This trial must be carried out in compliance with the protocol and the applicable laws and 
regulatory requirements of the appropriate regulatory agency. The trial must be conducted in 
accordance with the ethical principles originating from the Declaration of Helsinki and 
amendments and the ICH-GCP guidelines. 
12.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
This protocol, the proposed informed consent form, and other information for subjects must be 
reviewed and approved by an IRB or IEC, before the start of the trial, in compliance with local 
regulations. This committee must also approve any amendments to the protocol, other than 
administrative ones, before initiation of the amendment procedures. 
12.3 
Subject Information and Consent 
Before participation in the trial, each subject is required to provide written consent to participate 
in the trial. No trial-specific procedures will be performed before a subject’s informed consent is 
obtained.  


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12.4 
Disclosure and Confidentiality 
12.4.1 
Confidentiality of trial documentation 
By signing the protocol, the investigator agrees to keep all information provided by the sponsor in 
strict confidence and to request similar confidentiality from his/her staff and the IRB or IEC. Trial  
documents provided by the trial sponsor (i.e., protocols, Investigators' Brochures, eCRFs and other 
material) will be stored appropriately to ensure their confidentiality. The information provided by 
the sponsor to the investigator may not be disclosed to others without direct written authorisation 
from the sponsor, except to the extent necessary to obtain informed consent from subjects who 
wish to participate in the trial. 
12.4.2 
Privacy of individual health information  
The investigator will undertake to protect the privacy of all individually identifiable health 
information except as specifically authorised by each individual subject through the written 
informed consent. The Informed Consent document will include a request of the subject’s consent 
to release the collected data for research purposes in such a way that the individual’s identity 
remains masked. While all data records will be identified by the corresponding subject number, 
the identity of the subject will be held in confidential source documents at the trial site. All trial 
personnel with access to this information are legally bound not to disclose such information. 
13.0 
EMERGENCY PROCEDURES 
13.1 
Emergency Unblinding  
Un-blinding by trial personnel should be performed only in emergencies where knowledge of the 
subject’s treatment assignment is essential for further management of the subject’s medical care. 
Un-blinding a subject’s treatment assignment under any other circumstances will be considered a 
protocol violation.  
The investigator should assess the relationship of any AEs to administration of the IP prior to un-
blinding. 
The investigator is strongly encouraged to contact the trial Medical Expert before un-blinding any 
subject’s treatment assignment but must do so within 1 working day after the un-blinding. The 
subject’s treatment code should not be communicated to the Medical Expert. The un-blinding will 
be documented by the investigator.  
If the blind is broken for any reason, the investigator must record the date and reason for breaking 
the blind on the appropriate trial documents. 
14.0 
INSURANCE 
MC2 has taken out appropriate insurance policies covering the subjects in the clinical trial in 
accordance with applicable laws and regulations. 


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15.0 
PUBLICATION POLICY 
The clinical trial information will be posted on www.clinical trial.gov and in accordance with 
applicable regulations.  
All publications (e.g., manuscripts, abstracts, oral/slide presentations, book chapters) based on this 
trial must be submitted to MC2 for review, as specified in the Clinical Trial Agreement between 
the institution, investigator and MC2 or its designee. 
 
 


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16.0 
REFERENCES 
1. 
MC2Therapeutics. A Randomised, Multicentre, Investigator-Blind, Parallel-Group Trial 
to Evaluate the Efficacy and Safety of MC2-01 Cream Compared to MC2-01 Cream 
Vehicle and Active Comparator in Subjects with Mild-to-Moderate Psoriasis Vulgaris. 
2017. 
2. 
Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed 
psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol. 
2009;60(2):218-24. 
3. 
Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis 
and psoriatic arthritis. J Autoimmun. 2010;34(3):J314-J21. 
4. 
Schafer T. Epidemiology of psoriasis. Review and the German perspective. Dermatology. 
2006;212(4):327-37. 
5. 
Nestle FO, Kaplan DH, Barker J. Mechanisms of Disease: Psoriasis. N Engl J Med. 
2009;361(5):496-509. 
6. 
Griffiths CE, Barker J. Pathogenesis and clinical features of psoriasis. Lancet. 
2007;370(9583):263-71. 
7. 
Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl M. Association of patient-
reported psoriasis severity with income and employment. J Am Acad Dermatol. 
2007;57(6):963-71. 
8. 
Dubertret L, Mrowietz U, Ranki A, van de Kerkhof PC, Chimenti S, Lotti T, et al. 
European patient perspectives on the impact of psoriasis: the EUROPSO patient 
membership survey. Br J Dermatol. 2006;155(4):729-36. 
9. 
Rapp SR, Feldman S, Exum ML, Fleischer AB, Jr., Reboussin DM. Psoriasis causes as 
much disability as other major medical diseases. J Am Acad Dermatol. 1999;41(3 Pt 
1):401-7. 
10. 
Boehncke WH, Boehncke S, Tobin AM, Kirby B. The 'psoriatic march': a concept of how 
severe psoriasis may drive cardiovascular comorbidity. Exp Dermatol. 2011;20(4):303-7. 
11. 
Zanni GR. Psoriasis: issues far more serious than cosmetic. Consult Pharm. 
2012;27(2):86-. 
12. 
Fleming C, Ganslandt C, Guenther L, Johannesson A, Buckley C, Simon JC, et al. 
Calcipotriol plus betamethasone dipropionate gel compared with its active components in 
the same vehicle and the vehicle alone in the treatment of psoriasis vulgaris: a 


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randomised, parallel group, double-blind, exploratory study. Eur J Dermatol. 
2010;20(4):465-71. 
13. 
Kaufmann R, Bibby AJ, Bissonnette R, Cambazard F, Chu AC, Decroix J, et al. A new 
calcipotriol/betamethasone dipropionate formulation (Daivobet) is an effective once-daily 
treatment for psoriasis vulgaris. Dermatology. 2002;205(4):389-93. 
14. 
Lebwohl M, Tyring S, Bukhalo M, Alonso-Llamazares J, Olesen M, Lowson D, et al. 
Fixed Combination Aerosol Foam Calcipotriene 0.005% (Cal) Plus Betamethasone 
Dipropionate 0.064% (BD) is More Efficacious than Cal or BD Aerosol Foam Alone for 
Psoriasis Vulgaris: A Randomized, Double-blind, Multicenter, Three-arm, Phase 2 Study. 
J Clin Aesthet Dermatol. 2016;9(2):34-41. 
15. 
Lovato P, Norsgaard H, Tokura Y, Ropke M. Calcipotriol and betamethasone 
dipropionate exert additive inhibitory effects on the cytokine expression of inflammatory 
dendritic cell-Th17 cell axis in psoriasis. J Dermatol Sci. 2016;81(3):153-64. 
16. 
Gniadecki R, Gniadecka M, Serup J. Inhibition of glucocorticoid-induced epidermal and 
dermal atrophy with KH 1060--a potent 20-epi analogue of 1,25-dihydroxyvitamin D3. 
Br J Pharmacol. 1994;113(2):439-44. 
17. 
Norsgaard H, Kurdykowski S, Descargues P, Gonzalez T, Marstrand T, Dunstl G, et al. 
Calcipotriol counteracts betamethasone-induced decrease in extracellular matrix 
components related to skin atrophy. Arch Dermatol Res. 2014;306(8):719-29. 
18. 
Menter A, Korman NJ, Elmets CA, Feldman S, Gelfand JM, Gordon KB, et al. 
Guidelines of care for the management of psoriasis and psoriatic arthritis Section 3. 
Guidelines of care for the management and treatment of psoriasis with topical therapies. J 
Am Acad Dermatol. 2009;60(4):643-59. 
19. 
Samarasekera E, Sawyer L, Parnham J, Smith CH. Assessment and management of 
psoriasis: summary of NICE guidance. BMJ. 2012;345:e6712. 
20. 
Hendriks AG, Keijsers RR, de Jong EM, Seyger MM, van de Kerkhof PC. Efficacy and 
safety of combinations of first-line topical treatments in chronic plaque psoriasis: a 
systematic literature review. J Eur Acad Dermatol Venereol. 2013;27(8):931-51. 
21. 
Fouere S, Adjadj L, Pawin H. How patients experience psoriasis: results from a European 
survey. J Eur Acad Dermatol Venereol. 2005;19 Suppl 3:2-6. 
22. 
Carroll C, Feldman S, Camacho FT, Balkrishnan R. Better medication adherence results 
in greater improvement in severity of psoriasis. Br J Dermatol. 2004;151(4):895-7. 
23. 
Therapeutics M. Investigational brochure, version 4 2018  


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24. 
LEO. Daivobet gel : Summary of Product Characteristics Updated 14-Jun 2018 
25. 
FDA. Taclonex Topical Suspension Prescribing Information 2017. 
26. 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - simple practical 
measure for routine clinical use. Clin Exp Dermatol. 1994;19(3):210-6. 
27. 
Rabin R, de CF. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 
2001;33(5):337-43. 
28. 
Lambert J, Hol CW, Vink J. Real-life effectiveness of once-daily calcipotriol and 
betamethasone dipropionate gel vs. ointment formulations in psoriasis vulgaris: 4- and 
12-week interim results from the PRO-long study. J Eur Acad Dermatol Venereol. 
2014;28(12):1723-31. 
29. 
Lambert J, Hol CW, Vink J. Real-life effectiveness of once-daily calcipotriol and 
betamethasone dipropionate gel vs. ointment formulations in psoriasis vulgaris: final 
analysis of the 52-week PRO-long study. J Eur Acad Dermatol Venereol. 
2015;29(12):2349-55. 
30. 
Menter A, Gold LS, Bukhalo M, Grekin S, Kempers S, Boyce BM, et al. Calcipotriene 
plus betamethasone dipropionate topical suspension for the treatment of mild to moderate 
psoriasis vulgaris on the body: a randomized, double-blind, vehicle-controlled trial. 
Journal of drugs in dermatology : JDD. 2013;12(1):92-8. 
31. 
Langley R, Gupta A, Papp K, Wexler D, Osterdal ML, Curcic D. Calcipotriol plus 
betamethasone dipropionate gel compared with tacalcitol ointment and the gel vehicle 
alone in patients with psoriasis vulgaris: a randomized, controlled clinical trial. 
Dermatology. 2011;222(2):148-56. 
32. 
Guenther L, van de Kerkhof PC, Snellman E, Kragballe K, Chu AC, Tegner E, et al. 
Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate 
(once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis 
vulgaris: a randomized, double-blind, vehicle-controlled clinical trial. Br J Dermatol. 
2002;147(2):316-23. 
33. 
Kragballe K, Noerrelund KL, Lui H, Ortonne JP, Wozel G, Uurasmaa T, et al. Efficacy 
of once-daily treatment regimens with calcipotriol/betamethasone dipropionate ointment 
and calcipotriol ointment in psoriasis vulgaris. Br J Dermatol. 2004;150(6):1167-73. 
34. 
Kragballe K, van de Kerkhof PC. Consistency of data in six phase III clinical studies of a 
two-compound product containing calcipotriol and betamethasone dipropionate ointment 
for the treatment of psoriasis. J Eur Acad Dermatol Venereol. 2006;20(1):39-44. 


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35. 
Ortonne JP, Kaufmann R, Lecha M, Goodfield M. Efficacy of treatment with 
calcipotriol/betamethasone dipropionate followed by calcipotriol alone compared with 
tacalcitol for the treatment of psoriasis vulgaris: a randomised, double-blind trial. 
Dermatology. 2004;209(4):308-13. 
 
 
 


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17.0 
APPENDICES 
 
17.1 
Appendix 1  
Contact List of MC2 and Protocol Authors  
Contact details for MC2 representatives are provided to the trial sites on a list outside the protocol, 
which is included in the clinical trial application.  
Sponsor 
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
c/o Agern Alle 24-26 
2970 Hoersholm 
DENMARK 
(“MC2”) 
 
Protocol Author 
Marianne Thrane, Medical Writer, Altrapharma ApS 
Johan Selmer, VP Medical Affairs, MC2 Therapeutics 
Birgitte Vestbjerg, Director Clinical Operation, MC2 Therapeutics 
Dorte Almstrup, Clinical Project Manager, MC2 Therapeutics  
Charlotte Hindsberger, Principal consultant, Biostatistics, S-cubed 
 
 
 
 


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17.2 
Appendix 2 
Vendors  
 
Responsible for all services related to the conduct of the trial:  
Proinnovera GmbH; Contract Organization for Clinical Research and Development, 
Wienburgstraße 207; 48159 Münster, Germany. 
 
Responsible for all services related to central laboratory analysis:  
MLM Medical Labs GmbH, 41066 Moenchengladbach, Germany. 
 
Responsible for all services related to packaging, labeling, distribution and destruction of the 
investigational medical products: IMP Pharmaceutical Services Ltd., Caerphilly, Wales NP12 
2DG, United Kingdom. 
 
Responsible for providing electronic data capture services: Data MATRIX Ltd., 14a Nekrasova 
Street, Let. A, 4th Floor, Saint-Petersburg, 191014, Russian Federation. 
 
Responsible for services related to SAE reporting and tracking, as specified in the contract: 
United BioSource Corporation (UBC), Chemin des Coquelicots 16, CH-1214 Vernier Geneva, 
Switzerland. 
  
 
 
 
 


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17.3 
Appendix 3 
Classification of Topical Corticosteroids - Examples 
Class 
Generic name and strength 
Brand name and formulation 
Class I 
Clobetasol Propionate 0.05% 
Dermovate Cream / Ointment / Scalp Application 
Diflucortolone Valerate 0.3% 
Nerisone Forte Oily Cream / Ointment 
Class II 
Beclometasone Dipropionate 0.025%   Generic Beclometasone Dipropionate Cream / Ointment 
Betamethasone Valerate 0.1% 
Betnovate Cream / Ointment / Lotion / Scalp Application 
Betamethasone Dipropionate 0.05% 
Diprosone Cream / Ointment / Lotion 
Diflucortolone Valerate 0.1% 
Nerisone Cream / Oily Cream / Ointment 
Fluocinolone Acetonide 0.025% 
Synalar Cream / Ointment / Gel 
Fluocinonide 0.05% 
Metosyn FAPG Cream / Ointment 
Fluticasone Propionate 0.05% 
Cutivate Cream 
Fluticasone Propionate 0.005% 
Cutivate Ointment 
Hydrocortisone Butyrate 0.1% 
Locoid Cream / Ointment / Scalp Lotion Locoid Crelo 
Emulsion 
Mometasone Furoate 0.1%   
Elocon Cream / Ointment / Scalp Lotion 
Triamcinolone Acetonide 0.1% 
Aureocort Ointment * 
Class III 
Alclometasone Dipropionate 0.05% 
Modrasone Cream 
Betamethasone Valerate 0.025% 
Betnovate-RD Cream / Ointment 
Clobetasone Butyrate 0.05% 
Eumovate Cream / Ointment 
Fludroxycortide 0.0125% 
Haelan Cream / Ointment 
Fluocinolone Acetonide 0.00625% 
Synalar 1 in 4 Dilution Cream / Ointment 
Fluocortolone 0.25% 
Ultralanum Plain Cream / Ointment 
Class IV 
Hydrocortisone 0.1-2.5% 
Generic Hydrocortisone Cream / Ointment Dioderm Cream 
Fluocinolone Acetonide 0.0025% 
Synalar 1 in 10 Dilution Cream 
 * Compound preparation (also contains chlortetracycline hydrochloride 3%); List of brand names and formulation is 
not exhaustive. 
 
 
 







SAP_001.pdf: 
MC2 Therapeutics 
Statistical Analysis Plan 
for 
Clinical Study Reporting 
of the Phase III Clinical Study MC2-01-C7 
A Randomized, Multicentre, Investigator-Blind, Parallel-Group Trial to 
Evaluate the Efficacy and Safety of MC2-01 Cream Compared to 
Vehicle and Active Comparator in Subjects 
 with Mild-to-Moderate Psoriasis Vulgaris 
FINAL Version 1.0 as of 7 October 2019 
 
Author: 
Frank Freischläger, Senior Principal Statistical Writer, Estimondo GmbH 
Contributor: Ladislav Pecen, Senior Principal Statistical Scientist, Estimondo GmbH 
For review and approval, see the MC2-01-C7 SAP for CSR Version 1.0 Review and Approval Sheet on 
file. 
Confidential 
Property of MC2 Therapeutics. May not be used, divulged, published or otherwise disclosed without the 
consent of MC2 Therapeutics. 
 
Document History 
Version 
Effective Date 
Description of Changes 
1.0 
7 Oct 2019 
New 
 
Table of Contents 
1 
Introduction .......................................................................................................................................... 4 
2 
Study Design and Objectives................................................................................................................ 5 
2.1 
Study Design ................................................................................................................................ 5 
2.2 
Treatments, Study Groups and Treatment Assignment ................................................................ 5 
2.3 
Study Objectives........................................................................................................................... 6 
2.3.1 
Primary Objectives ............................................................................................................... 6 
2.3.2 
Secondary Objectives ........................................................................................................... 6 
2.4 
Study Endpoints ........................................................................................................................... 6 


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2.4.1 
Efficacy Including Subject-Reported Outcomes .................................................................. 6 
2.4.2 
Safety and Tolerability ......................................................................................................... 9 
2.4.3 
Extent of Exposure and Study Treatment Compliance ...................................................... 11 
2.4.4 
Concomitant Therapies and Procedures ............................................................................. 12 
2.5 
Baseline Characteristics ............................................................................................................. 12 
2.5.1 
Baseline Disease Characteristics ........................................................................................ 12 
2.5.2 
Demographics ..................................................................................................................... 12 
2.5.3 
Concurrent Diagnoses and Medical History ....................................................................... 13 
2.5.4 
Previous Therapies and Procedures .................................................................................... 13 
2.5.5 
Vital Signs, Height and Weight at Baseline ....................................................................... 13 
3 
General Specifications for Analysis ................................................................................................... 13 
3.1 
Analysis Software....................................................................................................................... 13 
3.2 
Descriptive Statistics .................................................................................................................. 13 
3.2.1 
Summarizing Categorical Data ........................................................................................... 13 
3.2.2 
Summarizing Continuous Data........................................................................................... 13 
3.3 
Disposition of Subjects ............................................................................................................... 13 
3.4 
Premature Discontinuation of Treatment and/or Study Participation......................................... 14 
3.5 
Protocol Deviations .................................................................................................................... 14 
4 
Study Specifications for Analysis ...................................................................................................... 14 
4.1 
Interim Analysis ......................................................................................................................... 14 
4.2 
Analysis Populations .................................................................................................................. 14 
4.2.1 
Full Analysis Set ................................................................................................................ 14 
4.2.2 
Safety Set ............................................................................................................................ 14 
4.2.3 
Per-Protocol Set .................................................................................................................. 14 
4.2.4 
Usage of Analysis Populations ........................................................................................... 15 
4.3 
Subgroups and Confounding Factors for Analysis ..................................................................... 15 
4.4 
Time Points and Time Periods ................................................................................................... 15 
4.4.1 
Periods, Visits and Study Days .......................................................................................... 15 
4.4.2 
Dates ................................................................................................................................... 16 
4.4.3 
Identification of Baseline Values ....................................................................................... 16 
4.4.4 
Definitions of Change from Baseline ................................................................................. 16 
4.4.5 
Treatment Emergency of Adverse Events .......................................................................... 16 
4.4.6 
Treatment Relation of Concomitant Medication ................................................................ 16 
4.5 
Units and Unit Conversion ......................................................................................................... 16 
4.6 
Data Derivations ......................................................................................................................... 16 
4.6.1 
Durations ............................................................................................................................ 16 
4.6.2 
Analysis Visit Windowing ................................................................................................. 16 
4.6.3 
Classifications .................................................................................................................... 17 
4.6.4 
Notable Ranges ................................................................................................................... 17 


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4.7 
Handling of Missing Data and Data Imputation ......................................................................... 17 
4.7.1 
Partial Dates ....................................................................................................................... 17 
4.7.2 
Missing and Invalid Data.................................................................................................... 17 
5 
Statistical Methods ............................................................................................................................. 18 
5.1 
Conventions for Inference .......................................................................................................... 18 
5.2 
Statistical Hypotheses ................................................................................................................. 18 
5.3 
Overall Strategy and Issues of Multiplicity ................................................................................ 19 
5.4 
Approaches for Analysis ............................................................................................................ 20 
5.4.1 
Categorical Data ................................................................................................................. 20 
5.4.2 
Continuous Data ................................................................................................................. 20 
5.5 
Application of Methods .............................................................................................................. 20 
5.5.1 
Primary Efficacy Endpoint ................................................................................................. 21 
5.5.2 
Secondary Efficacy Endpoints ........................................................................................... 21 
5.5.3 
Other Efficacy Endpoints ................................................................................................... 22 
5.5.4 
Safety Endpoints ................................................................................................................. 23 
5.5.5 
Overview of Analyses ........................................................................................................ 23 
5.6 
Changes and Clarifications to Analyses Planned in the Study Protocol .................................... 24 
5.7 
Implementation ........................................................................................................................... 24 
6 
References .......................................................................................................................................... 24 
7 
Deliverables ........................................................................................................................................ 24 
7.1 
In-text Tables .............................................................................................................................. 25 
7.2 
In-text Figures ............................................................................................................................ 25 
7.3 
Post-text Tables .......................................................................................................................... 25 
7.4 
Post-text Figures ......................................................................................................................... 27 
7.5 
Statistical Output Documentation............................................................................................... 28 
7.6 
Data Listings............................................................................................................................... 28 
 
List of Tables 
Table 1: Overview of the meaning of mPASI scores assessed for arms, trunk and legs .............................. 7 
Table 2: Overview of intensity grading of local skin reaction by area and sign ........................................ 10 
Table 3: Definition of Notable Ranges of Vital Signs ............................................................................... 17 
Table 4: Overview on Hierarchical Hypothesis Testing Strategy with Different Endpoints and Hypotheses
 .................................................................................................................................................................... 19 
Table 5: Overview of analyses of endpoints for efficacy (with strategy, analysis set and imputation) ..... 23 
Table 6: Table of Content of Post-Text Tables .......................................................................................... 25 
Table 7: Table of Content of Post-Text Figures ......................................................................................... 28 
Table 8: Table of Content of Data Listings ................................................................................................ 28 
 


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List of Abbreviations and Acronyms 
Abbreviation 
Term 
ADaM 
Analysis Data Model 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
ATC 
Anatomic therapeutic chemical 
BSA 
Body surface area 
CDISC 
Clinical Data Interchange Standards Consortium 
CRF 
Case report form 
CSR 
Clinical study report 
CTP 
Clinical trial protocol 
DLQI 
Dermatology Life Quality Index 
EQ-5D 
EuroQOL five dimensions 
FAS 
Full analysis set 
ICH 
International Council on Harmonization 
IP 
Investigational product 
LOCF 
Last observation carried forward 
LSR 
Local skin reaction 
MCMC 
Markov Chain Monte Carlo  
MedDRA 
Medical dictionary for regulatory activities 
MI 
Multiple imputation 
mPASI 
Modified Psoriasis Area and Severity Index 
NRI 
Non-responder imputation 
PGA 
Physician’s Global Assessment 
PPS 
Per-protocol set 
PT 
Preferred term 
PTCS 
Psoriasis Treatment Convenience Scale 
QOL 
Quality of life 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SAS® 
Statistical Analysis System® 
SAS/STAT® 
SAS® Statistics software module 
SD 
Standard deviation 
SDTM 
Standard Data Tabulation Model 
SGA 
Subject global assessment of disease severity 
SOC 
System Organ Class 
TFL 
Tables, figures, listings 
TPA 
Tipping-point analysis 
VAS 
Visual analogue scale 
1 Introduction 
The Phase III trial MC2-01-C7 will be analyzed and reported in accordance with the clinical trial protocol 
(CTP) [1] and the International Conference on Harmonization (ICH) guidelines ICH E3 [2], ICH E6 [3] 
and ICH E9 [4]. MC2-01-C7 is a trial to compare the MC2 product in psoriasis vulgaris with a vehicle and 
an active comparator focusing on psoriasis on the body (trunk and/or limbs). 
This statistical analysis plan (SAP) should be read in conjunction with the CTP and the electronic case 
report form (CRF) [5]. This version of the plan has been developed using the CTP version 2.0 dated 16 
October 2018 and the SDTM-annotated CRF dated 15 August 2019. Any further changes to the protocol 
or CRF may necessitate updates to the SAP. 


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Based on this SAP, deliverables are derived analysis datasets following the CDISC ADaM standard, tables, 
figures and listings (TFL).  
2 Study Design and Objectives 
2.1 
Study Design 
This is a prospective, investigational, investigator-blind, vehicle and active-controlled, parallel-group, 3-
arm, randomized, phase-III trial conducted at approximately 34 sites in the European Union. The trial 
population consists of subjects fulfilling all inclusion and no exclusion criteria as defined in the CTP, 
Sections 5.2 and 5.3 with any exceptions documented [1]. Random allocation to one of three parallel 
treatment groups in a 3:1:3 ratio (MC2-01 cream; MC2-01 vehicle; active comparator) is stratified by site. 
A total of 476 subjects are planned to be enrolled, randomized and observed until final evaluation and 
completion. Subjects prematurely terminating the trial will not be replaced. 
The maximum trial duration for each subject will be approximately 14 weeks and includes a screening 
period of up to 30 days (if washout of prohibited medications is required), an 8-week treatment period, and 
a follow-up period of 2 weeks. 
A total of seven visits and a telephone interview of subjects are planned. The telephone interview is planned 
for Week 2 (Visit 3), while the visits will be held at screening (Visit 0, Day -30 to 0), randomization (Visit 
1, Week 0, Day 0), Visits 2, 4, and 5 at Weeks 1, 4 and 6, respectively, planned for Days 7, 28, and 42 
plus/minus 2 days, respectively, Visit 6 as end of treatment Visit (Week 8, Day 56+/-2, or at early 
termination), and Visit 7 as follow-up visit (Week 10, Day 70+/-2). The follow-up visit is planned as an 
on-site visit in case of abnormal laboratory values or unresolved adverse events (AE). Otherwise, the 
follow-up visit is a telephone interview. At any time during the trial, if judged necessary by the investigator, 
unscheduled visits may be performed. For a visit schedule, see CTP Section 7.0 [1]. 
2.2 
Treatments, Study Groups and Treatment Assignment 
Subjects will be randomly allocated to either receive MC2-01 cream, a combination product of calcipotriol 
and betamethasone, a MC2-01 vehicle or an active comparator, a marketed calcipotriol and betamethasone 
gel/topical suspension. Subjects apply the investigational product (IP) topically once daily preferable in the 
evening for 8 weeks to affected areas on the trunk (including the neck), the limbs, i.e., arms (including the 
back of the hands), the legs (including the buttocks and the top of the feet) and the scalp. 
Subjects should apply enough IP to treat the entire affected areas. Up to 4 tubes/bottles of 60 gram will be 
dispensed for a treatment period of 2 weeks including the allowed visit window of 2 days. The weekly dose 
is not to exceed 100 g, and the treated area should not exceed 30% of the body surface area (BSA).  
Subjects classified as clear at any of the on-treatment visits may stop the IP treatment at the investigator’s 
discretion. They should remain in the trial and attend all visits up to and including the follow-up visit. The 
IPs will continue to be dispensed to the subject, and IP treatment may be restarted at the subject’s discretion. 
The subjects should not discontinue IP treatment themselves between visits but are only allowed to stop 
using the IP treatment on the advice of the investigator at a scheduled visit. 
Subjects will be uniquely identified by a five-digit subject number composed of a two-digit site number, 
followed by three digits. The investigators and the entire study team will be kept blinded to treatment 
allocation information until the time of unblinding. Due to difference in formulation and packaging, it is 
not possible to double blind the IPs. A designated non-blinded staff member will be responsible for handling 
the IP (e.g. dispensing, returning, drug accountability). The investigators and the rest of the blinded study 
team will be kept blinded to treatment formulation information until the time of unblinding. 


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2.3 
Study Objectives 
2.3.1 
Primary Objectives 
The primary objective is to evaluate the efficacy of MC2-01 cream compared to active comparator in subjects 
with psoriasis vulgaris. 
2.3.2 
Secondary Objectives 
The secondary objective is to characterise the safety profile of MC2-01 cream in subjects with psoriasis 
vulgaris. 
2.4 
Study Endpoints 
In the following, endpoints are described by label, and by unit or valid categories. A categorical endpoint 
is of yes-no-type, if no categories are specified. A continuous or numerical endpoint is a score with or 
without a unit, if no unit is specified. 
2.4.1 
Efficacy Including Subject-Reported Outcomes 
The primary endpoint is the percentage change from baseline in the modified Psoriasis Area and Severity 
Index (mPASI) on the body (trunk and/or limbs) at Week 8. 
Based on a physician’s global assessment (PGA) and the Psoriasis Treatment Convenience Scale (PTCS), 
secondary endpoints include 
• 
PGA success on the body at Week 8, defined as a minimum 2-point decrease from baseline to Week 
8 on the PGA of psoriasis severity on the body (trunk and/or limbs) to a PGA of psoriasis severity 
of 0 (clear) or 1 (almost clear); i.e., a score of 0 (clear) or 1 (almost clear) for subjects with moderate 
disease at baseline; or a score of 0 (clear) for subjects with mild disease at baseline. 
• 
Subject assessment of treatment convenience at Week 8 using the PTCS total score, 
• 
Number of subjects with at least 75% reduction in mPASI from baseline (mPASI 75) on the body 
(trunk and/or limbs) at Week 8. 
• 
PGA success on the scalp at Week 8, defined as a minimum 2-point decrease from baseline to Week 
8 on the PGA of psoriasis severity on the scalp to a PGA of psoriasis severity of 0 (clear) or 1 
(almost clear); i.e., a score of 0 (clear) or 1 (almost clear) for subjects with severe or moderate 
disease at baseline; or a score of 0 (clear) for subjects with mild disease at baseline. 
Primary and secondary endpoints will be evaluated confirmatorily by hierarchical testing as described in 
Sections 5.2 and 5.3 below. Other endpoints will be exploratorily analyzed. 
Other endpoints include 
• 
Percentage change from baseline in mPASI score on the body (trunk and/or limbs) at Week 4, 
• 
mPASI 75 on the body (trunk and/or limbs) at Week 4, 
• 
PGA success on the body at Week 4,  
• 
PGA success on the scalp at Week 4, 
• 
Change from baseline in Subject Global Assessment (SGA) at Week 4 and Week 8, 
• 
Subject assessment of treatment convenience at Week 4 using the PTCS total score, 
• 
Change from baseline in the Dermatology Life Quality Index (DLQI) score at Week 4 and Week 
8, 
• 
Change from baseline in EQ-VAS at Week 4 and Week 8, 
• 
BSA involvement on the body and on the scalp at Week 4 and Week 8. 


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mPASI and mPASI 75 
At all on-site visits (Screening, Week 0, Week 1, Week 4, Week 6, Week 8, and Early Termination), the 
investigator will assess the extent and severity of the subjects’ psoriasis on the body (trunk and/or limbs) 
using an mPASI scoring system for each of the 3 areas (arms, trunk, and legs). The extent (E) is scored 0 
to 6. The severity of the psoriatic lesions in each of the 3 areas will be recorded for each of the signs of 
redness (R), thickness (T), and scaliness (S). For each clinical sign, a single score, reflecting the average 
severity of all psoriatic lesions on given body region, will be determined. Redness, thickness and scaliness 
scores are ranging from 0 to 4. The meaning of scores is summarized in the following table. 
Table 1: Overview of the meaning of mPASI scores assessed for arms, trunk and legs 
Score 
Extent (E) 
Redness  (R) 
Thickness (T) 
Scaliness (S) 
0 
no involvement 
none (no erythema) 
none (no plaque 
elevation) 
none (no scaling) 
1 
<10% 
mild (faint erythema, 
pink to very light red) 
mild (slight, barely 
perceptible elevation) 
mild (sparse, fine-
scale lesions, only 
partially covered) 
2 
10% to 29% 
moderate (definite 
light red erythema) 
moderate (definite 
elevation but not 
thick) 
moderate (coarser 
scales, most of 
lesions covered) 
3 
30% to 49% 
severe (dark red 
erythema) 
severe (definite 
elevation, thick 
plaque with sharp 
edge) 
severe (entire lesion 
covered with coarse 
scales) 
4 
50% to 69% 
very severe (very 
dark red erythema) 
very severe (very 
thick plaque with 
sharp edge) 
very severe (very 
thick coarse scales, 
possibly fissured) 
5 
70% to 89% 
- 
- 
- 
6 
90% to 100% 
- 
- 
- 
 
Per area, the scores for extent, redness, thickness and scaliness are combined to A = E  (R+T+S). Ranging 
from a minimum score of 0 and a maximum score of 64.8, the mPASI is calculated from the scores of the 
extent and severity of the disease by use of the following equation: 
 
mPASI = 0.2  Aarms + 0.3  Atrunk + 0.4  Alegs. 
At any post-baseline visit, mPASI 75 is defined as an indicator of a reduction in mPASI from baseline of 
75% or more. 
PGA and PGA Success on the Body and on the Scalp 
PGA measures the investigator’s impression of the disease at a single point using a defined, 5-point, static 
PGA scale (0 = clear, 1 = almost clear, 2 = mild, 3 = moderate or 4 = severe) at Screening, Weeks 0, 1, 4, 
6, 8, and Early Termination. 
The PGA assessment will be made separately for the body (trunk and/or limbs) and the scalp. It will 
represent the average lesion severity on the two body locations.  
At any post-baseline visit, PGA success is defined as a minimum 2-point decrease from baseline to the 
respective visit on the PGA of psoriasis severity to 0 (clear) or 1 (almost clear).  


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PTCS 
PTCS will be completed by the subjects before any other assessments are performed at Weeks 1, 4, 8, and 
Early Termination. 
The aim of PTCS is to assess the impact and convenience of psoriasis treatment. The scale consists of 6 
disease-specific, self-report questions rated on a 10-point scale ranging from 1 to 10. The questions are 
1. How easy was the treatment to apply to the skin? Answered by 1 = very difficult to 10 = very easy. 
2. How greasy was the treatment when applying it to the skin? Answered by 1 = very greasy to 10 = not 
greasy. 
3. How moisturised did your skin feel after applying the treatment? Answered by 1 = not moisturized to 
10 = very moisturized. 
4. How greasy did your skin feel after applying the treatment? Answered by 1 = very greasy to 10 = not 
greasy. 
5. How much did treating your skin disrupt your daily routine? Answered by 1 = very disturbing to 10 = 
not disturbing. 
6. Overall, how satisfied were you with the medical treatment? Answered by 1 = not satisfied to 10 = 
very satisfied. 
Ranging from 5 to 50, a PTCS total score is the sum of the scores on questions 1 to 5. If no more than two 
questions are answered, the PTCS total score is missing. If one or two questions remain unanswered, the 
missing scores are replaced by the average of the answered scores for the summation. 
SGA 
Subjects will grade the overall severity of their symptoms according to the following 5-point scale at Weeks 
0, 1, 4, 6, 8, and Early Termination: 
0 = Clear; no psoriasis symptoms at all. 
1 = Very mild; very slight psoriasis symptoms that do not interfere with daily life. 
2 = Mild; slight psoriasis symptoms that interfere with daily life only occasionally. 
3 = Moderate; definite psoriasis symptoms that interfere with daily life frequently. 
4 = Severe; intense psoriasis symptoms that interfere or restrict daily life very frequently. 
 
DLQI 
The DLQI is a validated questionnaire consisting of 10 questions relating to the degree to which the 
subject’s skin condition affected their daily activities, assessed at Weeks 0, 1, 4, 8, and Early Termination 
[6]. The questions are 
1. Over the last week, how itchy, sore, painful or stinging has your skin been? Answered by 0 = not at 
all to 3 = very much. 
2. Over the last week, how embarrassed or self-conscious have you been because of your skin? Answered 
by 0 = not at all to 3 = very much. 
3. Over the last week, how much has your skin interfered with you going shopping or looking after your 
home or garden? Answered by 0 = not at all/not relevant to 3 = very much. 
4. Over the last week, how much has your skin affected the clothes you wear? Answered by 0 = not at 
all/not relevant to 3 = very much. 
5. Over the last week, how much has your skin affected any social or leisure activities? Answered by 0 
= not at all/not relevant to 3 = very much. 
6. Over the last week, how much has your skin made it difficult for you to do any sport? Answered by 0 
= not at all/not relevant to 3 = very much. 


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7. Over the last week, has your skin prevented you from working or studying? Answered by no, 0 = not 
relevant or 3 = yes. If no, over the last week, how much has your skin been a problem at work or 
studying? Answered, by 2 = a lot, 1 = a little, 0 = not at all. 
8. Over the last week, how much has your skin created problems with your partner or any of your close 
friends or relatives? Answered by 0 = not at all/not relevant to 3 = very much. 
9. Over the last week, how much has your skin caused any sexual difficulties? Answered by 0 = not at 
all/not relevant to 3 = very much. 
10. Over the last week, how much of a problem has the treatment for your skin been, for example by 
making your home messy, or by taking up time? Answered by 0 = not at all/not relevant to 3 = very 
much. 
DLQI domain scores are defined as the sum of the scores on questions 1 and 2 as symptoms and feelings 
domain, questions 3 and 4 as daily activities domain, questions 5 and 6 as leisure domain, and questions 8 
and 9 as personal relationships domain, respectively. Work and school domain is covered by question 7, 
treatment domain by question 10. 
Ranging from 0 to 30, the DLQI score is the sum of the 10 scores. If one question remains unanswered, the 
missing score is replaced by 0 for the summation. If more than one question remains unanswered, the DLQI 
score is missing. 
EQ-5D 
The EQ-5D is intended to measure health-related quality of life (QOL) [7]. It consists of 5 items and a 
visual analogue scale (EQ-VAS). The EQ-VAS records the subject’s perceptions of their own current 
overall health scoring in a range from 0 to 100. The 5 self-assessment questions describe the subject’s 
current health in 5 dimensions i.e., mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. The items follow a 5-point Likert scale.  
BSA Involvement 
BSA involvement will be determined on the body, on the scalp and total as the extent (percentage) of 
subject’s psoriatic involvement on the total BSA at Week 0 (Day 0, Baseline), Week 4, Week 8, and at 
Early Termination. 
2.4.2 
Safety and Tolerability 
Local Skin Reaction 
Assessments of local skin reaction (LSR) will be performed by the investigator at all on-site post-screening 
visits. The treatment area and/or immediate surrounding for the following identified signs will be assessed: 
• 
Perilesional erythema, scaling, edema, atrophy, vesicles and erosion/ulceration; 
• 
Lesional vesicles, and erosion/ulceration. 
The intensity of each local skin reaction category is to be graded according to the scale in the following 
table. The most severe intensity observed for each category of the local skin reaction assessment is recorded. 
 
 


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Table 2: Overview of intensity grading of local skin reaction by area and sign 
Category 
 
Intensity 
 
 
 
Area 
Sign 
0 = absent 
1 = mild 
2 = moderate 
3 = severe 
Lesional 
Erosion/ 
ulceration 
none 
barely visible erosion 
distinct erosion 
Ulceration 
 
Vesicles 
none 
barely visible vesicles 
distinct vesicles 
Bullae 
Perilesional 
Erythema 
none 
barely visible erythema 
distinct erythema 
dark red erythema 
 
Scaling 
none 
barely visible scaling 
distinct scaling 
gross scales 
 
Edema 
none 
barely visible swelling 
easily palpable 
swelling 
gross swelling 
 
Atrophy 
none 
barely visible thinning 
distinct thinning 
Striae 
 
Vesicles 
none 
barely visible vesicles 
distinct vesicles 
Bullae 
 
Erosion/ 
ulceration 
none 
barely visible erosion 
distinct erosion 
Ulceration 
 
An LSR sum score is defined as the sum of intensity grades across all areas and signs per visit. Per sign, 
the most intense reaction is defined as the maximum intensity grade across visits. 
Adverse Events 
All adverse events (AE) are recorded with the following attributes: 
• 
severity (mild, moderate, severe), 
• 
location of AE to treatment area, 
• 
action taken (none, concomitant therapy, concomitant non-drug therapy), 
• 
action taken with IP (dose not changed, dose reduced, dose increased, dose interrupted, drug 
withdrawn, not applicable, unknown, other) 
• 
outcome (recovered, resolved with sequelae, recovering/ resolving, ongoing, death), 
• 
withdrawal due to AE, 
• 
start and end dates, 
• 
relationship to IP (definitely related, probably related, possibly related, not related), 
• 
relationship to study procedure, 
• 
seriousness, criterion for seriousness (death, life-threatening, hospitalization, disability/incapacity, 
congenital anomaly/birth defect, other). 
Any AE is treatment-emergent, if fulfilling the definition in Section 4.4.5. 
Any AE is a drug-related AE, if relationship to IP is not assessed as not related.  
Any AE is leading to drug withdrawal, if action taken with IP is drug withdrawn. 
Any AE is located in the treatment area, if location of AE to treatment area is inside treatment area or 
combined. 
Verbatim terms of the description of AEs will be coded according to MedDRA version 22.0 and classified 
according to preferred terms (PT) and primary system organ classes (SOC). 
Laboratory Parameters 
For all subjects, the following tests will be performed at Week 0 (Day 0, Baseline), Week 4 and Week 8, 
and at Early Termination: 
• Serum biochemistry: serum calcium (albumin corrected), serum albumin, serum alkaline 
phosphatase, serum phosphate, plasma parathyroid hormone, 25-OH Vitamin D (only at Week  0). 
• Urinalysis: urinary calcium, urinary phosphate, urinary calcium:creatinine ratio. 


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Laboratory parameters are reported in or converted to SI units [8]. According to normal ranges, laboratory 
values are categorized as abnormal low, within normal range, or abnormal high. 
During the course of the trial, urine pregnancy tests will be performed at Screening, Week 0, Week 4, Week 
8, and at Early Termination. 
Vital Signs 
Systolic and diastolic blood pressure, pulse rate and body temperature (oral or ear) will be measured at 
Week 0 (Day 0, Baseline), Week 4, Week 8, and at Early Termination. Values outside notable ranges will 
be flagged. For a definition of notable ranges, see Section 4.6.4 below. 
Physical Examination 
Abbreviated physical examination and complete dermatological examination will be assessed at Screening 
(Visit 0), Week 0 (Day 0, Baseline), Week 4, Week 8 and at Early Termination. In addition, height and 
weight are measured at Week 0 (baseline). 
2.4.3 
Extent of Exposure and Study Treatment Compliance 
Records of IP used, and dosages administered will be kept during the trial. The duration of study treatment 
is derived as the time in days from the date of first study drug application to the date of last study drug 
application. The extent of exposure in days is determined as the duration of study treatment minus the 
number of days without dosing. The number of days without dosing is derived from dose documentation 
between the date of first study drug application and the date of last study drug application. Days without 
dosing are days with reported non-administration. 
Subjects will be asked to return all used and unused tubes/bottles at each visit. All returned tubes/bottles that 
had been dispensed to a subject and are returned with a broken seal will be weighed to determine the amount 
of the IP used. 
The amount of drug used in grams is derived as the sum of the difference in drug weight dispensed and 
returned per kit. The total amount of drug used will be evaluated and also the amount used during the first 
week, the three weeks from Week 1 to Week 4, and the four weeks from Week 4 to Week 8. 
Duration of study treatment, extent of exposure, and amount of drug used will be presented by summary 
tables by treatment group. 
Treatment Compliance 
At all on-treatment visits, the subject will be asked if he/she has used the medication as prescribed. If this is 
not the case, the degree and nature of noncompliance will be collected in the CRF. In addition, subjects will 
be asked to complete a dosing diary during the treatment period as a measure of treatment compliance.  
On a daily basis in the dosing diary, if non-administration due to approved discontinuation is reported, 
treatment compliance is concluded, and if missed administration is reported, treatment non-compliance is 
concluded. 
For the entire treatment period to the Week 8 visit and for the periods from Week 0 to th Week 4 visit and 
from the Week 4 visit to the Week 8 visit, the percentage of treatment compliance is defined as 100 times 
the duration of the respective period minus the number of days with non-compliance divided by the duration 
of the respective period. Treatment compliance will be categorized to less than 80% versus 80% or more 
and to less than 70% versus 70% or more. 


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For the two periods, treatment compliance, as percentage and in categories, and non-administrations will 
be presented by summary tables by treatment group. 
2.4.4 
Concomitant Therapies and Procedures 
All therapies, including non-drug therapies, and procedures taken within 30 days prior to the start of and/or 
during the trial will be recorded at Screening and throughout the course of the trial. Information regarding 
the total daily dose, route of administration, start and discontinuation dates, location and indication are 
recorded. 
All verbatim terms of drug and non-drug therapies will be encoded according to the WHO Drug Dictionary 
version Q4/2018 and classified by PT and primary Anatomic Therapeutic Chemical (ATC) class level 2. 
All verbatim terms of procedures will be encoded according to MedDRA version 22.0. 
A therapy or procedure is concomitant, if not ending before or at Week 0 (Day 0, Visit 1) and not starting 
after the date of last study drug application. A therapy or procedure is post-treatment, if starting after the 
date of last study drug application. 
Per ATC level 2 and PT, frequencies of subjects with at least one concomitant therapy and at least one post-
treatment therapy will be presented by summary tables by treatment group and overall, respectively. 
2.5 
Baseline Characteristics 
2.5.1 
Baseline Disease Characteristics 
All patients suffer from mild to moderate psoriasis vulgaris on the body.  
At screening and at randomization, the trial population is described by 
• 
time in years since diagnosis, defined as the number of years from diagnosis to randomization at 
Week 0 (Visit 1), 
• 
Fitzpatrick Skin Type class at Screening (Visit 0), classified as I = pale white skin, blue/hazel eyes, 
blond/red hair, skin always burns and does not tan; II = fair skin, blue eyes, skin burns easily and 
tans poorly; III = darker white skin that tans after initial burn; IV = light brown skin that burns 
minimally and tans easily; V = brown skin that rarely burns and tans darkly easily; or VI = dark 
brown or black skin that never burns and always tans darkly, 
• 
previous psoriasis treatment per type of treatment, 
• 
BSA involvement on the body and on the scalp at Week 0 (Visit 1), 
• 
mPASI score at Week 0 (Visit 1), 
• 
PGA on psoriasis severity on the body and the scalp at Week 0 (Visit 1), 
• 
SGA on disease severity at Week 0 (Visit 1). 
Baseline disease characteristics will be presented by summary tables by treatment group and overall. 
Baseline disease characteristics will also be presented per country and per site. 
2.5.2 
Demographics 
At Screening, gender (male, female), year of birth, race (American Indian or Alaska Native, Asian, Black 
or African American, Native Hawaiian or Other Pacific Islander, White, other) and ethnic origin (Hispanic 
or Latino, not Hispanic or Latino) will be recorded. Age is derived in full years from birth to Screening.    
Demographics will be presented by summary tables by treatment group and overall. 


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2.5.3 
Concurrent Diagnoses and Medical History 
Entries of medical history, including concurrent diagnoses and surgeries, are recorded with start and end 
times. Verbatim terms of conditions, diagnoses and surgeries will be coded according to MedDRA version 
22.0 classified according to PTs and primary SOCs and presented in summary tables by treatment group 
and overall. Per primary SOC and PT, frequencies of subjects with at least one entry in the medical history 
and with at least one concurrent diagnosis will be displayed. An entry in the medical history is a concurrent 
diagnosis if ongoing at Screening. 
2.5.4 
Previous Therapies and Procedures 
Among recorded therapies and procedures (cp. Section 2.4.4), a therapy or procedure is previous if started 
before Week 0 (Visit 1).  
Per ATC level 2 and preferred name, frequencies of subjects with at least one previous therapy will be 
presented by summary tables by treatment group and overall. 
2.5.5 
Vital Signs, Height and Weight at Baseline 
Systolic and diastolic blood pressure, pulse rate and body temperature at Week 0 (Visit 1), height and 
weight from physical examination at Week 0 (Visit 1) and the body mass index, derived as weight in kg 
divided by the square of height in meters will be presented by summary tables by treatment group and 
overall. 
3 General Specifications for Analysis 
3.1 
Analysis Software 
All analyzes will be carried out on the Statistical Analysis System (SAS®) Analytics Pro, version 9.4 
including statistical procedures in the SAS/STAT® version 14.1 module [9]. 
3.2 
Descriptive Statistics 
All endpoints will be described using summary statistics for each treatment group, by visit where appropriate. 
3.2.1 
Summarizing Categorical Data 
Categorical including binary data will be summarized by means of frequency counts and percentages. The 
denominator of percentages will be indicated if ambiguous. All categories will be displayed in summary 
tables including those with zero counts. A category of missing counts will be added. 
3.2.2 
Summarizing Continuous Data 
Continuous data including scores will be summarized by means of arithmetic mean, standard deviation 
(SD), median, quartiles and ranges. Quartiles are given as (lower quartile, upper quartile) and ranges as 
(minimum, maximum). The number of non-missing values will also be displayed.  
3.3 
Disposition of Subjects 
A subject is screened if at least Visit 0 data are collected, randomized if Week 0 (Visit 1) data are collected 
and a randomization number given. 
Subject disposition will be summarized by the number (counts and percentages) of patients 


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• 
screened 
• 
failed screening 
• 
randomized 
• 
treated with an IP 
• 
prematurely discontinued treatment 
• 
completed treatment 
• 
prematurely discontinued trial 
Subject disposition will be summarized by treatment group and overall. Subject disposition will also be 
summarized per country and per site. 
3.4 
Premature Discontinuation of Treatment and/or Study Participation 
On subject disposition (see Section 3.3) counts and percentages will also be given by reason for screen 
failure and premature discontinuation of treatment and/or trial participation, respectively.  
3.5 
Protocol Deviations 
All observed protocol deviations will be listed. Following definitions in CTP Section 8.3 [1] and Section 
4.2.3 below, protocol deviations will be classified as major or minor in a minuted meeting for blind review 
of the database conducted prior to final database lock and unblinding. All protocol deviations and major 
protocol deviations will be presented in frequency tables. 
4 Study Specifications for Analysis 
4.1 
Interim Analysis 
No interim analysis is planned. 
4.2 
Analysis Populations 
4.2.1 
Full Analysis Set 
The full analysis set (FAS) includes all subjects randomly assigned to any IP following the intention-to-
treat principle. Subjects in the FAS are evaluated by treatment randomized to. 
4.2.2 
Safety Set 
The safety set consists of all randomized subjects, excluding subjects who return all the trial medication 
sealed. Subjects in the safety set are evaluated by treatment actually administered. 
4.2.3 
Per-Protocol Set 
The per-protocol set (PPS) includes all subjects of the FAS who complete the trial without major protocol 
deviations deemed to affect the primary endpoint analysis.  
If at least one major protocol deviation is observed in a subject of the FAS, the subject will be excluded 
from the PPS. Decisions on excluding subjects from the PPS will be taken and documented before 
unblinding the study. 
Subjects may be excluded from the PPS if any of the following criteria are met: 


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• 
Failure to meet key inclusion/exclusion criteria; i.e. deviation of inclusion/exclusion criteria that 
according to medical judgement may impact the primary endpoint analysis, 
• 
Usage of restricted medications/treatments; i.e. medications/treatments that according to medical 
judgement may impact the primary endpoint analysis, 
• 
Nonadherence to the visit schedule at Week 8: 49 to 66 days. 
• 
Noncompliance with the trial treatment regimen; adherence to the treatment schedule defined as 
application of the randomized IP as specified by the investigator for at least 80% of the days from 
Week 0 to Week 8 visit, and at least 80% of the days from Week 4 visit to Week 8 visit. 
4.2.4 
Usage of Analysis Populations 
The FAS will be used as randomized for all efficacy analyses. As randomized, the PPS will only be used 
in sensitivity analyses for the non-inferiority evaluations and for the PTCS score evaluation. PGA success 
on the scalp will only be analyzed in subjects that at Week 0 (Visit 1) has a PGA of psoriasis severity on 
the scalp assessed as at least mild and a scalp involvement of at least 0.3% BSA. 
Safety endpoints will be analyzed in the safety set as treated, i.e. by trial medication actually taken. 
Demographics and baseline disease characteristics will be described for the FAS, the safety set and the PPS. 
Other baseline characteristics, exposure and concomitant therapies will be described for the FAS. 
4.3 
Subgroups and Confounding Factors for Analysis 
No subgroup analysis will be done.  
The potential confounding by trial sites will be considered by adjustment in statistical models. By country, 
trial sites with less than 14 FAS subjects will be pooled to form analysis sites. For trial sites with 14 FAS 
subjects or more, the trial site will be the analysis site.  
The potential confounding by PGA at baseline will be considered by adjustment in all statistical models. 
Depending on the endpoint as described below, the analysis may be adjusted by further confounding factors, 
particularly the baseline values of the respective endpoints in the models as covariates. 
4.4 
Time Points and Time Periods  
4.4.1 
Periods, Visits and Study Days 
The screening period will last from Screening (Visit 0) to randomization (Visit 1/Week 0, Day 0). The 
treatment period will last from randomization (Visit 1/Week 0) to end of treatment (Visit 6/Week 8 or Early 
Termination). The follow-up period will last from end of treatment (Visit 6/Week 8) to end of follow-up 
(Visit 7/Week 10). 
Up to six on-site visits are scheduled per subject, at Screening (Visit 0), and Weeks 0, 1, 4, 6 and 8. Visit 
1/Week 0 is Day 0, the reference date. In addition, at Week 2, there is a telephone contact planned. Another 
on-site visit, or a telephone interview, will be held at end of follow-up. Further unscheduled visits may be 
done as deemed necessary. 
Per visit, actual study days will be derived as the time passed in number of days since the reference date 
plus 1. 


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4.4.2 
Dates 
The date of Visit 1 is the reference date, Day 0. Start and end dates, and the dates of last study drug 
application and last contact will be related to Day 0, given as study day. Negative study days indicate dates 
before Visit 1. 
It is assumed that treatment in the treatment period occurs from the evening of Day 0 to the day before Visit 
6 (Week 8) unless otherwise reported. 
4.4.3 
Identification of Baseline Values 
Per variable, baseline values are the values reported at randomization (Visit 1/Week 0, Day 0). If values at 
randomization are missing, values at Screening (Visit 0) are considered as baseline values. 
4.4.4 
Definitions of Change from Baseline 
Changes from baseline are defined as post-baseline value minus baseline value. Reductions are negative 
changes. Percentage changes from baseline are defined as 100 times changes from baseline divided by the 
baseline value.  
4.4.5 
Treatment Emergency of Adverse Events 
An AE is treatment-emergent if it occurs or deteriorates at or after the first application of the IP. Otherwise, 
an AE is not treatment-emergent.  
4.4.6 
Treatment Relation of Concomitant Medication 
A medication or therapy is related to treatment by timing. It is concomitant or post-treatment as defined in 
Section 2.4.4 above. 
4.5 
Units and Unit Conversion 
Dates are recorded by day, month and year. For imputation of partial dates, see Section 4.7.1 below. Days 
are calculated following rules in Sections 4.4.1, 4.4.2 and 4.6.1. 
It is assumed that no unit conversion is required. Laboratory data will be reported in or converted to SI units  
[8]. 
4.6 
Data Derivations 
For the derivation of total and sum scores in efficacy endpoints see Section 2.4.1 above. Age, in full years, 
is derived as the number of calendar years from year of birth to the year of screening. 
4.6.1 
Durations 
Time durations, i.e. lengths of time periods, will be derived as end date minus start date plus 1 day in days. 
4.6.2 
Analysis Visit Windowing 
Post-baseline visits are to be held at Weeks 1, 2, 4, 6, 8 and 10, namely at study Day 7, 14, 28, 42, 56 and 
70, within two days from target day. In addition, unscheduled visits and visits of Early Termination may 
be given. Comprehensive non-overlapping visit windows are defined for Week 4 from Day 14 to Day 42 
and for Week 8 as Day 43 or later, respectively, excluding any follow-up visits. 


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Primary and secondary efficacy endpoints will be summarized and analysed by analysis visits. For Week 4 
and Week 8, analysis visits are defined as the visits held closest to the target day per analysis visit window 
as defined above. Any other visits within the same visit window will not be considered for analysis of 
primary or secondary efficacy endpoints. If the time distances of two visits from the target day are identical, 
the later visit is selected for analysis. 
Other efficacy endpoints and safety endpoints will be summarized and analysed by nominal visits as 
appropriate. 
4.6.3 
Classifications 
Laboratory parameter values are abnormal low, if below the normal range, normal if within the normal 
range and abnormal high if above the normal range. 
4.6.4 
Notable Ranges 
Notable ranges are defined for vital signs according to Table 3. Notable values are post-treatment values 
outside the notable ranges, whether above or below, and are indicated as notably abnormal. 
Table 3: Definition of Notable Ranges of Vital Signs 
Parameter 
Notable Values and Changes from Baseline 
Systolic blood pressure 
90 mmHg or lower and decreased by 20 mmHg or more,  
180 mmHg or greater and increased by 20 mmHg or more 
Diastolic blood pressure 
50 mmHg or lower and decreased by 15 mmHg or more,  
110 mmHg or greater and increased by 15 mmHg or more 
Pulse rate 
50 bpm or lower and decreased by 15 bpm or more, 
120 bpm or greater and increased by 15 bpm or more 
 
4.7 
Handling of Missing Data and Data Imputation 
4.7.1 
Partial Dates 
If a date relevant for analysis is only partially available, it will be imputed by the central day of the time 
period of uncertainty, if this rule will be in line with potential dependencies of other complete dates in 
chronology. The time period of uncertainty is, for example, the calendar month, if the day is missing, or the 
calendar year, if day and month are missing. If the imputed date must be before or after a reference date, or 
between two reference dates, and the central day of the time period of uncertainty would not, the date will 
be imputed by the day of the time period of uncertainty closest to the central day but fulfilling the 
dependencies. 
The approach of partial date imputation will be applied to visit dates, start and end dates of adverse events, 
start and end dates of concomitant medication, and the dates of last study drug application and of last 
contact, if partial. 
4.7.2 
Missing and Invalid Data 
Data is missing if unavailable. Data is invalid if not considered for analysis. Invalidity of data is defined 
below, where applicable. On some analyses as indicated below, missing or invalid data will be replaced by 
the last observation carried forward (LOCF), by non-responder imputation (NRI) or by multiple imputation 
(MI). 


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Single Imputation by LOCF 
On LOCF, a missing value is imputed by the last available value carried forward to the visit with the value 
missing until and including the last visit. 
Single Imputation by NRI 
On NRI, a missing value is imputed by a value representing non-response. Non-response is defined per 
endpoint below. 
Multiple Imputation 
Post-baseline missing or invalid data will be multiply imputed within treatment groups in two steps [10]. 
At first, any potential intermediate missing data will be imputed 100 times using a Markov Chain Monte 
Carlo (MCMC) method to obtain a monotone missing data pattern. In a second step, imputation is done 
using a monotone regression method, fitting an analysis of covariance (ANCOVA) model stepwise visit by 
visit. The ANCOVA model adjusts for the effects of analysis sites and baseline PGA as factors and the 
baseline value of the respective endpoint as a covariate. For each treatment group and each copy of the 
dataset, the estimated parameters and their variances are used to impute the endpoint. Starting with Week 
1, the procedure is repeated on Week 4, Week 6 and Week 8, adding the possibly imputed values of the 
previous visits as covariates. On MI, missing score data is handled like missing continuous data. 
If MI is applied to a dichotomized endpoint, the procedure is followed before dichotomization. 
For analyses on the PPS or the safety set, no imputations will be made for missing data. For analyses on 
the FAS, LOCF, NRI and MI will be made for missing and invalid data. 
5 Statistical Methods 
5.1 
Conventions for Inference 
The two-sided level of significance is set to  = 0.05, the one-sided level of significance to  = 0.025.  
5.2 
Statistical Hypotheses 
Let M, V and C be estimators of treatment effect per endpoint for MC2-01 cream, MC2-01 cream vehicle 
and active comparator, respectively. The following four statistical hypotheses will be tested. 
a. H0a: M = V versus H1a: M  V,  
b. H0b: C = V versus H1b: C  V,  
c. H0c: M - C  - versus H1c: M - C > -, 
d. H0d: M = C versus H1d: M  C. 
where  is a non-inferiority margin. In two-sided H0a, H0b and H0d, if the hypothesis is rejected, superiority 
of the group with greater estimate is concluded. On one-sided H0c, if the lower limit of the two-sided 95% 
confidence interval of the estimate of the treatment difference is greater than -, non-inferiority of MC2-
01 cream as compared to active comparator is concluded. 
The non-inferiority margin  is 12 percentage points on the primary endpoint mPASI and 10 percentage 
points on the first secondary endpoint PGA success. 


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5.3 
Overall Strategy and Issues of Multiplicity 
The statistical hypotheses on the primary and secondary endpoints will be tested confirmatorily in a 
hierarchical approach. The hierarchical approach ensures that the familywise type 1 error is controlled. 
According to the definitions in Section 5.2, hypotheses will be hierarchically tested starting with H0a and 
H0b. If, and only if H0a and H0b are, H0c is tested confirmatorily. Hierarchical testing, H0a to H0c, will be 
done on the primary endpoint, mPASI, at first. If, and only if, non-inferiority of MC2-01 cream versus 
active comparator is claimed on the primary endpoint, the hierarchical testing procedure is continued on 
the first secondary endpoint, PGA success on the body. If, and only if, non-inferiority of MC2-01 cream 
versus active comparator is claimed on the first secondary endpoint, H0d is tested on the second secondary 
endpoint, PTCS, on the primary endpoint, the first secondary endpoint, the third secondary endpoint, 
mPASI 75, where also H0a is tested, and the fourth secondary endpoint, PGA success on the scalp, if, and 
only if, leading to rejections on the previous steps. In case hypotheses cannot be rejected, testing on this 
and all preceding hypotheses is exploratory only. The strategy is summarized in the following display. 
Table 4: Overview on Hierarchical Hypothesis Testing Strategy with Different Endpoints and Hypotheses 
Endpoint 
Step 
Hypothesis 
%change in mPASI at Week 8 
1 
H0a for superiority of MC2-01 cream over vehicle 
 
2 
H0b  for superiority of active comparator cream over vehicle 
 
3 
H0c for non-inferiority of MC2-01 cream and active comparator 
PGA success on the body at Week 8 
4 
H0a for superiority of MC2-01 cream over vehicle 
 
5 
H0b for superiority of active comparator cream over vehicle 
 
6 
H0c for non-inferiority of MC2-01 cream and active comparator 
PTCS at Week 8 
7 
H0d for superiority of MC2-01 cream over active comparator 
%change in mPASI at Week 8 
8 
H0d for superiority of MC2-01 cream over active comparator 
PGA success on the body at Week 8 
9 
H0d for superiority of MC2-01 cream over active comparator 
mPASI 75 at Week 8 
10 
H0a for superiority of MC2-01 cream over vehicle 
 
11 
H0d for superiority of MC2-01 cream over active comparator 
PGA success on the scalp at Week 8 
12 
H0a for superiority of MC2-01 cream over vehicle 
 
13 
H0d for superiority of MC2-01 cream over active comparator 
For definitions of hypotheses, see Section 5.2 
Efficacy endpoints will be analyzed by different estimands, following a treatment-policy strategy (primary 
estimand) and a hypothetical strategy (secondary estimand). Only on PTCS, a while-on-treatment strategy 
will be followed. 
According to the treatment-policy strategy, all available data will be used, regardless of treatment and 
treatment adherence. Missing data will be imputed. 
According to the hypothetical strategy, only data will be used under the IP and while adhering to the IP. If 
any other psoriasis treatment is used, i.e. treatment that according to medical judgement may improve 
psoriasis, data during and after the period of other psoriasis treatment intake is invalid and will not be used. 
Furthermore, data will not be used of periods of potential non-adherence to the IP. Non-adherence will be 
given if the IP is applied on less than 70% of the days from Day 0 to Week 4, Week 4 to Week 6, and Week 
6 to Week 8, respectively. Non-adherence to the IP is derived from days with treatment non-compliance. 
Missing and invalid data will be imputed. 
According to the while-on-treatment strategy, all available data will be used with treatment within 7 days 
before assessment. Data without treatment within 7 days before assessment is invalid and will not be used. 
Hierarchical testing applies to the primary analyses per endpoint, not to any sensitivity analyses as described 
below. 


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5.4 
Approaches for Analysis 
All collected, recorded and derived data for analysis will be listed in individual subject data listings. On 
vital signs, notably abnormal values will be flagged. 
5.4.1 
Categorical Data 
Categorical data will be described by summary tables of counts and percentages. This includes zero counts 
of all possible categories, if any. Selected categorical variables will be visualized by bar charts by treatment 
group and visit. 
Logistic Regression 
Selected binary endpoints will be analysed using a logistic model with effects of treatment, analysis site, and 
the baseline value of the endpoint as factors. The estimated log odds ratios between the treatments at Week 
8 will be derived together with the associated standard error and 95% confidence intervals. 
Logistic regression is used for superiority testing only. The non-inferiority analysis is done without 
modelling by means of unadjusted risk differences between treatment groups. 95% confidence intervals 
will be computed using normal approximation. 
5.4.2 
Continuous Data 
Continuous data will be described by summary tables of sample characteristics by visit and for changes 
between visits as defined in Section 3.2.2 above. Selected continuous variables will be visualized by box 
plots by treatment group and visit. 
ANCOVA 
Comparisons will be done using an ANCOVA model including treatment, analysis site and baseline PGA 
as factors, and the baseline value of the respective endpoint as covariate.  
The statistical model is 
 
endpoint = 0 + 1baseline value + treatment + analysis site + baseline PGA + error, 
where 1 is a parameter of fixed effect and 0 an intercept. The estimated differences between MC2-01 
cream and MC2-01 cream vehicle, and between active comparator and MC2-01 cream vehicle, will be 
reported together with the associated standard error, the 95% confidence interval, and a p-value of a test on 
the respective contrast corresponding to the hypothesis as either no difference between treatments 
(superiority) or difference between treatments within the tolerance limits (non-inferiority) (cp. Section 5.2 
above). 
5.5 
Application of Methods 
Statistical hierarchical testing will be applied as described in Sections 5.2, 5.3 and 5.4.2. The following 
subsections describe the application of methods per endpoint, summarized in Section 5.5.5.  
Multiple Imputation Procedure 
Applicable to all endpoints with MI, the procedural steps are as follows. On 100 multiple complete imputed 
datasets as produced according to the instructions in Section 4.7.2, each dataset will be analyzed the same 
way. After pooling the estimates and standard errors, results will be aggregated following Rubin’s rule to 
yield one estimate and associated standard error, and to calculate the 95% confidence interval for the 


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treatment difference or odds ratio between treatments, respectively [11]. In data listings, multiply imputed 
values are described by mean values. 
5.5.1 
Primary Efficacy Endpoint 
The primary endpoint, percentage change in mPASI on the body (trunk and/or limbs) from baseline to 
Week 8, will be analysed for superiority and non-inferiority by means of ANCOVA as described in Section 
5.4.2. 
Primary Analysis 
The primary analysis is for superiority of MC2-01 cream versus MC2-01 cream vehicle and of active 
comparator versus MC2-01 cream vehicle as well as for non-inferiority of MC2-01 cream and active 
comparator using the treatment-policy strategy on the FAS using MI to impute missing data. The estimated 
pairwise differences will be reported together with the associated standard error, the 95% confidence 
interval, and p-values of testing hypotheses H0a, H0b and H0c. 
Sensitivity Analyses 
Three sensitivity analyses are planned on the primary endpoint, for internal validity a tipping-point analysis 
following the treatment-policy strategy on the FAS using MI, for external validity an analysis following 
the hypothetical strategy on the FAS using MI, and an analysis following the treatment-policy strategy on 
the PPS. 
Tipping-point analysis for treatment-policy strategy on the FAS 
The primary analysis of mPASI using MI assumes that data are missing at random (MAR) within each 
treatment arm. For each hypothesis, the sensitivity of the MAR assumption is investigated using a tipping-
point analysis [10]. A penalty (a number) is added to all imputed Week 8 values in the MC2-01 cream treatment 
group or (when testing superiority of active comparator vs. vehicle) in the active comparator group, and the 
analysis is repeated on the FAS for the treatment-policy estimand as described for the primary analysis. The 
penalty is gradually increased until the point, the tipping point, where the conclusion (superiority or non-
inferiority depending on the analysis) no longer is demonstrated. The tipping point will be reported. If the 
tipping point is considered a clinical plausible difference, the tipping-point analysis does not support the 
primary analysis. 
Hypothetical strategy on the FAS 
mPASI is analysed following the hypothetical strategy as described in Section 5.3 on the FAS using MI for 
missing and unused data as described in Section 4.7.2. 
Treatment-policy strategy on the PPS 
mPASI is analysed following the treatment-policy strategy as in the primary analysis, but on the PPS 
without using any imputation approach. 
5.5.2 
Secondary Efficacy Endpoints 
If the primary analysis of the primary endpoint yields rejection of all hypotheses, hierarchical testing is 
continued on secondary efficacy endpoints, with PGA success at first, followed by PTCS. 
PGA Success 
The first and fourth secondary efficacy endpoints are the percentage of subjects with PGA success on the 
body and on the scalp at Week 8, respectively, as defined in Section 2.4.1. 


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Primary Analysis 
Considering PGA as a continuous endpoint, missing data will be imputed using MI as described in Section 
4.7.2. On derived PGA success following the treatment-policy strategy, hypotheses will be tested, and 
comparisons of treatment groups done using a model of logistic regression as described in Sections 5.2 and 
5.4.1. 
Sensitivity Analyses 
Two sensitivity analyses are planned on the first secondary endpoint, an analysis following the treatment-
policy strategy on the FAS using NRI, and an analysis following the hypothetical strategy on the FAS using 
MI. On PGA success, non-response is defined as no PGA success. 
In a first sensitivity analysis, missing data will be imputed using NRI as described in Section 4.7.2. On 
PGA success following a treatment-policy strategy, hypotheses will be tested, and comparisons of treatment 
groups done using a model of logistic regression as described in Sections 5.2 and 5.4.1. 
In a second sensitivity analysis, missing and unused data will be imputed using MI as described in Section 
4.7.2. On PGA success following a hypothetical strategy, hypotheses will be tested, and comparisons of 
treatment groups done using a model of logistic regression as described in Sections 5.2 and 5.4.1. 
PTCS 
The second secondary efficacy endpoint is the PTCS total score at Week 8. The PTCS total score will be 
analysed by means of an analysis of variance with treatment, analysis site and baseline PGA as factors.  
Analysis of PTCS is following a while-on-treatment strategy using data as described in Section 5.3. Missing 
and invalid data will be imputed using LOCF as described in Section 4.7.2. 
Primary Analysis 
The primary analysis of PTCS will be based on the FAS following the while-on-treatment approach using 
LOCF to impute missing and invalid data. 
Sensitivity Analyses 
A sensitivity analysis of PTCS will be based on the PPS following the while-on-treatment approach using 
LOCF to impute missing and invalid data. 
mPASI 75 
mPASI 75 at Week 8 will be analyzed on the FAS like PGA success at Week 8 including mPASI at baseline 
as a covariate. 
5.5.3 
Other Efficacy Endpoints 
Efficacy and subject-related outcomes will be exploratorily analyzed on the FAS at Week 4 as described 
for Week 8 above, without formal statistical hypothesis testing. 
PGA success at Week 4 and mPASI 75 at Week 4 will be analyzed on the FAS like PGA success at Week 
8 including mPASI at baseline as a covariate (cp. Section 5.4.1). 
Observed changes from baseline in SGA at Week 4 and Week 8, and changes from baseline in BSA 
involvement on the body and the scalp will be presented descriptively on the FAS. 


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DLQI domain and total scores will be summarized by visit including changes from baseline on the FAS. 
Changes from baseline in the DLQI total score at Week 4 and Week 8 will be analyzed on the FAS by 
means of ANCOVA as described in Section 5.4.2 utilizing MI. Imputations will be made on the domain 
level to derive the DLQI total score. 
Observed EQ-5D dimension assessments and VAS score will be summarized by visit on the FAS. Changes 
from baseline in EQ-VAS score at Week 4 and Week 8 will be analyzed on the FAS by means of ANCOVA 
as described in Section 5.4.2 utilizing MI. 
5.5.4 
Safety Endpoints 
Safety endpoints will be described by summary tables on the safety set. 
Treatment-emergent AEs, treatment-emergent drug-related AEs, treatment-emergent serious AEs (SAE), 
treatment-emergent drug-related SAEs, treatment-emergent AEs leading to drug withdrawal and treatment-
emergent drug-related AEs leading to drug withdrawal will be presented in summary tables of the number 
and percentage of patients with at least one event, and the number of events, by primary SOC and by PT 
within SOC. For treatment-emergent AEs and treatment-emergent drug-related AEs, these summaries will 
also be provided by maximum severity. Maximum severity is defined by the most severe AE per subject, 
SOC and PT. 
Local skin reaction sum scores, vital signs and laboratory parameters will be summarized by visit including 
changes from baseline. Frequencies of most intense local skin reactions will also be presented.  
Using normal ranges, laboratory parameters will be presented in shift tables of frequencies of all categorized 
post-baseline versus categorized baseline values per visit (cp. Section 4.6.3).  
5.5.5 
Overview of Analyses 
Analyses of safety endpoints are descriptive and exploratory. Planned analyses of primary, secondary and 
other endpoints for efficacy, including subject-related outcomes, are summarized in the following table. 
Table 5: Overview of analyses of endpoints for efficacy (with strategy, analysis set and imputation) 
Sequence 
Endpoint 
Primary Analysis 
Sensitivity Analyses 
Primary 
%change in mPASI at W8 
treatment policy, FAS, MI 
1: treatment policy, FAS, MI, TPA; 
2: hypothetical, FAS, MI; 
3: treatment policy, PPS 
Secondary 
PGA success on the body at 
W8 
treatment policy, FAS, MI 
1: treatment policy, FAS, NRI; 
2: hypothetical, FAS, MI 
 
PTCS* at W8 
while on treatment, FAS, 
LOCF 
while on treatment, PPS, LOCF 
 
mPASI 75 
treatment policy, FAS, MI 
- 
 
PGA success on the scalp at 
W8 
treatment policy, FAS, MI 
1: treatment policy, FAS, NRI; 
2: hypothetical, FAS, MI 
Other** 
%change in mPASI at W4 
treatment policy, FAS, MI 
- 
 
PTCS at W4 
while on treatment, FAS, 
LOCF 
- 
 
Change in DLQI 
treatment policy, FAS, MI 
- 
 
Change in EQ-VAS 
treatment policy, FAS, MI 
- 
* for superiority of MC2-01 cream versus active comparator, ** additionally EQ-5D, SGA and BSA involvement 
   descriptively only 
TPA = tipping-point analysis, W = Week 
On primary analysis, for an overview on hierarchical testing of statistical hypotheses on the primary 
endpoint and the secondary endpoints, see Table 4 in Section 5.3. 


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5.6 
Changes and Clarifications to Analyses Planned in the Study Protocol 
Analyses are planned according to protocol. Defined as other endpoints in the protocol, mPASI75 at Week 
8 and PGA of psoriasis severity on the scalp at Week 8 are promoted to secondary endpoints at the end of 
the hierarchical testing strategy on secondary endpoints. For PGA on the scalp, the same definition of PGA 
success as on the body will be applied, on a subpopulation of subjects with psoriasis on the scalp at baseline. 
To clarify, BSA assessment is listed under other endpoints. Notable laboratory normal ranges will not be 
defined. 
5.7 
Implementation 
The SAP will be implemented by means of statistical programming specifications with technical details of 
implementation and the level of validation of programming. Derived datasets will be produced following 
raw-to-derived data specifications, tables, figures and listings (TFL) according to approved TFL shell 
versions. 
6 References 
[1] MC Therapeutics: Clinical Trial Protocol, Version 2.0, dated 16 October 2018. 
[2] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (1995). Topic E3. Structure and Content of Clinical Study Reports. 
[3] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (2016). Integrated Addendum to ICH E6(R1): Guideline for Good Clinical Practice. Topic 
E6(R2). Guideline for Good Clinical Practice. 
[4] International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human 
Use (1998). Topic E9. Statistical Principles for Clinical Trials. 
[5] MC Therapeutics: Case Report Form, Version 2.0, dated 21 January 2019. 
[6] Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - simple practical measure for routine 
clinical use. Clin Exp Dermatol. 1994;19(3):210-6. 
[7] Rabin R, de CF. EQ-5D: a measure of health status from the EuroQol Group. Ann Med. 
2001;33(5):337-43. 
[8] Kratz A, Ferraro M, Sluss PM et al. (2004): Laboratory reference values. N Engl J Med 351: 1548-63.  
[9] SAS Institute Inc. SAS/STAT® 14.1 User’s Guide. SAS Institute Inc. 2016. 
[10] O'Kelly M, Ratitch B (2014): Clinical Trials with Missing Data: A Guide for Practitioners. Wiley, 
Chichester, UK. 
[11] Rubin DB. Multiple Imputation for Nonresponse in Surveys. New York, NY, USA: Wiley & Sons; 
1987. 
7 Deliverables 
Based on a TFL shells document, the following tables, figures and listings will be produced. 


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7.1 
In-text Tables 
In-text tables will be produced identical to selected post-text tables by content and in the layout of the 
report. 
7.2 
In-text Figures 
In-text figures will be copied from selected post-text figures. 
7.3 
Post-text Tables 
The following post-text tables will be produced. All tables will summarize results by treatment group. 
Table 6: Table of Content of Post-Text Tables 
14.1 
Disposition, Baseline Characteristics, Exposure and Concomitant Therapies 
Table 14.1.1.1 
Subject Disposition – Summary 
Table 14.1.1.2 
Subject Disposition – Summary by Country 
Table 14.1.1.3 
Subject Disposition – Summary by Site 
Table 14.1.2 
Analysis Sets – Summary 
Table 14.1.3.1 
Inclusion and Exclusion Criteria – Summary 
Table 14.1.3.2 
Protocol Deviations – Summary 
Table 14.1.3.3 
Major Protocol Deviations – Summary 
Table 14.1.4.1 
Demographics – Summary on the FAS 
Table 14.1.4.2 
Demographics – Summary on the Safety Set 
Table 14.1.4.3 
Demographics – Summary on the PPS 
Table 14.1.5.1 
Baseline Disease Characteristics – Summary on the FAS 
Table 14.1.5.2 
Baseline Disease Characteristics – Summary on the Safety Set 
Table 14.1.5.3 
Baseline Disease Characteristics – Summary on the PPS 
Table 14.1.5.4 
Baseline Disease Characteristics – Summary by Country on the FAS 
Table 14.1.5.5 
Baseline Disease Characteristics – Summary by Site on the FAS 
Table 14.1.6 
Vital Signs, Height and Weight at Baseline – Summary on the FAS 
Table 14.1.7.1 
Medical History – Summary by SOC and PT on the FAS 
Table 14.1.7.2 
Concurrent Diagnoses at Screening – Summary by SOC and PT on the FAS 
Table 14.1.8.1 
Previous Drug Therapies – Summary by ATC Class and PT on the FAS 
Table 14.1.8.2 
Concomitant Drug Therapies – Summary by ATC Class and PT on the FAS 
Table 14.1.8.3 
Post-Treatment Drug Therapies – Summary by ATC Class and PT on the FAS 
Table 14.1.9 
Exposure and Treatment Compliance - Summary on the FAS 
14.2 
Efficacy Data 
14.2.1 
Primary Efficacy Endpoint 
Table 14.2.1.1 
mPASI – Summary by Visit on the FAS, Observed Cases 
Table 14.2.1.2 
mPASI Score – Summary by Visit on the FAS, Averaged Multiple Imputations, Treatment-
policy Strategy 
Table 14.2.1.3 
mPASI Score – Summary by Visit on the FAS, Averaged Multiple Imputations, 
Hypothetical Strategy 
Table 14.2.1.4 
mPASI Score – Summary by Visit on the PPS, Observed Cases 
Table 14.2.1.5 
%Change in mPASI Score at Week 8 – Primary Analysis on the FAS using MI, Treatment-
policy Strategy 


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Table 14.2.1.6 
%Change in mPASI Score at Week 8 – Tipping-point Sensitivity Analysis on the FAS using 
MI, Treatment-policy Strategy 
Table 14.2.1.7 
%Change in mPASI Score at Week 8 – Sensitivity Analysis on the FAS using MI, 
Hypothetical Strategy 
Table 14.2.1.8 
%Change in mPASI Score at Week 8 – Sensitivity Analysis on the PPS, Treatment-policy 
Strategy 
14.2.2 
Secondary Efficacy Endpoints 
Table 14.2.2.1 
PGA on the Body and PGA Success Rate on the Body – Summary by Visit on the FAS, 
Observed Cases 
Table 14.2.2.2 
PGA Success Rate on the Body – Summary by Visit on the FAS, Averaged Multiple 
Imputations, Treatment-policy Strategy 
Table 14.2.2.3 
PGA Success Rate on the Body – Summary by Visit on the FAS, Non-responder 
Imputations, Treatment-policy Strategy 
Table 14.2.2.4 
PGA Success Rate on the Body – Summary by Visit on the FAS, Averaged Multiple 
Imputations, Hypothetical Strategy 
Table 14.2.2.5 
PGA Success Rate on the Body at Week 8 – Primary Analysis on the FAS using MI, 
Treatment-policy Strategy 
Table 14.2.2.6 
PGA Success Rate on the Body at Week 8 – Sensitivity Analysis on the FAS using NRI, 
Treatment-policy Strategy 
Table 14.2.2.7 
PGA Success Rate on the Body at Week 8 – Sensitivity Analysis on the FAS using MI, 
Hypothetical Strategy 
Table 14.2.2.8 
PTCS – Summary by Visit on the FAS, Observed Cases 
Table 14.2.2.9 
PTCS – Summary by Visit on the FAS, LOCF Imputations, While-on-treatment Strategy 
Table 14.2.2.10 
PTCS – Summary by Visit on the PPS, LOCF Imputations, While-on-treatment Strategy 
Table 14.2.2.11 
PTCS Total Score at Week 8 – Primary Analysis on the FAS using LOCF, While-on-
treatment Strategy 
Table 14.2.2.12 
PTCS Total Score at Week 8 – Sensitivity Analysis on the PPS using LOCF, While-on-
treatment Strategy 
Table 14.2.2.13 
mPASI 75 at Week 8 – Analysis on the FAS using MI, Treatment-policy Strategy 
Table 14.2.2.14 
PGA on the Scalp and PGA Success Rate on the Scalp – Summary by Visit on the FAS, 
Observed Cases 
Table 14.2.2.15 
PGA Success Rate on the Scalp – Summary by Visit on the FAS, Averaged Multiple 
Imputations, Treatment-policy Strategy 
Table 14.2.2.16 
PGA Success Rate on the Scalp – Summary by Visit on the FAS, Non-responder 
Imputations, Treatment-policy Strategy 
Table 14.2.2.17 
PGA Success Rate on the Scalp – Summary by Visit on the FAS, Averaged Multiple 
Imputations, Hypothetical Strategy 
Table 14.2.2.18 
PGA Success Rate on the Scalp at Week 8 – Primary Analysis on the FAS using MI, 
Treatment-policy Strategy 
Table 14.2.2.19 
PGA Success Rate on the Scalp at Week 8 – Sensitivity Analysis on the FAS using NRI, 
Treatment-policy Strategy 
Table 14.2.2.20 
PGA Success Rate on the Scalp at Week 8 – Sensitivity Analysis on the FAS using MI, 
Hypothetical Strategy 
14.2.3 
Other Efficacy Endpoints and Subject-Reported Outcomes 
Table 14.2.3.1 
%Change in mPASI Score at Week 4 – Analysis on the FAS using MI, Treatment-policy 
Strategy 
Table 14.2.3.2 
mPASI 75 at Week 4 – Analysis on the FAS using MI, Treatment-policy Strategy 
Table 14.2.3.3 
SGA – Summary by Visit on the FAS, Observed Cases 
Table 14.2.3.4 
PTCS Total Score at Week 4 –Analysis on the FAS using LOCF, While-on-treatment 
Strategy 
Table 14.2.3.5 
DLQI – Summary by Visit on the FAS, Observed Cases 


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Table 14.2.3.6 
DLQI Score – Summary by Visit on the FAS, Averaged Multiple Imputations, Treatment-
policy Strategy 
Table 14.2.3.7 
DLQI Score at Week 4 and Week 8 – Analysis on the FAS using MI, Treatment-policy 
Strategy 
Table 14.2.3.8 
EQ-5D – Summary by Visit on the FAS, Observed Cases 
Table 14.2.3.9 
EQ-VAS at Week 4 and Week 8 – Analysis on the FAS using MI, Treatment-policy 
Strategy 
Table 14.2.3.10 
BSA Involvementon the Body and the Scalp – Summary by Visit on the FAS, Observed 
Cases 
14.3 
Safety Data 
14.3.1 
Adverse Events 
Table 14.3.1.1 
Adverse Events – Overview on the Safety Set 
Table 14.3.1.2 
Treatment-emergent Adverse Events – Summary by SOC and PT on the Safety Set 
Table 14.3.1.3 
Treatment-emergent Adverse Events – Summary by Maximum Severity, SOC and PT on the 
Safety Set 
Table 14.3.1.4 
Treatment-emergent Drug-related Adverse Events – Summary by SOC and PT on the Safety 
Set 
Table 14.3.1.5 
Treatment-emergent Drug-related Adverse Events – Summary by Maximum Severity, SOC 
and PT on the Safety Set 
Table 14.3.1.6 
Treatment-emergent Serious Adverse Events – Summary by SOC and PT on the Safety Set 
Table 14.3.1.7 
Treatment-emergent Drug-related Serious Adverse Events – Summary by SOC and PT on 
the Safety Set 
Table 14.3.1.8 
Treatment-emergent Adverse Events Leading to Drug Withdrawal – Summary by SOC and 
PT on the Safety Set 
Table 14.3.1.9 
Treatment-emergent Drug-related Adverse Events Located in the Treatment Area – 
Summary by SOC and PT on the Safety Set 
14.3.2 
Local Skin Reaction 
Table 14.3.2.1 
Local Skin Reaction Assessments – Summary by Visit on the Safety Set 
Table 14.3.2.2 
Most Intense Local Skin Reaction Assessments – Summary on the Safety Set 
14.3.3 
Laboratory Parameters 
Table 14.3.3.1.1 
Serum Biochemistry – Summary by Visit on the Safety Set 
Table 14.3.3.1.2 
Serum Biochemistry – Shifts from Baseline by Visit on the Safety Set 
Table 14.3.3.2.1 
Urinalysis – Summary by Visit on the Safety Set 
Table 14.3.3.2.2 
Urinalysis – Shifts from Baseline by Visit on the Safety Set 
Table 14.3.3.3 
Urine Pregnancy Tests – Summary by Visit on the Safety Set 
14.3.4 
Vital Signs 
Table 14.3.4 
Vital Signs - Summary by Visit on the Safety Set 
14.3.5 
Physical Examination 
Table 14.3.5 
Physical and Dermatological Examination – Summary by Visit on the Safety Set 
 
7.4 
Post-text Figures 
The following post-text figures will be produced. 
 
 


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Table 7: Table of Content of Post-Text Figures 
Figure 14.2.1.1 
Percentage Change from Baseline in mPASI – Box Plot by Treatment and Visit, Treatment 
Policy Strategy, FAS Using MI 
Figure 14.2.1.2 
Percentage Change from Baseline in mPASI – Box Plot by Treatment and Visit, Treatment 
Policy Strategy, PPS 
Figure 14.2.2.1 
PGA Success Rate on the Body – Bar Chart by Treatment and Visit, Treatment Policy 
Strategy, FAS Using MI 
Figure 14.2.3.1 
PTCS Total Score - Box Plot by Treatment and Visit, While on Treatment Strategy, FAS 
Using LOCF 
 
7.5 
Statistical Output Documentation 
Original SAS® outputs of inferential statistical procedures will be available upon request. 
7.6 
Data Listings 
The following individual patient data listings will be produced. 
Table 8: Table of Content of Data Listings 
16.1 
 
Listing 16.1.7 
Subject Enrollment and Randomization 
16.2 
Patient Data Listings 
16.2.1 
End of Study 
Listing 16.2.1.1 
Screen Failure 
Listing 16.2.1.2 
Subject Disposition 
Listing 16.2.1.3 
Follow-up Visit 
16.2.2 
Protocol Deviations 
Listing 16.2.2.1 
Protocol Deviations 
16.2.3 
Analysis Populations 
Listing 16.2.3.1 
Analyses Populations 
16.2.4 
Baseline Characteristics 
16.2.4.1 
Demographics  
Listing 16.2.4.1.1 
Demographic Data, Height and Weight 
16.2.4.2 
Diagnosis 
Listing 16.2.4.2.1 
Details of Diagnosis and Psoriasis Treatment History 
16.2.4.3 
Prior and Concomitant Therapy 
Listing 16.2.4.3.1 
Prior and Concomitant Therapy – Details 
Listing 16.2.4.3.2 
Prior and Concomitant Therapy – Coding 
16.2.4.4 
Prior and Concomitant Procedures 
Listing 16.2.4.4.1 
Concomitant Procedures - Details 
Listing 16.2.4.4.2 
Concomitant Procedures - Coding 
16.2.4.5 
Medical History 
Listing 16.2.4.5.1 
Medical History - Details 
Listing 16.2.4.5.2 
Medical History - Coding 
16.2.5 
Other Collected Data 
Listing 16.2.5.1 
Inclusion Criteria 


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Listing 16.2.5.2 
Exclusion Criteria 
Listing 16.2.5.3 
Dates of Visits and Times Between Visits 
Listing 16.2.5.4 
End of Treatment 
Listing 16.2.5.5 
Study Drug Assignment per Visit 
Listing 16.2.5.6 
Study Drug Return Weight per Visit 
Listing 16.2.5.7 
Study Drug Accountability per Visit 
Listing 16.2.5.8 
Subject Treatment Diary Card & Dose Documentation 
Listing 16.2.5.9 
Overall Study Drug Exposure and Compliance 
Listing 16.2.5.10 
General Comments 
16.2.6 
Individual Efficacy Data 
Listing 16.2.6.1.1 
mPASI Score by Visit 
Listing 16.2.6.1.2 
mPASI Assessments by Visit 
Listing 16.2.6.2.1 
PGA on the Body by Visit 
Listing 16.2.6.2.2 
PGA on the Scalp by Visit 
Listing 16.2.6.3 
PTCS by Visit 
Listing 16.2.6.4 
SGA by Visit 
Listing 16.2.6.5 
DLQI by Visit 
Listing 16.2.6.6 
EQ-5D by Visit 
Listing 16.2.6.7 
BSA Involvement Assessment by Visit 
16.2.7 
Safety & Tolerability Listings 
16.2.7.1 
Adverse Events Listings 
Listing 16.2.7.1.1 
Adverse Events - Timing 
Listing 16.2.7.1.2 
Adverse Events – Details 
Listing 16.2.7.1.3 
Adverse Events – Coding 
Listing 16.2.7.1.4 
Serious Adverse Events - Timing 
Listing 16.2.7.1.5 
Serious Adverse Events – Details 
Listing 16.2.7.1.6 
Serious Adverse Events – Coding 
Listing 16.2.7.1.7 
Adverse Events Leading to Drug Withdrawal - Timing 
Listing 16.2.7.1.8 
Adverse Events Leading to Drug Withdrawal – Details 
Listing 16.2.7.1.9 
Adverse Events Leading to Drug Withdrawal – Coding 
16.2.7.2 
Local Skin Reactions 
Listing 16.2.7.2 
Local Skin Reactions Assessment by Visit 
16.2.7.3 
Laboratory Parameters 
Listing 16.2.7.3.1 
Serum Biochemistry by Visit 
Listing 16.2.7.3.2 
Urinalysis by Visit 
Listing 16.2.7.3.3 
Urine Pregnancy Test by Visit 
16.2.7.4 
Vital Signs 
Listing 16.2.7.4 
Vital Signs by Visit 
16.2.7.5 
Physical Examination 
Listing 16.2.7.5 
Physical and Dermatological Examination by Visit