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
Phase: PHASE3
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
 27 February 2018 
 
 
 
 
 
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 MC2-01 Cream Vehicle and Active Comparator 
in Subjects with Mild-to-Moderate Psoriasis Vulgaris 
 
Investigational product: 
MC2-01 (calcipotriene/betamethasone dipropionate, w/w 
0.005%/0.064%) cream 
Active Comparator: 
Calcipotriene/betamethasone (calcipotriene/betamethasone 
dipropionate, w/w 0.005%/0.064%) gel/topical suspension  
 
Protocol No: 
MC2-01-C2 
 
IND No: 
127152 
 
Development phase: 
3 
 
Document status: 
Final 
 
Document version: 
Version 3.0 
 
Document date: 
27 February 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. 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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CLINICAL TRIAL PROTOCOL APPROVAL 
Product: MC2-01 (calcipotriene/betamethasone dipropionate) Cream 
Protocol number: MC2-01-C2 
Protocol title: 
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  
 
The following persons have approved this clinical trial protocol, which are separate document 
adjoined to this document: 
 
Johan Selmer, MD, VP Medical Affairs, MC2 Therapeutics                                 
 
Carol Udell, Senior Director, Clinical Data Management and Biostatistics, Novella 
 
 
Linda Stein Gold, MD, International Coordinating Investigator, Henry Ford Medical Center                  
 
 
 
 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
- 3 - 
SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
Product: 
MC2-01 (calcipotriene/betamethasone dipropionate) Cream 
Protocol number: MC2-01-C2 
Protocol Version: 3.0 
Protocol title: 
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  
 
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, 
clinically and administratively, 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 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF TABLES .........................................................................................................................7 
LIST OF FIGURES .......................................................................................................................8 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...............................................9 
1.0 
SYNOPSIS ..........................................................................................................................11 
Primary Endpoint ........................................................................................................12 
Secondary Endpoints ..................................................................................................13 
2.0 
INTRODUCTION ..............................................................................................................19 
2.1 
Background ...................................................................................................19 
2.2 
Rationale of the Trial ....................................................................................20 
2.3 
Benefit-risk Assessment................................................................................20 
3.0 
TRIAL OBJECTIVES AND PURPOSE ..........................................................................21 
4.0 
TRIAL DESIGN .................................................................................................................21 
4.1 
Overall Trial Design .....................................................................................21 
4.2 
Trial Endpoints..............................................................................................22 
4.2.1 
Primary Endpoint .........................................................................................22 
4.2.2 
Secondary Endpoints ....................................................................................23 
4.2.3 
Safety Endpoints ..........................................................................................23 
4.2.4 
Other Endpoints ............................................................................................23 
5.0 
SELECTION OF TRIAL POPULATION .......................................................................24 
5.1 
Subject Population ........................................................................................24 
5.2 
Inclusion Criteria ..........................................................................................24 
5.3 
Exclusion Criteria .........................................................................................24 
5.4 
Discontinuation of Treatment .......................................................................26 
5.5 
Replacement Policy ......................................................................................26 
6.0 
TRIAL TREATMENTS ....................................................................................................27 
6.1 
Investigational Product .................................................................................27 
6.2 
Active Comparator Product ..........................................................................27 
6.3 
Dosing Regimen............................................................................................27 
6.4 
Dose Modification ........................................................................................27 
6.5 
Packaging, Labeling, and Storage .................................................................28 
6.6 
Assignment to Treatment ..............................................................................28 

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Clinical Trial Protocol 
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27 February 2018 
 
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6.6.1 
Randomisation ..............................................................................................28 
6.6.2 
Blinding ........................................................................................................28 
6.7 
Prior, Concomitant, and Prohibited Therapy ................................................29 
6.7.1 
Washout of Prohibited Medications Prior to Enrollment .............................29 
6.7.2 
Prohibited Medications During the Trial .....................................................29 
6.7.3 
Allowed Treatment on the Face, Scalp, Skin Folds and Genital Skin 
Only ..............................................................................................................29 
6.8 
Treatment Compliance ..................................................................................30 
7.0 
VISIT SCHEDULE AND ASSESSMENTS .....................................................................30 
7.1 
Trial Procedures ............................................................................................30 
7.2 
Trial Visits and Assessments ........................................................................30 
7.2.1 
Visit 0/Screening (Day –30 to Day 0) ..........................................................30 
7.2.2 
Visit 1/Baseline (Day 0) ...............................................................................31 
7.2.3 
Visit 2/ Week 1 (Day 7 ±2) ..........................................................................32 
7.2.4 
Telephone Call (TC)/Visit 3/Week 2 (Day 14 ±2) .......................................32 
7.2.5 
Visit 4/Week 4 (/Day 28 ±2) ........................................................................32 
7.2.6 
Visit 5/Week 6 (Day 42 ±2) .........................................................................33 
7.2.7 
Visit 6/Week 8 (End of Treatment) (Day 56 ±2) .........................................34 
7.2.8 
Visit 7/Week 10 (Follow Up /End of Trial) (Day 70 ±2 days) ....................34 
7.2.9 
Early Termination ........................................................................................35 
7.2.10 
Unscheduled Visit and Telephone Calls ......................................................36 
7.3 
Investigator Assessments ..............................................................................36 
7.3.1 
Physician’s Global Assessment ....................................................................36 
7.3.2 
Extent and Severity of Redness, Thickness, and Scaliness ..........................37 
7.3.3 
Body Surface Area Involvement of Psoriasis Vulgaris ................................38 
7.3.4 
Local Skin Reactions ....................................................................................38 
7.4 
Patient Reported Outcomes (PROs)..............................................................40 
7.4.1 
Subject Global Assessment of disease severity (SGA) ................................41 
7.4.2 
Dermatology Life Quality Index (DLQI) .....................................................41 
7.4.3 
EuroQOL five dimensions questionnaire (EQ-5D) ......................................41 
7.4.4 
The Psoriasis Treatment Convenience Scale ...............................................41 
7.4.5 
Itch by Numerical Rating Scale (Itch by NRS) ............................................41 
7.5 
Assessment of Pharmacokinetics (not applicable) ........................................42 
7.6 
Assessment of Safety ....................................................................................42 

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Clinical Trial Protocol 
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27 February 2018 
 
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7.6.1 
Adverse Events .............................................................................................42 
7.6.1.1 
Adverse Events Assessments ...........................................................42 
7.6.1.2 
Timing .............................................................................................42 
7.6.1.3 
Severity of Adverse Events ..............................................................43 
7.6.1.4 
Relationship of an Adverse Event to Trial Treatment .....................43 
7.6.1.5 
Unexpected Adverse Events ............................................................43 
7.6.1.6 
Trial Medication Overdose .............................................................44 
7.6.1.7 
Pregnancy .......................................................................................44 
7.6.2 
Serious Adverse Event .................................................................................44 
7.6.3 
Safety Laboratory Assessments ...................................................................45 
7.6.4 
Pregnancy Testing ........................................................................................46 
7.6.5 
Vital Signs ....................................................................................................46 
7.6.6 
Physical Examination ...................................................................................46 
7.6.7 
Electrocardiogram ........................................................................................47 
7.7 
Appropriateness of Measurements ................................................................47 
8.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
STATISTICAL AND ANALYTICAL PLANS ...............................................................48 
8.1 
General Considerations for Data Analysis ....................................................48 
8.2 
Sample Size and Power Considerations ........................................................48 
8.3 
Analysis Populations .....................................................................................50 
8.4 
Handling of Missing Data .............................................................................51 
8.5 
Analysis of Efficacy ......................................................................................51 
8.5.1 
Primary Efficacy Endpoint(s) .......................................................................51 
8.5.1.1 
Analysis of the primary endpoint ....................................................51 
8.5.1.2 
Sensitivity Analyses .........................................................................52 
8.5.2 
Secondary Efficacy Endpoints .....................................................................52 
8.5.3 
Other Endpoints ............................................................................................55 
8.6 
Analysis of Safety .........................................................................................56 
8.6.1 
Adverse Events .............................................................................................56 
8.6.2 
Local Skin Reaction Assessment .................................................................56 
8.6.3 
Other safety variables ...................................................................................56 
9.0 
CHANGES IN THE PLANNED TRIAL .........................................................................57 
9.1 
Protocol Amendments ...................................................................................57 
9.2 
Termination or Suspension of the Trial ........................................................57 
10.0 DATA HANDLING AND RECORD KEEPING ............................................................57 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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10.1 
Recording of Data .........................................................................................57 
10.1.1 
Source Documents ........................................................................................57 
10.1.2 
Case Report Forms .......................................................................................58 
10.2 
Retention of Documents ...............................................................................58 
11.0 QUALITY CONTROL AND QUALITY ASSURANCE ...............................................58 
11.1 
Direct Access to Source Documents .............................................................58 
11.2 
Monitoring Procedures..................................................................................59 
11.3 
Audit and Inspection .....................................................................................59 
12.0 ETHICS ...............................................................................................................................59 
12.1 
Ethical Conduct of the Trial ..........................................................................59 
12.2 
Institutional Review Board (IRB) or Independent Ethics Committee 
(IEC) .............................................................................................................59 
12.3 
Subject Information and Consent..................................................................59 
12.4 
Disclosure and Confidentiality .....................................................................60 
12.5 
Confidentiality of Trial Documentation........................................................60 
12.6 
Privacy of Individual Health Information .....................................................60 
13.0 EMERGENCY PROCEDURES .......................................................................................60 
13.1 
Emergency Un-blinding ................................................................................60 
13.2 
Reporting of Serious Adverse Events and Pregnancies ................................61 
13.2.1 
Contact Person(s) and Number(s) ................................................................61 
13.2.2 
Reporting Procedures ...................................................................................61 
14.0 INSURANCE ......................................................................................................................61 
15.0 PUBLICATION POLICY .................................................................................................61 
16.0 REFERENCE LIST ...........................................................................................................62 
17.0 APPENDICES ....................................................................................................................65 
Appendix 1: Contact List of MC2, Protocol Authors, Vendors, and International 
Coordinating Investigator .............................................................................65 
Appendix 2: Vendors .........................................................................................................66 
 
LIST OF TABLES 
Table 1-1 Visit Schedule and Assessments .................................................................................17 
Table 7-1 Physician’s Global Assessment (PGA) ......................................................................37 
Table 7-2 Local Skin Reaction Scores ........................................................................................40 
Table 7-3 Fitzpatrick Skin Type Classification ..........................................................................47 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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LIST OF FIGURES 
Figure 4-1  Trial Design ................................................................................................................22 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
Abbreviation 
Definition 
ACE 
Angiotensin converting enzyme 
AE 
Adverse event 
ANOVA 
Analysis of variance 
AUC 
Area under the curve 
BDP 
Betamethasone dipropionate 
BOCF 
Baseline observation carried forward 
BSA 
Body surface area 
CAL 
Calcipotriene 
CI 
Confidence interval 
CRO 
Contract Research Organisation 
DLQI 
Dermatology Life Quality Index  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EQ-5D 
EuroQOL five dimensions questionnaire 
EQ-VAS 
EQ-5D visual analog scale 
EU 
European Union 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IP 
Investigational product 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
IWR 
Interactive web response 
LOCF 
Last observation carried forward 
MCMC 
Markov Chain Monte Carlo 
MI 
Multiple imputation  
mPASI 
Modified Psoriasis Area and Severity Index 
MedDRA 
Medical Dictionary for Regulatory Activities 
NI 
Non-inferiority 
NRI 
Non-responder imputation 
NRS 
Numerical Rating Scale 
OTC 
Over the counter 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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Abbreviation 
Definition 
PASI 
Psoriasis Area and Severity Index 
PASI 75 
75% reduction in mPASI 
PASI 50 
50% reduction in mPASI 
PGA 
Physician’s global assessment 
PP 
Per protocol 
PRO 
Patient-reported outcome 
PUVA 
Psoralen + ultraviolet-A radiation 
QOL 
Quality of Life 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SGA 
Subject’s global assessment 
SUSAR 
Suspected unexpected serious adverse reaction 
TC 
Telephone call 
UBC 
United BioSource Corporation 
UPT 
Urine pregnancy test 
US  
United States 
UVB 
Ultraviolet B 
VAS 
Visual analog scale 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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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 MC2-01 
Cream Vehicle and Active Comparator in Subjects with Mild-to-Moderate 
Psoriasis Vulgaris 
Protocol Number: 
MC2-01-C2 
Sponsor:  
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
Development Phase: 
3 
Trial Objectives: 
The primary objective is to show therapeutic non-inferiority of MC2-01 cream 
to active comparator, as well as 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 4-week 
screening period, an 8-week treatment period, and a 2-week post-treatment 
follow-up period.   
Planned Sample Size: 
A total enrolment of approximately 791 subjects is planned in order to have 
approximately 712 completed subjects.  
Under the assumptions of the trial, a sample size of N=305 per active treatment 
group is calculated to satisfy the non-inferiority conditions with 90% power. 
Assuming 90% completion rate of the randomised subjects, a total sample size 
of N=339 per active treatment group is required to be randomised. Following a 
3:1:3 randomisation ratio, 113 subjects will be randomised to receive the  
MC2-01 cream vehicle. 
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 Physician Global Assessment (PGA) of disease severity of mild or moderate 
on the body (trunk and/or limbs) and a minimum modified Psoriasis Area and 
Severity Index (mPASI) score of at least 2. 
Investigational Product (IP): 
MC2-01 cream (calcipotriene (CAL) and betamethasone dipropionate (BPD), 
w/w 0.005%/0.064%). 
MC2-01 cream vehicle. 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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Reference/Control Product(s): 
Calcipotriene/betamethasone dipropionate gel/topical suspension, w/w 
0.005%/0.064%, approved in the United States (US) as Taclonex® topical 
suspension and in the European Union (EU) as Dovobet®/Daivobet® gel.  
Efficacy Evaluation Criteria: 
Efficacy will be assessed by the investigator (PGA and mPASI), and by subject’s 
global assessments (SGA) of disease severity, Dermatology Life Quality Index 
(DLQI) questionnaire, and EuroQOL five dimensions (EQ-5D) questionnaire. 
Safety Evaluation Criteria: 
Adverse event (AE) incidence and severity, laboratory test results (serum 
biochemistry, urinalysis, pregnancy testing for female subjects of childbearing 
potential), Electrocardiogram (ECG), vital signs assessments, physical 
examination. 
Statistical Methods: 
Primary Endpoint  
The primary efficacy endpoint is the proportion of subjects in each treatment 
group with ‘treatment success’ at Week 8, defined as a minimum 2-point 
decrease from Baseline to Week 8 in PGA score; i.e., a score of 0 (clear) or 1 
(almost clear) disease for subjects with moderate disease at Baseline; or a score 
of 0 (absent) for subjects with mild disease at Baseline.  
Non-inferiority Evaluation 
The PGA response rate for MC2-01 cream and for active comparator at Week 8 
will first be compared with that for MC2-01 cream vehicle at Week 8 for a 
superiority evaluation, based on the Intent to Treat (ITT) Population, using a 
LOGISTIC model with treatment, baseline value of PGA and study site as 
independent variables. Missing data will be imputed using multiple imputations 
(MI). 
If and only if superiority to vehicle for both MC2-01 cream and for active 
comparator can be claimed at the 5% significance level, the non-inferiority (NI) 
analysis of the primary endpoint will then be conducted based on the PP 
Population. The PGA success rate of MC2-01 cream at Week 8 will be compared 
with that of active comparator at Week 8, using a non-inferiority margin of 10% 
points.  
The percentage of subjects in each group with treatment response will be 
calculated along with its 95% confidence interval (CI) using normal 
approximation. A 95%, 2-sided CI on the difference between MC2-01 cream and 
active comparator will be computed using normal approximation. MC2-01 will 
be considered non-inferior to Active Comparator if the lower bound of the 2-
sided 95% CI is ≥ -10% points. 
Sensitivity Analyses 
As sensitivity analyses, the analyses of superiority will also be made based on 
the ITT population using other imputation methods than MI (last observation 
carried forward (LOCF), baseline observation carried forward (BOCF), non-

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Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
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responder imputation (NRI)). Further an analysis based on the Per Protocol (PP) 
population and using complete case analysis with no imputation of missing data 
will be made. 
The non-inferiority analysis of the primary endpoint will also be performed 
based on the ITT population using a variety of imputation methods as sensitivity 
analyses (MI, LOCF, BOCF, NRI) 
For the sensitivity non-inferiority analysis using MI, the treatment difference 
will be evaluated for each of the multiple imputed datasets using PROC FREQ 
with RISKDIFF option. The estimates and standard errors of the response rate 
difference based on the imputed datasets will be combined by applying Rubin’s 
rules in PROC MIANALYZE and the 95% CI of the difference will be 
computed. 
Secondary Endpoints 
Secondary endpoints are the following 
• 
Percentage change from Baseline in the mPASI score at Week 8;  
o 
Superiority evaluation: The percentage change will be compared 
between MC2-01 cream vs. vehicle and active comparator vs. 
vehicle for superiority using an analysis of covariance (ANCOVA) 
model with treatment, baseline PGA severity (mild/moderate), 
baseline mPASI and study site as independent variables. The 
analysis will be based on the ITT population using multiple 
imputation. 
o 
Non-inferiority evaluation: The percentage change will be 
compared between MC2-01 cream and active comparator using a 
similar model as for the evaluation of superiority. Non-inferiority 
will be claimed if the lower limit of the relevant two-sided CI (see 
derivation of alpha level below), derived from the difference in 
LSMEANS, will be ≥ -10%. The analysis will be based on the PP 
population with no imputation of missing data. 
• 
Subject assessment of treatment convenience at Week 8 using a Psoriasis 
Treatment Convenience Scale (PCTS)  
o 
Superiority evaluation: PCTS will be compared for superiority 
between MC2-01 cream and active comparator using an ANOVA 
model with treatment and trial site as independent variables; 
superiority will be claimed if the lower limit of the relevant two-
sided CI (see derivation of alpha level below), derived from the 
difference in LSMEANS, will be >0. The analysis will be based 
on the ITT population.  Missing and invalid PTCS scores will be 
imputed using the last valid measure prior to the visit. 

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Clinical Trial Protocol 
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• 
Change in itch intensity assessed on a numerical rating scale (Itch by NRS) 
from baseline to Week 4: 
o 
 Superiority evaluation. (MC2-01 cream vs MC2-01 cream 
vehicle). Superiority between MC2-01 cream and vehicle will be 
assessed by using an ANCOVA model with treatment, baseline 
PGA severity (mild/moderate), baseline Itch by NRS value and 
analysis site as independent variables. The primary analysis will be 
based on the ITT population, using multiple imputations 
• 
Percentage of subjects with four-point improvement on the numerical 
rating scale (Itch by NRS) from baseline to Week 4 
o 
Superiority evaluation (MC2-01 cream vs MC2-01 cream 
vehicle). The analysis is made on the subgroup of subjects from 
the ITT populations with Itch (assessed by NRS) ≥ 4 at baseline. 
Superiority between MC2-01 cream and vehicle will be assessed 
by using a logistic model with treatment, baseline PGA severity 
(mild/moderate), baseline Itch by NRS value and analysis site as 
independent variables. Missing data will be imputed using 
multiple imputations. 
The global Type-I error will be controlled by the following testing procedure: 
1. 
Secondary endpoints will be tested only if the primary endpoint will reject 
the Null-hypothesis; 
2. 
The two secondary endpoints ‘Percentage reduction from Baseline in the 
mPASI score at Week 8, and Subject assessment of treatment convenience 
at Week 8 using a Psoriasis Treatment Convenience Scale will be tested 
in with a loopback procedure with initial error probability weights 2/3 for 
H1 (mPASI) and 1/3 for H2 (subject assessment of treatment 
convenience), resulting in α1=0.0333 and α2=0. 0167. If any of the Null-
hypotheses can be rejected, the respective error probability will be 
shuffled to the other hypothesis 
3. 
If and only if both non-inferiority of MC2-01 to active comparator with 
respect to Percentage reduction from Baseline in mPASI as well as 
superiority of MC2-01 vs. active comparator with respect to Psoriasis 
treatment convenience scale has been demonstrated, superiority of MC2-
01 vs vehicle with respect to the below endpoints will be tested in a 
hierarchical manner: 
• 
Change in itch intensity assessed on a numerical rating scale (Itch by 
NRS) from baseline to Week 4 

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• 
Percentage of subjects with four-point improvement on the numerical 
rating scale (Itch by NRS) from baseline to Week 4 (In the subgroup 
of subjects with an NRS score ≥ 4 at baseline) 
All secondary endpoints will be described using summary statistics. For mPASI 
and NRS, absolute values, absolute reduction, and percentage reduction from 
baseline will be summarized using mean, median, SD, quartiles and ranges for 
each treatment group by visit. Frequency counts and percentages of NRS 4-point 
improvement responders will be provided for each treatment group by visit. For 
PTCS score, absolute values will be summarized using descriptive statistics for 
each treatment group by visit. 
Other Endpoints 
Efficacy 
• 
PGA success rate at Week 4; 
• 
Percentage change from Baseline in the mPASI score at Week 4; 
• 
Number of subjects with PASI 50 (at least 50% reduction in mPASI from 
Baseline) at Week 4 and Week 8;  
• 
Number of subjects with PASI 75 (at least 75% reduction in mPASI from 
Baseline) at Week 4 and Week 8; 
• 
Change from Baseline in SGA at Week 4 and Week 8.  
Patient reported outcomes (PRO)  
• 
Change in DLQI score at Week 4 and Week 8; The DLQI will be scored 
according to the developer instructions. Missing values, if any, will be 
incorporated based on the developers scoring instructions. The DLQI will 
also be summarised by the following domains: symptoms and feelings, 
daily activities, leisure, work and school, personal relationships, and 
treatment. 
• 
Change in EQ-5D score at Week 4 and Week 8. The EQ-5D will be 
scored according to the developer instructions. 
• 
Change in itch intensity assessed on a numerical rating scale (Itch by 
NRS) from baseline to Week 1 as well as Week 8 (MC2-01 cream vs 
MC2-01 cream vehicle). 

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Other efficacy endpoints (PASI 50 and PASI 75) will be analysed following 
the same method as described for the primary efficacy analysis, except that no 
formal non-inferiority test will be conducted.  
Change from Baseline in SGA at Week 4 and Week 8 will be analysed using 
an ANCOVA model with treatment, baseline PGA severity (mild/moderate) 
baseline SGA and study site as independent variable. The subject convenience 
data will be summarised using summary statistics for each treatment group. 
The Patient reported outcomes DLQI, EQ-5D, and Itch by NRS will be 
analysed using an ANCOVA model with treatment, baseline PGA severity 
(mild/moderate), analysis site and respective baseline patient reported 
outcome as independent variables. 
Safety: The assessment of safety will be based mainly on the frequency of AEs 
and on the number of laboratory values that fall outside of predetermined ranges. 
AEs will be presented in data listings and summarised by frequency and severity 
for each treatment group. Laboratory and vital sign data will be presented in data 
listings. Abnormal laboratory findings will be presented. 
Trial Sites: 
Approximately 57 trial sites in the US 
Planned Dates of Trial: 
2nd quarter, 2017 

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Table 1-1 
Visit Schedule and Assessments 
Visit 
Screening/ 
Visit 0a) 
Visit 1 
Visit 
2 
TC 
(Visit 
3)  
Visit 
4 
Visit 
5 
Visit 
6 
/ETb) 
FollowUp, 
Visit 7 
ETc) 
 
 
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 Consent d) 
X 
X 
 
 
 
 
 
 
Inclusion/Exclusion 
Criteria 
[X] 
X 
 
 
 
 
 
 
Demographics, medical 
history 
[X] 
X 
 
 
 
 
 
 
Concomitant medication 
[X] 
X 
X 
 
X 
X 
X 
X 
Concurrent diagnoses 
[X] 
X 
 
 
 
 
 
 
Physical Exam  
[X] 
X 
 
 
X 
 
X 
 
Vital signs  
 
X 
 
 
X 
 
X 
 
Pregnancy Test e) 
[X] 
X 
 
 
X 
 
X 
 
Biochemistry/Urinalysis  
 
Xf) 
 
 
Xf) 
 
Xf) g) 
Xf) g) 
ECG 
 
Xf) 
 
 
Xf) 
 
Xf) 
 
Randomisation 
 
X 
 
 
 
 
 
 
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 
 
Itch by NRS 
 
X 
X 
 
X 
 
X 
 
PGA scoring 
[X] 
X 
X 
 
X 
X 
X 
 
mPASI scoring 
[X] 
X 
X 
 
X 
X 
X 
 
Body Surface Area (BSA) 
involvement 
[X] 
X 
 
 
X 
 
X 
 
Dispensing of IP 
 
X 
X 
 
X 
X 
 
 
Return of IP 
 
 
X 
 
X 
X 
X 
 
Compliance 
 
 
X 
X 
X 
X 
X 
 
Local skin reactions 
 
X 
X 
 
X 
X 
X 
X 
AE(s) h) 
 
X 
X 
X 
X 
X 
X i) 
X i) 
Return all trial materials 
 
 
 
 
 
 
X 
X 
 
 

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TC = telephone call; ET = early termination; ECG = electrocardiogram; PGA = physician’s 
global assessment; mPASI = modified Psoriasis Area and Severity Index; SGA = subject’s 
global assessment; DLQI= Dermatology Life Quality Index; EQ-5D = EuroQOL five dimensions 
questionnaire, Itch by NRS; Itch by Numerical Rating Scale, IP = investigational product; AE = 
adverse event. 
 
a) A washout period of up to 4 weeks 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. 
b) Procedures for subjects who withdraw from the study before Visit 6/Week 8. 
c) Procedures for subjects who withdraw from the study after Visit 6/Week 8 but before  
Visit 7/Week 10 
d) Informed consent must be signed both by subject and investigator or designee 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. 
f) If a laboratory or ECG result is abnormal and judged as clinical significant, the investigator 
or designee must follow-up as clinically appropriate (this may involve requesting repeat 
samples). 
g) If albumin-corrected serum calcium is above the reference range at the last on-treatment 
visit, a follow-up test at ET must be performed. 
h) AEs are to be collected from the date of signing informed consent, i.e., during the washout 
period. 
i) Monitor AEs that are considered related to the trial product until they are resolved or until 
the medical condition of the subject is stable.  
 
 
 
 

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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%1 whereas the 
prevalence in Europe varies anywhere from 0.6 to 6.5%2 with an average of approximately 3%3. 
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 cases4. 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 umbilicus5. Patients with psoriasis have 
reduced quality of life with reduced levels of employment and income6, 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 depression7,8. 
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 diseases9,10 . 
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 calcipotriene (CAL) 
and betamethasone dipropionate (BDP) is superior to each of the single agent11-13.There is strong 
scientific rationale for the combination of vitamin D and glucocorticosteroids both with respect 
to efficacy and safety14-16, and combination treatment with a Vitamin D analog and a topical 
corticosteroid is recommended in both American and European guidelines17-20. 
Calcipotriene and betamethasone 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 the marketed product CAL/BDP 
combination gel/topical suspension, which is marketed under the brand name Taclonex® Topical 
Suspension in US and Daivobet®Gel or Dovobet® Gel in the rest of the world. This product is a 
liquid oil that contains the active ingredients CAL/BDP (w/w 0.005%/0.064%) in the same 
concentrations as MC2-01 cream. 
The cosmetic qualities of a topical product is of importance for patient adherence to treatment, and 
currently marketed CAL/BDP products are restricted to non-aqueous oil-based formulations that 
are sticky and inconvenient to many patients21. 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 this cream to the Taclonex® Topical Suspension/Daivobet ® 
Gel/Dovobet® Gel. 
The cosmetic qualities of a topical product are of importance for patient adherence to treatment, 
and the purpose of the trial is to compare this topical with the marketed CAL/BDP combination 
gel/topical suspension. The results of the Psoriasis Treatment Convenience Scale will be used as 
secondary endpoint. The scale has been tested for content validity and the trial will be used to 
finalise the psychometric validation.   
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.  
MC2-01 cream contains the same active ingredients at identical concentrations of CAL and BDP 
as the marketed products (w/w 0.005%/0.064%) but in a novel cream formulation that is expected 
to provide better cosmetic convenience to patients than the currently available formulations.  
The side effects reported with CAL/BDP topical formulations been mild and reversible upon 
stopping therapy. Systemic exposure of the MC2-01 cream will be tested under maximum use 
conditions in parallel with this phase 3. For this reason, all patients in the current trial will be 
monitored closely for both for both systemic and local safety with special focus on signs/symptoms 
of hypercalcemia or suppression of HPA axis as well as cardiac safety including periodic 
electrocardiograms (ECGs). 

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In case of inadequate efficacy, the subject can decide to withdraw and then receive alternative 
therapy according to her/his choice. A small 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, and the 
subjects are free to withdraw at any time if they choose.  
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 outcome22.  
3.0 
TRIAL OBJECTIVES AND PURPOSE 
The primary objective is to show therapeutic non-inferiority of MC2-01 cream to active 
comparator, as well as 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 Phase 3, international, randomised, investigator-blind, multicentre, vehicle and 
comparator controlled, parallel-group, 3-arm trial designed to show therapeutic non-inferiority of 
MC2-01 (CAL and BDP) cream to active comparator in subjects with mild-to-moderate psoriasis 
vulgaris.  
Trial subjects will be enrolled at approximately 57 investigative sites in the US. Approximately 
791 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 non-scalp areas of the body (trunk and/or limbs) topically 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 4 weeks (if washout of prohibited medications is required), an 8-week 
treatment period, and a follow-up period of 2 weeks. 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).  
During the treatment period, the investigator will score the disease severity of the subject using 
the physician’s global assessment (PGA), modified Psoriasis Area and Severity Index (mPASI) 

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and body surface area (BSA) involvement; and the subject will perform a disease assessment 
using subject’s global assessment (SGA). The subjects will be asked to complete the 
Dermatology Life Quality Index (DLQI), EuroQOL five dimensions (EQ-5D), Icth by NRS and 
the Psoriasis Treatment Convenience Scale questionnaires. Safety assessments (local skin 
reaction, AEs, laboratory tests, electrocardiogram (ECG), 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 
 
 
4.2 
Trial Endpoints 
4.2.1 
Primary Endpoint  
The primary efficacy endpoint is the proportion of subjects in each treatment group with 
‘treatment success’ at Week 8, defined as a minimum 2-point decrease from Baseline to Week 8 
on the PGA of disease severity on the trunk and 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.     
MC2-01 cream (n= 339) 
Active comparator (n= 339) 
MC2-01 Vehicle cream (n= 113) 

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4.2.2 
Secondary Endpoints 
Secondary endpoints are the following: 
• Percentage change from Baseline in the mPASI score at Week 8; 
• Subject assessment of treatment convenience at Week 8 using a Psoriasis Treatment 
Convenience Scale 
• Change in itch intensity assessed on a numerical rating scale (Itch by NRS) from baseline 
to Week 4 (MC2-01 cream vs MC2-01 cream vehicle) 
• Proportion of subjects with four-point improvement on the numerical rating scale (Itch by 
NRS) from baseline to Week 4 (MC2-01 cream vs MC2-01 cream vehicle) 
4.2.3 
Safety Endpoints 
Safety endpoints include the following: 
• Local skin reaction; 
• AEs and serious adverse events (SAEs); 
• Changes in safety laboratory test results and ECGs; 
• Changes in vital signs and physical examinations. 
4.2.4 
Other Endpoints  
Efficacy 
• PGA success rate at Week 4; 
• Percentage change from Baseline in the mPASI score at Week 4;  
• Number of subjects with PASI 50 (at least 50% reduction in mPASI from Baseline) at 
Week 4 and Week 8; 
• Number of subjects with PASI 75 (at least 75% reduction in mPASI from Baseline) at 
Week 4 and Week 8; 
• Change from Baseline in SGA at Week 4 and Week 8. 
Patient reported outcome 
• 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. 
• Change in itch intensity assessed on a numerical rating scale (Itch by NRS) from baseline 
to Week 1 as well as Week 8 (MC2-01 cream vs MC2-01 cream vehicle) 
 

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5.0 
SELECTION OF TRIAL POPULATION 
5.1 
Subject Population 
Approximately 791 subjects will be enrolled to provide approximately 712 completed subjects 
evaluable for the primary analysis. 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. 
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 trunk and/or limbs that is amenable to topical treatment with a 
maximum of 100 g of trial medication per week. 
4. 
Have a PGA of disease severity of mild or moderate on the body (trunk and/or limbs);  
5. 
An mPASI score of at least 2; 
6. 
Have a treatment area involving 2- 30% of the body surface area (BSA); 
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 be willing to use effective contraception at 
trial entry and until completion. Effective contraception is defined as follows:  
• oral/implant/injectable/transdermal/ 
estrogenic 
vaginal 
ring 
contraceptives, 
intrauterine device, condom with spermicide, diaphragm with spermicide;  
• abstinence or partner’s vasectomy are acceptable if the female agrees to implement 
one of the other acceptable methods of birth control if these conditions do not any 
longer apply. 
5.3 
Exclusion Criteria 
Subjects who fulfill any of the following criteria will be ineligible to participate in the trial: 

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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 trail: 
• Etanercept – within 4 weeks prior to randomisation, 
•  Adalimumab, Alefacept, Infliximab – within 8 weeks prior to randomisation, 
• Ustekinumab – within 16 weeks prior to randomisation, 
• Other products – within 4 weeks/5 half-lives prior to randomisation (whichever 
was longer). 
9. 
Use of systemic treatments that suppress the immune system (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 the baseline visit 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, 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; 
12. Have clinical signs of skin infection with bacteria, viruses, or fungi; 
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; 

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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 
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. 
If, at the time of refusal, a trial product has already been administered, the investigator should 
advise the subject on follow-up safety evaluations. 
In the case of an SAE or development of a condition that would have met the trial safety-related 
exclusion criteria, the subject should be evaluated by the investigator. The investigator should use 
his/her discretion to determine whether the subject should continue treatment with the IP.  
A subject may be withdrawn from the trial at any time at the discretion of the investigator. The 
reasons for early termination are to be fully documented on the eCRF. 
In addition, MC2 reserves the right to end or suspend the trial at any time (see Section 9.2). 
If a subject withdraws from the trial, all efforts will be made to complete a final evaluation if 
possible. The withdrawal procedures for subjects who withdraw during the treatment period are 
the same as those for the End of Treatment visit (Visit 6/Week 8). Subjects who withdraw after 
Visit 6 (Week 8) are to undergo the Visit 7 (Week 10) procedures.  
Subjects discontinued for an AE will be monitored until the AE is resolved, a reasonable 
explanation is provided for the event, or the subject is referred to his/her own primary medical 
doctor. The specific AE in question will be recorded on the appropriate eCRF. 
5.5 
Replacement Policy 
After trial enrolment has been completed, subjects who prematurely discontinue the trial after 
randomisation will not be replaced. 

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6.0 
TRIAL TREATMENTS 
6.1 
Investigational Product 
MC2-01 cream is a combination product, calcipotriene and betamethasone dipropionate, 
administered as a cream formulation for topical administration. One concentration of the trial 
product will be studied: calcipotriene (w/w 0.005%) and betamethasone (w/w 0.064%, as 
dipropionate). The list of inactive ingredients present in MC2-01 cream is presented in the 
Investigator Brochure. 
The MC2-01 vehicle cream will contain the same ingredients as the active formulation without the 
active ingredients. 23 
6.2 
Active Comparator Product 
The active comparator is a marketed CAL/BDP gel/topical suspension, w/w 0.005%/0.064%, 
approved in the US as Taclonex®Topical Suspension and in the rest of the world as Dovobet® Gel 
/Daivobet® Gel. For this phase 3 trial, the reference product will be sourced in the US.  
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. 
6.3 
Dosing Regimen 
Subjects must apply the trial product topically once daily preferable in the evening to affected 
areas on the trunk (including the neck) and/or limbs, i.e., arms (including the back of the hands) 
and legs (including the buttocks and the top of the feet) for 8 weeks. The face, scalp, genitals and 
intertriginous areas should not be treated with the IP.  
Subjects are to record the date and time of application in the subject diary. The weekly dose is not 
to exceed 100 g, and the treated area should not exceed 30% of the BSA. It is preferable that no 
trial product will be applied within 4 hours of on-treatment trial visits. 
Detailed application instructions will be provided in the subject instructions.  
6.4 
Dose Modification 
Subjects classified as clear at any of the on-treatment visits may stop the 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 treatment may be 
restarted at the subject’s discretion. The subject should not discontinue treatment themselves 
between visits, but is only allowed to stop using the treatment on the advice of the investigator at 
a scheduled visit. 

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6.5 
Packaging, Labeling, and Storage 
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 clinical site(s) as tubes 
containing 60 g of product. The MC2-01 cream and MC2-01 cream vehicle are to be protected 
from light and stored at a temperature of 2°- 8°C (35°- 46°F) at the site, and below 25°C (below 
77°F) after dispensing to the subject. 
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 (below 77°F), however 
the product must not be refrigerated.   
6.6 
Assignment to Treatment 
6.6.1 
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 (IWR) system in accordance with a pre-planned computer-generated 
randomisation schedule in a 3:1:3 ratio (MC2-01 cream: MC2-01 cream vehicle: active 
comparator).  
Randomisation will be performed stratified by baseline severity and study site. The central 
randomisation procedure will limit the number of subjects with mild disease (based on the PGA) 
to 30% of the total population. 
Randomisation data will be kept strictly confidential, accessible only to authorised persons, until 
the time of un-blinding.  
A subject who fulfils the trial eligibility requirements will be randomly assigned to treatment.  
6.6.2 
Blinding 
Due to difference in formulation and packaging, it is not possible to double blind the IPs. To keep 
the trial investigator blinded, packing and labeling 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 be therefore handled by a 
designated third person. Individual bottles/tubes of IPs will be inaccessible to the investigator(s) 

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and other trial staff involved in the evaluation of subjects and conduct of the trial. 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.  
6.7 
Prior, Concomitant, and Prohibited Therapy 
All medications, including over-the-counter (OTC) drugs, 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. 
6.7.1 
Washout of Prohibited Medications Prior to Enrollment 
A washout period of up to 4 weeks must be completed if the subject has been treated with any 
medication as specified in the exclusion criteria (Section 5.3). 
6.7.2 
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 psoriasis therapies;  
• 
Use of oral systemic treatments with a possible effect on psoriasis (e.g., methotrexate, 
apremilast, retinoids, PDE4 inhibitors, corticosteroids, and other immunosuppressants). 
• 
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. 
 
6.7.3 
Allowed Treatment on the Face, Scalp, Skin Folds and Genital Skin Only 
Subjects may receive laser treatment and use shampoos containing the active ingredients zinc 
pyrithione, salicylic acid, selenium sulfide, ketoconazole, or tar. Subjects may use an emollient on 
the face, scalp, skin folds, and genital skin. 

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6.8 
Treatment Compliance 
Records of trial product used and dosages administered will be kept during the trial. The trial 
monitor will note product accountability during site visits and at the completion of 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 specified. In addition, 
subjects will be asked to complete a dosing diary during the treatment period as a measure of 
treatment compliance.  
Subjects who are consistently 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 will be weighed to determine the amount 
of the IP used per treatment phase. 
7.0 
VISIT SCHEDULE AND ASSESSMENTS 
7.1 
Trial Procedures 
The visit schedule and assessments are summarised in Table 1-1.  
7.2 
Trial Visits and Assessments 
7.2.1 
Visit 0/Screening (Day –30 to Day 0) 
Screening procedures should be completed no more than 30 days prior to Visit 1/Baseline (Day 0). 
Visit 0/Screening and Visit 1/Baseline can occur on the same day if no washout of prohibited 
medications is required. The following screening procedures will be performed at the screening 
visit: 
• 
Review trial information with subject and obtain written informed consent.  
• 
Review inclusion and exclusion criteria with the subject to determine the subject’s eligibility. 
• 
Collect medical history;  
o complete skin disease history including the year the subject was diagnosed with 
psoriasis 
o other medical/surgical history if the subject received concomitant medication for the 
condition 
o all other medical/surgical conditions within the last 12 months if the subject did not 
receive concomitant medication 
o demographic information, including skin phenotype, using the Fitzpatrick 
classification scale. 

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• 
Review and record prior medication (used within the previous 30 days) and concomitant 
medication (medications currently used). 
• 
Review and record any current medical diagnoses. 
• 
Perform the following investigator assessments:  
o PGA of disease severity,  
o mPASI scoring,  
o Determination of involved BSA. 
• 
Perform a urine pregnancy test (UPT) in female subjects of childbearing potential and instruct 
these female subjects to use approved form(s) of contraception.  
• 
If a washout period is required, initiate the washout period and schedule the Visit 1/Baseline 
(Day 0) visit.  
• 
If the Visit 0/Screening and Visit 1/Baseline (Day 0) procedures are being performed on the 
same day, perform the procedures specified in Section 7.2.2. 
7.2.2 
Visit 1/Baseline (Day 0) 
If a prior Screening visit did not occur, perform the procedures listed in Section 7.2.1. 
The following procedures are to be performed at Visit 1/Baseline: 
• 
Review inclusion and exclusion criteria to ensure that the subject is qualified for trial 
participation.  
• 
Have the subject perform the following patient-reported outcomes (PROs): 
o SGA of disease severity 
o DLQI questionnaire  
o EQ-5D questionnaire. 
o Itch by NRS  
• 
Perform a physical examination: including height and weight (without shoes) and vital signs 
(systolic and diastolic blood pressure and heart rate).  
• 
Review and record any medication(s) used in the period since Visit 0/Screening. 
• 
Perform a UPT for females of childbearing potential. Ensure that female subjects of 
childbearing potential are using approved method(s) of contraception. 
• 
Perform a 12-lead ECG. 
• 
Record any AEs that occurred after the informed consent form was signed.  
• 
Assess treatment area for local skin reactions. 
• 
Collect blood and urine samples for laboratory analyses. 

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• 
Perform the following investigator assessments:  
o PGA of disease severity,  
o mPASI scoring,  
o Determination of involved BSA. 
• 
Perform randomisation. 
• 
Dispense the IP and diary. Provide instructions to the subject on IP application.  
• 
Schedule the next visit, at approximately the same time of day as the current visit. 
7.2.3 
Visit 2/ Week 1 (Day 7 ±2)  
• 
Have the subject perform the following PROs: 
o SGA of disease severity, 
o Psoriasis Treatment Convenience Scale, 
o DLQI questionnaire, 
o Itch by NRS 
• 
Collect the IP from the subject.  
• 
Assess compliance as specified in Section 6.8. 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Perform the following investigator assessments of efficacy:  
o PGA of disease severity,  
o mPASI scoring.  
• 
Assess treatment area for local skin reactions. 
• 
Record any AEs. 
• 
Dispense the IP. 
• 
Schedule the next visit at approximately the same time of day as the current visit. 
7.2.4 
Telephone Call (TC)/Visit 3/Week 2 (Day 14 ±2) 
The subject is contacted by phone for evaluation of safety and adherence to the treatment schedule.  
Can be an on-site visit if judged necessary by the Investigator.  
7.2.5 
Visit 4/Week 4 (/Day 28 ±2) 
• 
Have the subject perform the following PROs: 
o SGA of disease severity, 
o DLQI questionnaire, 

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o EQ-5D questionnaire, 
o Psoriasis Treatment Convenience Scale. 
o Itch by NRS  
• 
Collect the IP from the subject.  
• 
Assess compliance as specified in Section 6.8. 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Collect blood and urine samples for laboratory analyses. 
• 
Perform a physical examination; including weight without shoes, and measurement of vital 
signs (systolic and diastolic blood pressure and heart rate).  
• 
Perform a UPT for females of childbearing potential. Ensure that female subjects of 
childbearing potential are using approved method(s) of contraception. 
• 
Perform a 12-lead ECG. 
• 
Perform the following investigator assessments of efficacy:  
o PGA of the disease severity,  
o mPASI scoring,  
o Determination of involved BSA. 
• 
Assess treatment area for local skin reactions. 
• 
Record any AEs. 
• 
Dispense the IP. 
• 
Schedule the next visit. 
7.2.6 
Visit 5/Week 6 (Day 42 ±2) 
• 
Have the subject perform the PRO: SGA. 
• 
Collect the IP from the subject.  
• 
Assess compliance as specified in Section 6.8. 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Perform the following investigator assessments of efficacy:  
o PGA of the disease severity,  
o mPASI scoring.  
• 
Assess treatment area for local skin reactions. 
• 
Record any AEs. 
• 
Dispense the IP. 

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• 
Schedule the next visit. 
7.2.7 
Visit 6/Week 8 (End of Treatment) (Day 56 ±2) 
• 
Have the subject perform the following PROs: 
o SGA of disease severity, 
o DLQI questionnaire, 
o EQ-5D questionnaire, 
o Psoriasis Treatment Convenience questionnaire. 
o Itch by NRS 
• 
Collect any unused trial medication, the subject diary, and any other trial materials from the 
subject. 
• 
Assess compliance as specified in Section 6.8. 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Collect blood and urine samples for laboratory analyses.  
• 
Perform a physical examination; including weight without shoes, and measurement of vital 
signs (systolic and diastolic blood pressure and heart rate).  
• 
Perform a UPT for females of childbearing potential. Ensure that female subjects of 
childbearing potential are using approved method(s) of contraception. 
• 
Perform a 12-lead ECG. 
• 
Perform the following investigator assessments of efficacy:  
o PGA of the disease severity,  
o mPASI scoring,  
o Assess involved BSA. 
• 
Assess treatment area for local skin reactions. 
• 
Record any AEs. 
• 
Schedule the next visit. 
7.2.8 
Visit 7/Week 10 (Follow Up /End of Trial) (Day 70 ±2 days) 
• 
Collect any remaining trial materials from the subject. 
• 
Review any concomitant medication used since the previous trial visit. 
• 
If required (i.e., if albumin-corrected serum calcium is above the reference range at the last 
on-treatment visit; or if follow-up is required of a previous abnormal and significant 
laboratory result), collect samples for follow-up laboratory analysis. 
• 
Assess treatment area for local skin reactions. 

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• 
Record any AEs. 
• 
Release subject from the trial. 
7.2.9 
Early Termination 
If a subject withdraws from the trial prior to the Visit 6/Week 8 (End of Treatment) visit, the 
subject is to return to the site to return the trial medication. All End of Treatment procedures should 
be performed. 
• 
Have the subject perform the following PROs: 
o SGA of disease severity, 
o DLQI questionnaire, 
o EQ-5D questionnaire, 
o Psoriasis Treatment Convenience questionnaire. 
o Itch by NRS 
• 
Collect all trial materials from the subject, including unused trial medication and the subject 
diary. 
• 
Assess compliance as specified in Section 6.8. 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Perform a physical examination; including weight without shoes, and measurement of vital 
signs (systolic and diastolic blood pressure and heart rate).  
• 
Perform a UPT for females of childbearing potential.  
• 
Perform a 12-lead ECG. 
• 
Collect blood and urine samples for laboratory analyses.  
• 
Perform the following investigator assessments of efficacy:  
o PGA of the disease severity,  
o mPASI scoring,  
o Assess involved BSA. 
• 
Assess treatment area for local skin reactions. 
• 
Record any AEs. 
If a subject withdraws from the trial after the Visit 6/Week 8 (End of Treatment) visit but before 
the Visit 7/Week 10 (End of Trial) visit, the subject is to return to the site. The following 
procedures should be performed:  
• 
Collect all trial materials from the subject, including unused trial medication. 

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• 
Review any concomitant medication used since the previous trial visit. 
• 
If required (i.e., if albumin-corrected serum calcium is above the reference range at the last 
on-treatment visit; or if follow-up is required of a previous abnormal and significant 
laboratory result), collect samples for follow-up laboratory analysis. 
• 
Record any AEs. 
• 
Assess treatment area for local skin reactions. 
7.2.10 
Unscheduled Visit and Telephone Calls 
An unscheduled visit may be performed at any time during the trial if judged necessary by the 
Investigator, such as for a severe reaction and clinically significant AE. Details of the event must 
be recorded in the subject’s records. 
7.3 
Investigator Assessments 
The investigator assessments are to be performed by a dermatologist, a physician with at least 
1 year of experience in dermatology, or a Physician Assistant with at least 2 year of experience in 
dermatology. For physicians and Physician Assistants who do not fulfill the requirement regarding 
dermatological experience and other state licensed professionals who have the ability to diagnose, 
treat and prescribe medications, the person must be preapproved by the sponsor. The assessments 
are to be performed as specified in the visit schedule (Table 1-1). 
7.3.1 
Physician’s Global Assessment 
The Physician’s Global Assessment (PGA) measures the investigator’s or designee’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 7-1. The PGA assessment will represent the average lesion severity 
on the trunk and limbs. 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. 

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Table 7-1 
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 coverering 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 
 
7.3.2 
Extent and Severity of Redness, Thickness, and Scaliness 
At all visits, the investigator or designee will assess the extent and severity of the subjects’ 
psoriasis using an mPASI scoring system (excluding scalp, face, and flexures). 
The extent of psoriatic involvement will be recorded for each of the 3 areas (arms, trunk, and legs) 
using the following scale: 
0  =  no involvement 
1  =   < 10% 
4  =  50% - 69% 
2  =  10% - 29% 
5  =  70% - 89% 
3  =  30% - 49% 
6  =  90% - 100% 
 

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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) 
 
7.3.3 
Body Surface Area Involvement of Psoriasis Vulgaris 
The investigator or designee will assess the extent of the subject’s psoriatic involvement on the 
trunk and limbs (excluding scalp, face, and flexures) at the visits specified in Table 1-1.  
The total psoriatic involvement on the trunk and limbs (excluding genital and intertriginous areas) 
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 purpose 
of this is to obtain an estimate of the area on the trunk and limbs to be treated with trial medication. 
7.3.4 
Local Skin Reactions 
The local skin reaction involves signs assessed by the investigator or designee and symptom 
reported by the subject. 
The investigator will assess the treatment area and/or immediate surrounding for the following 
identified signs:  

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• 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 7-2. The most severe intensity observed for each category of the local skin reaction 
assessment is to be recorded. 
 
The subject will assess burning and pain after application. The investigator or designee  
will explain the scores in Table 7-2 and the subject will tell which one to mark.  
Signs and symptoms fulfilling the AE definition should be reported as AEs. 
 
 
 
 
 

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Table 7-2 
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 
Coarse 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 
Subject Assessment 
 
0 (Absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Burning 
or 
pain  
after application 
None 
Barely present and 
disappears within 
few minutes 
Distinct and last for 
up to an hour 
Pronounced and 
last for several 
hours  
 
7.4 
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 1-1).   

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7.4.1 
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. 
7.4.2 
Dermatology Life Quality Index (DLQI) 
The DLQI24 is a validated questionnaire consisting of 10 questions relating to the degree to which 
the subject’s skin condition affected their daily activities.  
7.4.3 
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)25. 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 self-reported description of the 
subject’s current health in 5 dimensions i.e., mobility, self-care, usual activities, pain/discomfort, 
and anxiety/depression. 
7.4.4 
The Psoriasis Treatment Convenience Scale 
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 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? 
5. How much did treating your skin disrupt your daily routine? 
6. Overall, how satisfied were you with the medical treatment? 
7.4.5 
Itch by Numerical Rating Scale (Itch by NRS) 
To assess the intensity of psoriasis itch, a numerical rating scale is used. The Itch by NRS is a  
10-point scale with the ends representing the two extremes of itch intensity, i.e., from 0 (no itch 
at all) to 10 (worst itch one can imagine). The subject should rate the worst intensity of itch 
within the previous 24 hours. 

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7.5 
Assessment of Pharmacokinetics (not applicable)  
Pharmacokinetics will not be assessed in this trial. 
 
7.6 
Assessment of Safety 
7.6.1 
Adverse Events 
7.6.1.1 
Adverse Events Assessments 
The investigator or designee is responsible for obtaining, assessing, and documenting all AEs 
during the study. Adverse Events information will be collected from the time of the signature of 
the informed consent form until the end of the study. An AE is an untoward medical occurrence 
in any subject during the trial which does not necessarily have a causal relationship with the trial 
drug treatment.  
All AEs will be documented in the eCRF, including a description of each AE, AE relationship to 
trial product 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 to the United BioSource Corporation (UBC) within 24 hours of 
awareness.  
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. 
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. 
Any AE that is considered related to the trial product 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 the MC2 or designee. 
The outcome of an AE will be classified as recovered, recovered with sequelae, 
recovering/resolving, ongoing, or death. 
7.6.1.2 
Timing 
AEs will be collected/assessed from the time of the signature of the informed consent form by the 
subject and first trial-related activity performed.  

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7.6.1.3 
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 does 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). 
7.6.1.4 
Relationship of an Adverse Event to Trial Treatment 
The investigator is responsible to assess the relationship of an AE to the IP using good clinical 
judgment and the following definitions: 
Not Related 
The AE is clearly explained by another cause not related to the trial 
product 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 trial product are temporally related, but 
the AE can be explained equally well by causes other than the trial 
product administration 
Probably Related 
The AE and use of trial product are temporally related, and the AE is 
more likely explained by trial product administration than by other 
causes 
Definitely Related 
The AE and trial product 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 
7.6.1.5 
Unexpected Adverse Events 
Any AE assessed as 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 

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MC2-01 Investigator’s Brochure26 (for MC2-01 cream) or Taclonex®Topical Suspension 
prescribing information23 (for active comparator). 
 “Unexpected” as used in this definition, also refers to AEs that are mentioned in the Investigator’s 
Brochure or product prescribing information 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. 
7.6.1.6 
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 as an AE. 
The maximum weekly dose should not exceed 100 g, and the treated area should not be >30% of 
the body surface area. 
Use above the recommended dose 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 
7.6.1.7 
Pregnancy 
Any pregnancy occurring from date of the Informed Consent signature until study completion 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 the pregnancy (see 
Section 13.2).  
Investigator must actively follow-up, document and report to MC2 or designee the progress of the 
pregnancy until outcome is reached.  
7.6.2 
Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose: 
• 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  

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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 
hospitalization may be considered an SAE when, based on appropriate medical judgment, they 
may jeopardize 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 hospitalizations that are known at the time of signing the 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 13.2). The investigator will 
document such events in the best possible detail on the SAE Report Form.  
A suspected unexpected serious adverse reaction (SUSAR) is an SAE that is both unexpected 
(not consistent with the current Investigator’s Brochure for MC2-0126 gel or Taclonex® Topical 
Suspension prescribing information23) 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 or 
designee will report SAEs and other events requiring expedited reporting to regulatory 
authorities as required.  
Investigator instructions for reporting SAEs are provided in Section 13.2. 
7.6.3 
Safety Laboratory Assessments 
Blood and urine samples will be collected for routine safety laboratory tests and urinalysis as 
specified in the visit schedule (Table 1-1). Clinical laboratory specimens will be analysed by a 
central licensed and accredited laboratory facility according to the laboratory’s standard operating 
procedures. The following tests will be performed:   
• 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 serum/urine 
pregnancy testing at Screening/Baseline visit(s) as specified in Section 7.6.4. 

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The investigator may collect additional blood or urine samples to repeat any laboratory test that is 
abnormal post-dosing and is considered clinically significant. Abnormal laboratory results at the 
last 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. 
If serum calcium is above the reference range at Visit 6/Week 8 visit, a follow-up test must be 
performed at the next visit (Visit 7/Week 10). 
7.6.4 
Pregnancy Testing 
Female subjects of child-bearing potential will undergo a routine urine pregnancy test (UPT) at 
the Visit 0/Screening and/or Visit 1/Baseline before any trial-specific procedures are performed. 
If the UPT is positive, the subject will not be permitted to enroll in the trial.  
Routine UPTs will be repeated at Visit 4/Week 4 and Visit 6/Week 8/End of Treatment (or Early 
Termination). 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.  
All pregnancies should be immediately reported to the sponsor or designee and followed through 
to resolution (i.e., delivery, miscarriage, or abortion). The report should be submitted within the 
same timelines as an SAE (within 24 hours of knowledge), although a pregnancy per se is not 
considered an SAE. 
7.6.5 
Vital Signs 
At Visit 1/Baseline, Visit 4/Week 4 and Visit 6/Week 8, the investigator or designee will take 
measurements of vital signs, including blood pressure and heart rate (pulse) with the subject in the 
sitting position with approximately 5 minutes rest prior to measurement. The same arm is to be 
used for all measurements. 
7.6.6 
Physical Examination 
At Visit 1/Baseline, Visit 4/Week 4, and Visit 6/Week 8, the investigator or designee will complete 
a general physical examination including measurements of height (at Screening only) and weight 
(with indoor clothing and without shoes).  

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During the trial, any new clinically significant findings of signs/symptoms that could indicate 
systemic safety will be reported as AEs.  Any signs/symptoms of hypercalcemia or suppression of 
HPA axis will be carefully monitored and if necessary the subject will be withdrawn from the trial. 
The Fitzpatrick skin type will be assessed according to the classification scheme in Table 7-3. 
Table 7-3 
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 
 
7.6.7 
Electrocardiogram 
A 12-lead ECG will be recorded at Visit 1 (Day 0/Baseline), Visit 4 (Week 4), and Visit 6 (Week 
8) or the Early Termination visit if the subject withdraws prior to Week 8. Recording will take 
place after 5 min rest in supine position.  
All printed ECGs will be evaluated by the investigator or a designee, and will also be sent to a 
central laboratory for interpretation. Additional (unscheduled) ECGs can be recorded for safety 
reasons at any time based on the judgment of the investigator.  
ECG s with clinically significant findings as determined by the Investigator will be reported as 
medical history if detected at Visit 1. At subsequent visits, any new clinically significant finding 
as determined by the Investigator will be reported as an AE. Any ECG abnormalities will be 
carefully monitored and if necessary the subject will be withdrawn from the trial. 
7.7 
Appropriateness of Measurements 
The assessments to be used in this trial are the standardised and most widely accepted methods for 
evaluating safety and efficacy in studies of psoriasis. 

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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 and un-blinded. 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 centre and baseline severity. The aim is to randomise 14 subjects or 
more at each site. It is planned that the data from all centres that participate in this protocol 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. To investigate the homogeneity of the primary efficacy outcome across analysis sites, a 
Forest plot will be prepared showing the PGA treatment success rate difference of each analysis 
site. Outliers will be investigated and sensitivity analysis excluding outliers may be performed if 
deemed necessary. 
8.2 
Sample Size and Power Considerations 
The primary endpoint is the proportion of subjects who achieve a minimum 2-point decrease from 
Baseline in PGA at Week 8. The primary endpoint will be used for the non-inferiority evaluation.  
The sample size calculation is based on the non-inferiority margin for the difference in PGA 
response.  
Non-inferiority margin: 
The non-inferiority margin was determined according to the draft Food and Drug Administration 
(FDA)-Guidance for Industry: Non-inferiority Clinical Trials27 as a fixed margin.  
A summary of responders, based on the PGA, at Week 8 from 3 randomised trials of calcipotriene 
and betamethasone dipropionate gel11;28;29 is shown below in order to determine the statistical 
margin M1 and the clinical margin M2. The clinical margin M2 is used in the determination of 
sample size. 

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Daivobet 
Vehicle 
Daivobet - Vehicle 
Trial 
N 
PGA 
success % 
N 
PGA 
success % 
% 
99% CI 
Menter et al, 2013  28 
482 
29.0 
95 
6.3 
22.7 
(14.4, 31.1) 
Langley et al, 201129 
183 
39.9 
91 
5.5 
34.4 
(23.2, 45.6) 
Fleming et al, 201011 
162 
27.2 
40 
0 
27.2 
(18.2, 36.2) 
 
Total  
 
 
 
 
26.2 
(19.9, 32.6) 
CI = confidence interval 
 
The lower 99%-confidence limit of the response difference between calcipotriene/betamethasone 
dipropionate gel and vehicle was calculated to be 19.9%. Therefore, the prespecified M1 margin 
was determined to be 19.9%, a conservative choice for the active control effect size. The largest 
loss of effect that would be clinically acceptable (M2) is set to 10% points. 
Assumptions for the non-inferiority comparison: 
• The lower non-inferiority boundary for M1 is set to 19.9% for the difference between 
vehicle and active comparator in response rates according to PGA. 
• The lower non-inferiority boundary for M2 is set to 10% points for the difference between 
MC2-01 cream and active comparator in response rates according to PGA. 
Assumptions for sample size calculation: 
• The response of active comparator is assumed to be 30%. 
• The absolute difference of MC2-01 cream and active comparator is assumed to favor MC2-
01 cream by at least 2.5 percentage points. The treatment difference between MC2-01 
cream and active comparator was estimated based on preliminary results from a plaque 
psoriasis trial that showed slightly better efficacy for MC2-01 cream compared with active 
comparator.  
• The power should be at least 90%. 
• The error probability is set to 0.05 for a 2-sided test. 
Under these assumptions, a sample size of N=305 per active treatment group is calculated. 
Assuming 90% completion rate of the randomised subjects, a total sample size of N=339 per active 
treatment group is required to be randomised.  

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The comparison to vehicle to show superiority of MC2-01 cream and active comparator will need 
N=103 per treatment group under the assumption of a vehicle responder-rate of 11%, a response 
rate of at least 30% for the MC2-01 cream and active comparator, and 90% power. Following a 
3:1:3 randomisation ratio, 113 subjects will be randomised to receive the MC2-01 vehicle cream 
(assuming a 90% completion rate).  
A total enrolment of approximately 791 subjects is planned to have approximately 712 completed 
subjects.  
8.3 
Analysis Populations 
The analysis populations are defined as follows:  
• Intent to Treat (ITT) population will include all randomised subjects.  
• Per Protocol (PP) population will include subjects in the ITT population who complete the 
trial without any major protocol violations.The composition of the PP population will be 
determined and documented in blind reviews of the database conducted prior to un-
blinding the trial database. Subjects may be excluded from 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 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 Week 4 to Week 8  
o Noncompliance with the trial treatment regimen; adherence to the treatment 
schedule is defined as application of IP as per subject diary for at least 80% of the 
days from Day 1 to Week 8; 
 
• Safety population will include all subjects who were randomised and dispensed the trial 
medication at Randomisation/Day 0, excluding subjects who return all the trial medication 
unused.  
The ITT and PP Population will be used for the analyses of the primary efficacy endpoint. The PP 
population will be considered as the primary population for analyses of therapeutic non-inferiority 

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of MC2-01vs active comparator. The ITT analysis will be considered as the primary population 
for the analysis of superiority of MC2-01 and active comparator vs. vehicle. A similar approach 
will be used for the secondary efficacy endpoints. The Safety Population will be used for the 
analyses of safety endpoints. 
8.4 
Handling of Missing Data 
For analyses using the PP population, no imputations will be made for missing data. 
For analyses using the ITT population, a variety of methods will be used to impute missing primary 
efficacy endpoints, including multiple imputation (MI), last-observation-carried forward (LOCF), 
baseline-observation-carried-forward (BOCF), and non-responder imputation (NRI). MI will be 
the primary imputation method. Sensitivity analyses utilising LOCF, BOCF, and NRI will also be 
performed to assess the robustness of imputation assumptions.  
Multiple imputation: Post-baseline missing PGA data will be multiply 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. The 
imputation model will include: duration (days) of psoriasis, prior systemic biologic use for 
psoriasis (yes/no), baseline PGA score, and PGA scores at weeks 1, 4, 6, and 8. The number of 
imputations will be set to 100. Similar multiple imputation methods will be used for other efficacy 
endpoints.  
8.5 
Analysis of Efficacy 
8.5.1 
Primary Efficacy Endpoint(s) 
The primary efficacy endpoint is the proportion of subjects in each treatment group with ‘treatment 
success’ at Week 8, defined as a minimum 2-point decrease from Baseline to Week 8 on the 
Physician’s Global Assessment (PGA) of disease severity on the trunk and limbs; i.e. 0 (clear) or 
1 (almost clear) disease for subjects with moderate disease at Baseline; or a score of 0 (clear) for 
subjects with, a score of mild disease at Baseline.  
8.5.1.1 
Analysis of the primary endpoint  
Superiority Analysis 
The primary analysis of superiority will be based on the ITT population using multiple imputation 
The PGA response rate for MC2-01 cream and for active comparator at Week 8 will first be 
compared with that for MC2-01 cream vehicle at Week 8 for a superiority evaluation. The 
superiority will be tested using a logistic model with treatment, baseline value of PGA and analysis 
site as independent variables. Superiority will be achieved at the 5% significance level (p<0.05; 
two-sided). For the superiority analysis using MI, the estimate and standard error of the log odds 

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ratio will be evaluated for each of the multiple imputed datasets and combined in PROC 
MIANALYZE.  
Non-inferiority (NI) analysis 
If and only if superiority to MC2 cream vehicle for both MC2-01 cream and for active comparator 
can be claimed at the 5% significance level, the non-inferiority (NI) analysis of the primary 
endpoint will be conducted based on the PP Population. The PGA success rate of MC2-01 cream 
at Week 8 will be compared with that of active comparator at Week 8, using a therapeutic non-
inferiority margin of 10% points.  
The percentage of subjects in each group with treatment response will be calculated along with its 
95% confidence interval (CI) using normal approximation. A 95%, 2-sided CI on the difference 
between MC2-01 cream and active comparator will be computed using normal approximation. 
MC2-01 will be considered non-inferior to Active Comparator if the lower bound of the 2-sided 
95% CI is ≥ -10% points. 
8.5.1.2 
Sensitivity Analyses  
As sensitivity analyses, the analyses of superiority will also be made based on the ITT population 
using other imputation methods than MI (LOCF, BOCF, NRI). Further an analysis based on the 
PP population and using complete case analysis with no imputation of missing data will be made. 
The non-inferiority analysis of the primary endpoint will also be performed based on the ITT 
population using a variety of imputation methods as sensitivity analyses (MI, LOCF, BOCF, NRI) 
For the sensitivity non-inferiority analysis using MI, the treatment difference will be evaluated for 
each of the multiple imputed datasets using PROC FREQ with RISKDIFF option. The estimates 
and standard errors of the response rate difference based on the imputed datasets will be combined 
by applying Rubin’s rules in PROC MIANALYZE and the 95% CI of the difference will be 
computed. 
8.5.2 
Secondary Efficacy Endpoints 
Secondary endpoints are the following: 
• Percentage change from Baseline in the mPASI score at Week 8;  
o Superiority evaluation: The percentage change will be compared between MC2-01 
cream vs. vehicle and active comparator vs. vehicle for superiority using an analysis of 
covariance (ANCOVA) model with treatment, baseline PGA severity (mild/moderate), 
baseline mPASI and study site as independent variables. (See derivation of alpha level 
below). The analysis will be based on the ITT population using multiple imputation.  

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o Non-inferiority evaluation: The percentage change will be compared between MC2-01 
cream and active comparator using a similar model as for the evaluation of superiority. 
Non-inferiority will be claimed if the lower limit of the relevant two-sided CI (see 
derivation of alpha level below), derived from the difference in LSMEANS, will be  
≥ -10%. The analysis will be based on the PP population with no imputation of missing 
data. 
• Subject assessment of treatment convenience at Week 8 using a Psoriasis Treatment 
Convenience Scale (PCTS)  
o Superiority evaluation: PCTS will be compared for superiority between MC2-01 
cream and active comparator using an ANOVA model with treatment and trial site as 
independent variables; superiority will be claimed if the lower limit of the relevant 
two-sided CI (see derivation of alpha level below), derived from the difference in 
LSMEANS, will be >0. The analysis will be based on the ITT population. PTCS 
score will be calculated as sum of questions 1 to 5. The score is to be calculated if at 
most two of the questions have missing answers, in which case the missing answers 
will be imputed from the mean of the answered questions. If more than two questions 
have missing answers, the PTCS score will be considered as missing. A PTCS score 
is defined as valid, if subjects have used the study medication at some point within 7 
days prior to the day of the assessment. A PTCS score is considered as invalid if 
subjects have discontinued study medication for more than 7 days prior to the day of 
assessment. Invalid measurements will not be applied in the analysis of that visit. 
Missing and invalid PTCS scores will be imputed using the last valid measure prior to 
the visit.  This approach corresponds to a ‘PTCS while on treatment’ estimand. The 
PTCS will be psychometrically tested in the trial. 
• Change in itch intensity assessed on a numerical rating scale (Itch by NRS) from baseline to 
Week 4: 
o  Superiority evaluation. (MC2-01 cream vs MC2-01 cream vehicle). Superiority 
between MC2-01 cream and vehicle will be assessed by using an ANCOVA model 
with treatment, baseline PGA severity (mild/moderate), baseline Itch by NRS value 
and analysis site as independent variables. The primary analysis will be based on the 
ITT population, using multiple imputation 
• Percentage of subjects with four-point improvement on the numerical rating scale (Itch by 
NRS) from baseline to Week 4 
o Superiority evaluation (MC2-01 cream vs MC2-01 cream vehicle). The analysis is 
made on the subgroup of subjects from the ITT populations with Itch (assessed by 

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NRS) ≥ 4 at baseline. Superiority between MC2-01 cream and vehicle will be 
assessed by using a logistic regression model with treatment, baseline PGA severity 
(mild/moderate), baseline Itch by NRS value and analysis site as independent 
variables. Missing data will be imputed using multiple imputations. 
The global Type-I error will be controlled by the following testing procedure: 
1. 
Secondary endpoints will be tested only if the primary endpoint will reject the Null-
hypothesis; 
2. 
The two secondary endpoints ‘Percentage reduction from Baseline in the mPASI score at 
Week 8, and Subject assessment of treatment convenience at Week 8 using a Psoriasis 
Treatment Convenience Scale will be tested with a loopback procedure30 with initial error 
probability weights 2/3 for H1 (mPASI) and 1/3 for H2 (subject assessment of treatment 
convenience), resulting in α1=0.0333 and α2=0. 0167. If any of the Null-hypotheses can be 
rejected, the respective error probability will be shuffled to the other hypothesis 
3. 
If and only if both non-inferiority of MC2-01 to active comparator with respect to Percentage 
reduction from Baseline in mPASI as well as superiority of MC2-01 vs. active comparator 
with respect to Psoriasis treatment convenience scale has been demonstrated, superiority of 
MC2-01 vs vehicle with respect to the below endpoints will be tested in a hierarchical manner 
based on a significance level of 5%: 
• Change in itch intensity assessed on a numerical rating scale (Itch by NRS) from baseline 
to Week 4 
• Percentage of subjects with four-point improvement on the numerical rating scale (Itch 
by NRS) from baseline to Week 4 (In the subgroup of subjects with an NRS score ≥ 4 at 
baseline) 
All secondary endpoints will be described using summary statistics. For mPASI and NRS, absolute 
values, absolute reduction, and percentage reduction from baseline will be summarised using 
mean, median, SD, quartiles and ranges for each treatment group by visit. Frequency counts and 
percentages of NRS 4-point improvement responders will be provided for each treatment group 
by visit. For PTCS score, absolute values will be summarized using descriptive statistics for each 
treatment group by visit. 
 
 

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8.5.3 
Other Endpoints 
Other endpoints will be the following: 
Efficacy 
• PGA success rate at Week 4; 
• Percentage change from Baseline in the mPASI score at Week 4; 
• Number of subjects with PASI 50 (at least 50% reduction in mPASI from Baseline) at Week 
4 and Week 8; 
• Number of subjects with PASI 75 (at least 75% reduction in mPASI from Baseline) at Week 
4 and Week 8. 
• Change from Baseline in SGA at Week 4 and Week 8; 
Patient reported outcomes 
• Change DLQI score at Week 4 and Week 8; The DLQI will be scored according to the 
developer instructions. Missing values, if any will be incorporated based on the developers 
scoring instructions. The DLQI will also be summarised by the following domains: 
symptoms and feelings, daily activities, leisure, work and school, personal relationships, and 
treatment. 
• Change in EQ-5D score at Week 4 and Week 8. The EQ-5D will be scored according to the 
developer instructions 
• Change in itch intensity assessed on a numerical rating scale (Itch by NRS) from baseline to 
week 1 as well as from baseline to Week 8 (MC2-01 cream vs MC2-01 cream vehicle) 
Other efficacy endpoints (PASI 50 and PASI 75) will be analysed following the same method as 
described for the primary efficacy analysis, except that no formal non-inferiority test will be 
conducted.  
Change from Baseline in SGA at Week 4 and Week 8 will be analysed using an ANCOVA model 
with treatment, baseline PGA severity (mild/moderate) baseline SGA and study site as independent 
variable. The subject convenience data will be summarised using summary statistics for each 
treatment group. 
The Patient reported outcomes DLQI, EQ-5D, and Itch by NRS will be analysed using an 
ANCOVA model with treatment, baseline PGA severity (mild/moderate), analysis site and 
respective baseline patient reported outcome as independent variables. 
Statistical analyses for the other endpoints will be exploratory only and not for statistical inference. 

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8.6 
Analysis of Safety 
The assessment of safety will be based mainly on the frequency of AEs and on the number of 
laboratory values that fall outside of predetermined ranges. AEs will be presented in data listings 
and summarised by frequency and severity for each treatment group. Laboratory and vital sign 
data will be presented in data listings. Abnormal laboratory findings will be presented. The 
analysis of safety will be described in the SAP. 
8.6.1 
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) will be tabulated separately for each treatment group by severity and relationship to 
drug.  
8.6.2 
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 intensities, scored as 0=none, 1=mild, 2=moderate, or 3=severe, will be summarised by 
trial visit for each of the LSR categories. 
For the LSR sum score, the Area Under the Curve (AUC) will be calculated for each subject: 1) 
from Baseline to Week 1; 2) from beginning of Week 1 to end of Week 4; and 3) from beginning 
of Week 5 to End of Trial and 4) from Baseline to End of Trial.  These parameters will be compared  
between treatment groups using  ANOVA. 
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. 
8.6.3 
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. 

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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 
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 reserves the right to terminate or suspend the trial at any time. 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. 
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. The identification of any data to be recorded directly on the eCRFs is 
to be considered source data.  
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 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 or guardian 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 
12.5 
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. 
12.6 
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 Un-blinding 
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 Monitor (or designee) 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 Monitor or 
designee. 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. 

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13.2 
Reporting of Serious Adverse Events and Pregnancies 
13.2.1 
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 UBC using the following 
e-mail or fax-number:  
Email: EUSafety@ubc.com 
Fax number:  +41 225 964 446 
 
 
13.2.2 
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 electronically to 
the UBC using the SAE Reporting fax number within 24 hours of first knowledge of the SAE.  
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.  
14.0 
INSURANCE 
MC2 has taken out appropriate insurance policies covering the subjects in the clinical trial in 
accordance with applicable laws and regulations. 
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 
REFERENCE LIST 
 
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psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol 
2009;60:218-224. 
 
(2)  Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis 
and psoriatic arthritis. J Autoimmun 2010;34:J314-J321. 
 
(3)  Schafer T. Epidemiology of psoriasis. Review and the German perspective. Dermatology 
2006;212:327-337. 
 
(4)  Nestle FO, Kaplan DH, Barker J. Mechanisms of Disease: Psoriasis. N Engl J Med 
2009;361:496-509. 
 
(5)  Griffiths CE, Barker J. Pathogenesis and clinical features of psoriasis. Lancet 
2007;370:263-271. 
 
(6)  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;57:963-971. 
 
(7)  Dubertret L, Mrowietz U, Ranki A et al. European patient perspectives on the impact of 
psoriasis: the EUROPSO patient membership survey. Br J Dermatol 2006;155:729-736. 
 
(8)  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;41:401-407. 
 
(9)  Boehncke WH, Boehncke S, Tobin AM, Kirby B. The 'psoriatic march': a concept of how 
severe psoriasis may drive cardiovascular comorbidity. Experimental Dermatology 
2011;20:303-307. 
 (10)  Zanni GR. Psoriasis: issues far more serious than cosmetic. Consult Pharm 2012;27:86. 
 (11)  Fleming C, Ganslandt C, Guenther L 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 randomised, parallel group, double-blind, exploratory 
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 (12)  Kaufmann R, Bibby AJ, Bissonnette R et al. A new calcipotriol/betamethasone 
dipropionate formulation (Daivobet) is an effective once-daily treatment for psoriasis 
vulgaris. Dermatology 2002;205:389-393. 
 
 

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 (13)  Lebwohl M, Tyring S, Bukhalo M 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;9:34-41. 
 (14)  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;81:153-164. 
 (15)  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;113:439-444. 
 (16)  Norsgaard H, Kurdykowski S, Descargues P et al. Calcipotriol counteracts 
betamethasone-induced decrease in extracellular matrix components related to skin 
atrophy. Arch Dermatol Res 2014;306:719-729. 
 (17)  Menter A, Korman NJ, Elmets CA 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;60:643-659. 
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psoriasis: summary of NICE guidance. BMJ 2012;345:e6712. 
 (19)  Dauden E, Bewley A, Lambert J, Girolomoni G, Cambazard F, Reich K. Expert 
recommendations: the use of the fixed combination calcipotriol and betamethasone 
dipropionate gel for the topical treatment of psoriasis. J Eur Acad Dermatol Venereol 
2014;28 Suppl 2:22-32. 
 (20)  Hendriks AG, Keijsers RR, de Jong EM, Seyger MM, van de Kerkhof PC. Efficacy and 
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systematic literature review. J Eur Acad Dermatol Venereol 2013;27:931-951. 
 (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;151:895-897. 
 (23)  FDA. Taclonex Topical Suspension Prescribing Information.  2017.  
 
 http://www.taclonex.com/pdf/Taclonex_topical_USPI.pdf 
 (24)  Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) - simple practical measure 
for routine clinical use. Clin Exp Dermatol 1994;19:210-216. 

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 (25)  Rabin R, de CF. EQ-5D: a measure of health status from the EuroQol Group. Ann Med 
2001;33:337-343. 
 (26)  MC2 Therapeutics. Investigational Brochure MC2-01 cream, version 3, 2017 or most 
current version.  
 
 (27)  FDA. Non-Inferiority Clinical Trials to Establish Effectiveness.  2017.  
 
 (28)  Menter A, Gold LS, Bukhalo M 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. J Drugs Dermatol 2013;12:92-98. 
 (29)  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;222:148-156. 
 (30)  Wiens BL, Dmitrienko A. The fallback procedure for evaluating a single family of 
hypotheses. J Biopharm Stat 2005;15:929-942. 
 
 

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17.0 
APPENDICES 
 
Appendix 1: Contact List of MC2, Protocol Authors, Vendors, and International 
Coordinating Investigator 
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 
Linda Stein Gold, MD, International Coordinating Investigator 
Barbara Liptak, Medical Writer, Novella 
Knud Kragballe, MD, Medical Advisor 
Birgitte Vestbjerg, Director Clinical Operation, MC2 Therapeutics 
Jin Wei, Manager, Clinical Biostatistics Dermatology Division, Novella 
International Coordinating Investigator 
 
Linda Stein Gold, MD 
Henry Ford Medical Center – New Center One 
Department of Dermatology 
3031 West Grand Boulevard, Suite 800 
Detroit, MI 48202 
 
 
 

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Appendix 2: Vendors 
 
Novella Clinical, a Quintiles Company, 365 W. Passaic St, Suite 550, Rochelle Park, NJ 07662, 
United States. Novella Clinical will be responsible for all services related protocol writing and 
the conduct of the trial, as specified in the contract. 
 
ACM Global Central Laboratory, 160 Elmgrove Park Rochester, New York. ACM will be 
responsible for all services related to central laboratory analysis, as specified in the contract. 
 
Clinical Materials Services Unit (CMSU), 77 Ridgeland Rd. Rochester, NY, United States.  
CMSU will be responsible for all services related to packaging, labeling, distribution and 
destruction of the investigational medical products, as specified in the contract. 
 
United BioSource Corporation (UBC), Chemin des Coquelicots 16, CH-1214 Vernier Geneva, 
Switzerland. UBC will be responsible for services related to SAE reporting and tracking, as 
specified in the contract. 
 
DSG Inc, 325 Technology Drive, Malvern, Pennsylvania 19355, United States. DSG will be 
responsible for providing electronic data capture and IWRS services as specified in the contract. 
 
BioTelemetry Research, One Preserve Parkway, Suite 600, Rockville, Maryland 20852, United 
States. BioTelemetry Research will be responsible for the ECG services as specified in the 
contract. 
 
 
 
 
 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Approval Form 
 
Protocol MC2-01-C2  
 
 
CLINICAL TRIAL PROTOCOL APPROVAL FORM  
Product: MC2-01 (calcipotriene/betamethasone dipropionate) Cream 
Protocol number: MC2-01-C2 
Protocol title: 
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  
Version: 3.0 
Date: 27 February 2018 
 
The following person has approved this clinical trial protocol: 
 
Carol Udell 
Senior Director, Clinical Data 
Management and Biostatistics 
Novella                                              _________________________________________   
                                                                                            Signature and date 
 
 
01-Mar-2018 | 08:07:51