Clinical trial NCT03308799
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics
Start date: 2017-10-03; Completion date: 2018-06-08
Enrollment: 794 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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

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

Arms: arm 1: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) cream. One application daily for 8 weeks arm 2: Calcipotriene/betamethasone (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%). One application daily for 8 weeks. arm 3: One application daily for 8 weeks.
Interventions: intervention 1: MC2-01 cream intervention 2: Cal/BDP combination intervention 3: Cream vehicle
Intervention descriptions: intervention 1: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) cream intervention 2: calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064% intervention 3: Vehicle Cream

Protocol documents:
Prot_000.pdf: 
MC2 Therapeutics 
Clinical Trial Protocol 
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 
 
- 2 - 
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 
 
- 4 - 
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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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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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 


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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. 


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Clinical Trial Protocol 
Protocol MC2-01-C2  
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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 
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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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• 
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 
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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.  


MC2 Therapeutics 
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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. 


MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
- 61 - 
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.  
 
 


MC2 Therapeutics 
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27 February 2018 
 
- 62 - 
16.0 
REFERENCE LIST 
 
(1)  Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed 
psoriasis in US adults: results from NHANES 2003-2004. J Am Acad Dermatol 
2009;60:218-224. 
 
(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 
study. Eur J Dermatol 2010;20:465-471. 
 (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. 
 
 


MC2 Therapeutics 
Clinical Trial Protocol 
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27 February 2018 
 
- 63 - 
 (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. 
 (18)  Samarasekera E, Sawyer L, Parnham J, Smith CH. Assessment and management of 
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 
safety of combinations of first-line topical treatments in chronic plaque psoriasis: a 
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. 


MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C2  
27 February 2018 
 
- 64 - 
 (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 

SAP_001.pdf: 
MC2 Therapeutics  
                            Page 1 of 28 
Protocol No. MC2-01-C2 
 
     
 
 
                  
               05 July 2018 
Novella No. NYA13480 
 
Protocol No. MC2-01-C2 
Novella Study No. NYA13480 
 
STATISTICAL ANALYSIS PLAN 
 
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 
 
Novella Clinical 
365 West Passaic Street 
Rochelle Park, NJ 07662, USA 
 
05 July 2018 
  Johan Selmer, MD 
VP Medical Affairs 
MC2 Therapeutics 
 
Signature  
 Date 
    Carol Udell, MS 
Sr. Director, Clinical Reporting 
Novella Clinical 
Signature  
 Date 
 


MC2 Therapeutics  
                            Page 2 of 28 
Protocol No. MC2-01-C2 
 
     
 
 
                  
               05 July 2018 
Novella No. NYA13480 
Table of Contents 
Table of Contents ...........................................................................................................................2 
List of Abbreviations and Definitions of Terms ..........................................................................4 
1. 
INTRODUCTION ..................................................................................................................6 
2. 
STUDY OBJECTIVES ..........................................................................................................6 
3. 
STUDY DESIGN ....................................................................................................................6 
4. 
HARDWARE AND SOFTWARE ........................................................................................7 
5. 
DATABASE CLOSURE .......................................................................................................7 
6. 
SAMPLE SIZE DETERMINATION ...................................................................................7 
7. 
ANALYSIS POPULATION ..................................................................................................9 
8. 
HANDLING OF MISSING DATA ....................................................................................11 
9. 
DATA CONVENTIONS FOR ANALYSIS .......................................................................12 
9.1 General Statistical Principles ..............................................................................................12 
9.2 Study Day ..............................................................................................................................13 
9.3 Baseline, Change from Baseline and Reduction from Baseline .......................................13 
9.4 Analysis Visit Windows .......................................................................................................13 
9.5 Analysis Sites ........................................................................................................................14 
9.6 Multiple Comparisons .........................................................................................................14 
10. STATISTICAL EVALUATION .........................................................................................15 
10.1 Subject Disposition ...............................................................................................................15 
10.3 Protocol Deviation ................................................................................................................15 
10.4 Demographic and Baseline Characteristics .......................................................................16 
10.5 Visit Compliance ..................................................................................................................16 
10.6 Study Medication Exposure and Compliance ...................................................................16 
10.7 Prior and Concomitant Medications ..................................................................................17 
10.8 Medical/Surgical History .....................................................................................................18 
10.9 Efficacy Analysis ..................................................................................................................18 
10.9.1 
Primary Efficacy Endpoint .......................................................................................18 
10.9.2 
Secondary Efficacy Analyses ....................................................................................19 
10.9.3 
Other Endpoints .........................................................................................................22 
10.9.4 
Investigator’s Assessment of the Body Surface Area Involvement (BSA)............24 
10.10 
Safety Analysis ...........................................................................................................24 


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               05 July 2018 
Novella No. NYA13480 
10.10.1 
Adverse Events ...........................................................................................................25 
10.10.2 
Investigator Assessed Local Skin Reaction .............................................................26 
10.10.3 
Subject Assessed Local Skin Reaction .....................................................................26 
10.10.4 
Safety Laboratory Parameters .................................................................................26 
10.10.5 
Vital Signs ...................................................................................................................27 
10.10.6 
Standard 12-lead electrocardiogram (ECG) ...........................................................27 
10.10.7 
Physical Examination (PE)........................................................................................27 
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES .........................27 
12. HEADINGS ..........................................................................................................................27 
13. ARCHIVING AND RETENTION OF DOCUMENTS ....................................................28 
14. REFERENCE .......................................................................................................................28 
15. OUTLINE OF PROPOSED TABLES, LISTINGS AND FIGURES ..............................28 
 
 
 
 
 
 
 
 
 
 
 
 


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               05 July 2018 
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List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
AE 
Adverse event 
ADaM 
Analysis data model 
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 
DLQI 
Dermatology Life Quality Index  
ECG 
Electrocardiogram 
EQ-5D 
EuroQOL five dimensions questionnaire 
EQ-VAS 
EQ-5D visual analog scale 
IP 
Investigational product 
IRB 
Institutional Review Board 
ITT 
Intent to treat 
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 
ODS  
SAS Output Delivery System 
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 
PT 
Preferred Term 
QOL 
Quality of Life 
RTF 
Rich-text-formatted 


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Abbreviation 
Definition 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard deviation 
SDTM 
Study data tabulation model 
SE 
Standard error 
SGA 
Subject’s global assessment 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment emergent adverse event 
TESAE 
Treatment emergent serious adverse event 
TC 
Telephone call 
UPT 
Urine pregnancy test 
 


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Protocol No. MC2-01-C2 
 
     
 
 
                  
               05 July 2018 
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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the study Protocol version 3.0 dated February 27, 
2018.  
This document provides additional details concerning the statistical analyses outlined in the 
protocol and reflects any changes to the protocol from any amendments. This plan will not repeat 
all the definitions given in the protocol but will provide further details of the summaries and 
analyses planned therein.  
Additional analyses will be made as part of the validation of the Psoriasis Treatment Convenience 
Scale. These analyses will be described and reported separately.  
2. STUDY 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.  
3. STUDY DESIGN 
This is a Phase 3, 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. 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.  
A total of 791 subjects are planned to be enrolled in order to have approximately 712 completed 
subjects. Qualified subjects will be randomised into MC2-01 cream, MC2-01 cream vehicle and 
active comparator in a 3:1:3 ratio stratifying by site and baseline severity. Subjects are healthy 
males or non-pregnant females, at least 18 years of age, with a clinical diagnosis of plaque psoriasis 
(psoriasis vulgaris) of at least 6 months duration that involves non-scalp regions of the body (trunk 
and/or limbs), with a PGA of disease severity of mild or moderate on the body (trunk and/or limbs) 
and a minimum modified Psoriasis Area and Severity Index (mPASI) score of at least 2 in at least 
one body region (i.e., psoriasis affecting at least 10% of trunk and/or limbs). 
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. The study will include a total of 8 scheduled 
visits: a screening visit, a baseline visit, four on treatment visits (Visit 3 telephone call), end of 


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Protocol No. MC2-01-C2 
 
     
 
 
                  
               05 July 2018 
Novella No. NYA13480 
treatment visit, and a follow-up visit. Unscheduled visits 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 will be recorded in the subject’s records. 
During the treatment period, the investigator will score the disease severity of the subject using 
the PGA, modified Psoriasis Area and Severity Index (mPASI) 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), 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.  
4. HARDWARE AND SOFTWARE 
Statistical analysis will be performed following Novella Clinical standard operating procedures 
(SOP) and on the Novella Clinical computer network. All statistical analysis will be performed 
using SAS Version 9.3 or higher with program code prepared specifically for the project by 
qualified Novella Clinical statisticians and SAS programmers. 
The SAS programs will generate rich-text-formatted (RTF) output with the “RTF” extension using 
the SAS Output Delivery System (ODS). The summary tables and listings will be formatted using 
the Times New Roman 9-point font. The RTF output is included in report documents prepared 
with Microsoft Word and converted to PDF format without typographical change. 
Datasets will be created and taken as input to validated SAS programs to generate the report-ready 
tables, listings, and figures. Each output display will show the names of the data sets and SAS 
program used to produce it. 
5. DATABASE CLOSURE 
After completion of all data review procedures, validation of the project database, and approval of 
the data review document by the study sponsor, the clinical database will be closed. Any change 
to the clinical database after this time will require written authorization, with explanation, by the 
Sponsor and the Biostatistician. 
6. SAMPLE SIZE DETERMINATION 
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:  


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Protocol No. MC2-01-C2 
 
     
 
 
                  
               05 July 2018 
Novella No. NYA13480 
The non-inferiority margin was determined according to the draft Food and Drug Administration 
(FDA)-Guidance for Industry: Non-inferiority Clinical Trials as a fixed margin.  
A summary of responders, based on the PGA, at Week 8 from three randomised trials of 
calcipotriene and betamethasone dipropionate gel is shown below to help determine the statistical 
margin M1 and the clinical margin M2. The clinical margin M2 is used in the determination of 
sample size. 
Table 1. Determination of sample size 
 
Daivobet 
Vehicle 
Daivobet – Vehicle 
Trial 
N 
PGA 
success % 
N 
PGA 
success 
% 
% 
99% CI 
Menter et al, 2013   
482 
29.0 
95 
6.3 
22.7 
(14.4, 31.1) 
Langley et al, 2011 
183 
39.9 
91 
5.5 
34.4 
(23.2, 45.6) 
Fleming et al, 2010 
162 
27.2 
40 
0 
27.2 
(18.2, 36.2) 
 
Total  
 
 
 
 
26.2 
(19.9, 32.6) 
The 
lower 
99%-confidence 
limit 
of 
the 
difference 
in 
response 
rate 
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.  
Assumption’s 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 favour 
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.  


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Protocol No. MC2-01-C2 
 
     
 
 
                  
               05 July 2018 
Novella No. NYA13480 
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. 
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).  
Therefore a total enrolment of approximately 791 subjects is planned to have approximately 712 
completed subjects. 
7. ANALYSIS POPULATION 
Three analysis populations will be defined for analysis: 
• Intent-To-Treat (ITT) population: will include all subjects who were randomised and 
dispensed the trial medication at Randomisation. Subjects who return all the trial 
medication unused will be excluded. 
• 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. 
• 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; 
• Usage of restricted medications/treatments; I.e. medications/treatments that  
according to medical judgement may impact the primary endpoint analysis; 
• Nonadherence to the visit schedule at Week 8 ± 7days; 
• 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 Week 4 to Week 8;  
• 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; 
In particular, subject treatment days that are approved by the investigator for study 
drug stoppage due to clear skin, i.e., those marked as N/A in subject diary, will be 
included in the computation of compliance as if subjects were compliant these days.   


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• Safety Population: will include all subjects who were randomised and dispensed the trial 
medication at Randomisation. Subjects who return all the trial medication unused will be 
excluded.  
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 
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.  
All efficacy analyses will be conducted according to the randomised treatment assignment; all 
safety analyses will be conducted according to the treatment actually received.  
8. ESTIMANDS 
When analyzing the confirmatory endpoints aiming to demonstrate superiority, the primary 
analysis will be focusing on a treatment-policy estimand. An additional hypothetical-strategy 
estimand will be used to assess external validity for the primary and the key secondary endpoint. 
The primary analyses of non-inferiority will be made based on the PP-population, using only 
observed cases. To assess external validity, also the analysis of non-inferiority will be made 
based on the two estimands, treatment-policy and hypothetical-strategy. They are described in 
further detail below.  
Treatment-policy estimand: the effect of initiating the treatment regimen in subjects with mild-
to-moderate psoriasis, with or without any other psoriasis treatment, and whether or not the 
subject adhered to the treatment regimen.   
Thus, for the treatment-policy estimand all available data will be used. Missing data will be 
imputed  
Hypothetical-strategy estimand: the expected effect in subjects with mild-to-moderate psoriasis if 
all subjects adhered to the treatment regimen and did not take any other treatment that according 
to medical judgement may impact the primary efficacy endpoint.  
This is interpreted in the sense that subjects did not initiate other treatment that according to 
medical judgement may improve psoriasis, and for visits after baseline adhered to the treatment 
schedule defined as application of IP as specified by the investigator at the previous site visit for 
at least 70% of the days from the Baseline visit to Week 4, Week 4 to Week 6 and Week 6 to 
Week 8. For example, applying IP for 10 out of 14 days between Week 4 and Week 6 is 
considered adherence, while 9 out of 14 days is not. Computations to determine adherence are 


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done using actual visit dates and compliance data from the compliance page in the CRF.  For the 
hypothetical-strategy estimand, only data at or prior to use of other treatment that may improve 
psoriasis according to medical judgement, and prior to non-adherence to treatment schedule is 
used. Missing data, data after use of other psoriasis treatment, and data after non-adherence is 
imputed. 
In addition, estimands corresponding to a composite-strategy estimand and a while-on-treatment 
estimand will also be applied.   
9. HANDLING OF MISSING DATA  
For superiority analyses based on the ITT set, a variety of methods will be used to impute missing 
data, 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 and sensitivity analyses using LOCF, BOCF and NRI will be performed to 
assess the robustness of imputation assumptions. The primary non-inferiority evaluation will be 
on the PP population using an Observed Cases (OC) analysis, i.e., there will be no imputation for 
missing data at any time point.  
The imputation procedures for post-baseline missing data are described below. 
• MI: Multiple imputations is a simulation based approach where missing values are replaced 
by multiple Bayesian draws from the conditional distribution of missing data given the 
observed data and covariates, creating multiple completed data sets. These completed 
datasets can then be analysed using standard analysis methods. Rubin (1987) presented 
rules for how to combine the multiple sets of estimates to produce overall estimates, 
confidence intervals, and tests that adequately incorporate missing data uncertainty.  
Missing values for PGA data will be imputed using the SAS MI procedure. Intermittent 
missing values of PGA will be imputed separately for each treatment group using the 
Markov Chain Monte Carlo (MCMC) method. 100 copies of the dataset with monotonic 
missing pattern will be generated. Assuming normality for the PGA score is motivated by 
Schaefer (1997), where it was shown that the multivariate normal approximation for the 
imputation of incomplete categorical and binary data is robust. 
For each of the 100 datasets, missing values at scheduled visits will then be imputed 
separately for each treatment group using a monotone regression method that includes: 
prior systemic biologic use for psoriasis (yes/no) and baseline PGA severity 
(mild/moderate) as categorical variables; duration (years) of psoriasis (calculated as year 
of baseline minus year of first psoriasis diagnosis) and PGA scores at weeks 1, 4, 6, and 8 
as continuous variables.  


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The primary efficacy endpoint will be calculated from these imputed datasets. Note that 
imputed PGA scores can take fractional values (eg, 1.4, 2.2, etc.). In order to account for 
this, PGA score will be rounded to the nearest positive integer number and negative values 
will assume to be 0. PGA Treatment Success status (Yes/No) will then be derived based 
on the imputed datasets.  
Missing values for secondary efficacy endpoints, mPASI and itch by numerical rating scale 
(NRS), will be imputed by MI using similar method as described above for the primary 
efficacy endpoint, with replacement of PGA by each respective endpoint in the imputation 
models.  
A pre-specified seed number of 213213 will be used in all imputation procedures as 
described above. 
This method will be used to impute missing data corresponding to the treatment-policy 
estimand as well as the hypothetical-strategy estimand.  
• LOCF: The last observed value will be carried forward for any subsequent missing values. 
Baseline values will not be carried forward.   
• BOCF: The baseline value will be used for any missing post-baseline values. 
• NRI: Any missing value will be assumed to be a ‘non-responder’ with respect to the 
given analysis variable. This method corresponds to a composite strategy estimand. 
• Imputation of missing or invalid Psoriasis Treatment Convenience Scale (PTCS) score 
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 
‘PCTS while on treatment’ estimand. 
10. DATA CONVENTIONS FOR ANALYSIS 
9.1 General Statistical Principles 
All statistical processing will be performed using the SAS system (Version 9.3 or higher).  
All observed and derived variables (e.g., change from baseline) used in the summaries of analyses 
will be presented in by-treatment and by-subject listings. Descriptive statistics will be used to 


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provide an overview of the efficacy and safety results. For categorical parameters, the number and 
percentage of subjects in each category will be presented. The denominator for percentage will be 
based on the number of subjects appropriate for the purpose of analysis. For continuous 
parameters, descriptive statistics will include number of observations, mean, standard deviation 
(SD), median, Q1, Q3, and range.  
Except where noted, all statistical tests will be 2-sided and will be performed at the 0.05 level of 
significance.  
No interim analyses are planned.  
9.2 Study Day 
For purpose of the SAP, Day 1 is defined as the date of first application of study drug, which 
corresponds to Day 0 of the study protocol. Study day is calculated relative to the date of Day 1. 
9.3 Baseline, Change from Baseline and Reduction from Baseline 
Baseline is defined as the last available non-missing value prior to first application of study drug. 
Change from baseline will be defined as the post-baseline value minus the baseline value, unless 
otherwise stated. Reduction from baseline will be defined as the baseline value minus the post-
baseline value, unless otherwise stated. Percent reduction from baseline is calculated as the 
baseline value minus post-baseline value divided by the baseline value, expressed as a 
percentage, unless otherwise stated.  
9.4 Analysis Visit Windows 
Efficacy and safety endpoints will be analysed according to their windowed visits defined by actual 
study day. If more than one valid evaluation occurs within a single visit window, then the analysis 
will take the one closest to the target day. If the two visits are equidistant from the target day, the 
later will be used. In particular, for safety assessments with repeats, the scheduled (non-repeat) 
values will be included for summary.  
 The following analysis visit windows will apply: 
Visit 
Week 
Target Day 
Assessment Window 
2 
1 
8 
Post-dose – Day 11 
4 
4 
29 
23 — 36 
5 
6 
43 
37 — 50 
6 
8 
57 
51 — 64 
7 (Follow-up) 
10 
71 
Nominal (Post last-dose) 


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9.5 Analysis Sites 
There will be approximately 57 trial sites in the United States. The goal is to randomise at least 14 
subjects at each site. Sites that do not randomise at least 14 subjects 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. Statistical test investigating the statistical 
homogeneity of the primary outcome across “analysis sites” will be performed. Further detail is 
provided in section 10.9.1. 
9.6 Multiple Comparisons 
The global Type-I error for the secondary endpoints 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 PTCS at Week 8 between MC2-01 cream and active 
comparator will be tested in a hierarchical way with a loop back procedure with initial error 
probability weights 2/3 for H1 (change from baseline in 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 such that the global Type-I error does not exceed 5%.  
3. If both non-inferiority of MC2-01 to active comparator with respect to percentage 
reduction from Baseline in mPASI and superiority of MC2-01 vs. active comparator with 
respect to PTCS 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 NRS from baseline to Week 4 
(in the subgroup of subjects with an NRS score ≥ 4 at baseline) 
The testing strategy for the secondary endpoints is illustrated below in the case where the primary 
null-hypotheses have been rejected. If superiority/non-inferiority is demonstrated for one of the 
secondary endpoints, the corresponding unspent α-level will be reallocated according to the 
direction of the edges.  
 


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10.  STATISTICAL EVALUATION  
10.1 Subject Disposition 
The number and percentage of subjects who were screened, randomised, included in each analysis 
population, completed the study, discontinued from the study (overall and by reason for 
discontinuation), and who were excluded from the PP population (overall and by reason for 
exclusion) will be summarized, overall, by treatment group and by sites.  
A by-subject enrolment and disposition listing will be presented for all randomised subjects. 
Subjects who are screen failures and subjects who are not randomised will also be presented in a 
separate listing. 
10.3 Protocol Deviation 
Protocol deviations will be presented in a by-subject listing. 
mPASI  
Comparator Superior 
to Vehicle 
αlocal=0.0333 
mPASI 
MC2-01 Non-inferior to Comparator 
αlocal=0.0333 
PTCS 
MC2-01 Superior to 
Comparator  
αlocal=0.0167 
 Itch IRS 
MC2-01 Superior to Vehicle αlocal=0.05 
Itch 4-point Improvement 
MC2-01 Superior to Vehicle αlocal=0.05 
mPASI  
MC2-01 Superior to 
Vehicle 
αlocal=0.0333 
Alpha Reallocated 


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10.4 Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarized overall and by treatment for the 
ITT, PP, and Safety populations. The following demographic and baseline variables will be 
included: 
• Age (years) 
• Sex 
• Race  
• Ethnicity  
• Fitzpatrick Skin Type 
• Height (cm) 
• Weight (kg) 
• BMI (kg/m2) 
• Baseline PGA (Trunk and/or Limbs) 
• Baseline mPASI (Trunk and/or Limbs)  
• Baseline SGA 
• Duration of psoriasis in years (calculated as year of baseline minus year of first psoriasis 
diagnosis) 
• Prior systemic biologic use for psoriasis (yes/no) 
10.5 Visit Compliance 
A by-subject visit list will be provided for all randomised subjects. 
10.6 Study Medication Exposure and Compliance 
Subjects will record the date of each trial medication application in the subject diary. The kit 
number, and corresponding date dispensed and returned will be collected. The weight of the 
returned kits will also be collected.   
The following parameters of study medication exposure will be summarized by treatment group 
for the ITT and PP Population: 
• Total number of days of exposure to the study drug, defined as the date of last application 
of study drug minus date of first application plus one 
• Total number of missed doses collected in eCRF 


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• Total number of doses applied, defined as the total number of doses required minus total 
number of doses missed. Total number of doses required is defined as total number of days 
of exposure minus any days of investigator approved stop (if applicable) 
• Total amount of drug used (g), defined as the summation of amount of drug used per kit 
for all dispensed kits. Amount of drug used per kit is defined as the difference in weight 
between the returned and dispensed kits, where weight of dispensed kits is a unit value. 
Amount of drug used for sealed and unreturned kits will be assumed to be 0.0 g. 
• Amount of drug used per week (g/per week), defined as the total amount of drug used 
divided by total number of days of exposure to the study drug multiplied by 7. 
• Percentage of compliance in each of the 2 periods (from Day 1 to Week 8 and from Week 
4 to Week 8), defined as (the total number of doses applied in the given period + number 
of days where no dose is to be taken due to clear skin as agreed with the investigator in the 
given period) divided by total days of exposure of each period. Total days of exposure is 
calculated as last dose date – first dose date + 1 for Day 1 to Week 8; and last dose date – 
Week 4 visit date + 1 for Week 4 to Week 8 period. If Week 4 visit is missing, the duration 
of exposure is calculated as total days of exposure from Day 1 to Week 8 – 29.  
• Subject compliance (Yes, No), defined as at least 80% in percentage compliance from 
Week 4 to Week 8 and from Day 1 to Week 8  
10.7 Prior and Concomitant Medications 
Prior (with stop dates prior to Day 1) and concomitant medications (ongoing or with stop dates on 
or after Day 1) for all randomised subjects will be provided in a by-subject listing. Prior and 
concomitant medications will be summarized by WHO-DDE Anatomical-Therapeutic-Chemical 
(ATC) classification and preferred term (PT) for each treatment and overall for all randomised 
subjects. 
For the determination of prior vs. concomitant medications, the following rules regarding the stop 
date will be applied: 
• If only year was recorded, and it is before Day 1, it is a prior medication; if year is same or 
after Day 1, it is assumed to be a concomitant medication. 
• If day is missing, but month and year are before Day 1, it is a prior medication; if month 
and year are the same or after Day 1, it is assumed to be a concomitant medication. 
• If start date is after Day 1, it is a concomitant medication regardless. 
Psoriasis treatment history will be summarized by frequency counts and percentages, and a by-
subject listing. 


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10.8 Medical/Surgical History 
Past and current medical conditions will be coded using MedDRA dictionary and summarized by 
System Organ Class (SOC) and PT for PP and ITT. Medical history for all randomised subjects 
will be provided in a by-subject listing. 
10.9 Efficacy Analysis 
10.9.1 Primary Efficacy 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. 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.  
Superiority analysis: 
The  superiority evaluation will be based on the ITT population using MI.  
The PGA response rate for MC2-01 cream and active comparator at Week 8 will first be compared 
to MC2-01 cream vehicle at Week 8 for a superiority evaluation using the treatment-policy 
estimand for the ITT population and imputing missing data using multiple imputation.  
The analysis will be done using a logistic model with treatment, baseline PGA severity 
(mild/moderate) and analysis site as independent variables. Superiority will be tested at the 5% 
significance level (p<0.05; two-sided). The estimate and standard error of the log odds ratio will 
be evaluated for each of the multiple imputed datasets and combined in PROC MIANALYZE.  
Sensitivity analyses:  
Internal validity: 
• The primary analysis using the treatment-policy estimand is repeated for the ITT 
population using LOCF, BOCF, and NRI respectively. 
External validity: 
• The primary analysis is repeated using the hypothetical-strategy estimand based on the ITT 
population and imputing missing data using MI.  
• OC analysis based on the PP population. 
Non-inferiority (NI) analysis: 
If and only if superiority to MC2-01 cream vehicle for both MC2-01 cream and for active 
comparator is claimed at the 5% significance level, MC2-01 cream will be compared to active 
comparator for a non-inferiority evaluation on the PP-population using OC analysis. 


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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 success will be calculated along with its 
95% confidence interval (CI) using normal approximation. A 95%, 2-sided CI for PM-PA, where 
PM and PA is the PGA treatment success rate at Week 8 for MC2-01 cream and active comparator 
respectively, will be computed using normal approximation using Proc FREQ with RISKDIFF 
option. MC2-01 will be considered non-inferior to active comparator if the lower bound of the 2-
sided 95% CI is ≥ -10% points. 
Sensitivity analyses: 
• The primary analysis is repeated using the hypothetical-strategy estimand based on the ITT 
population and imputing missing data using MI.  
The primary analysis is repeated using the treatment-policy estimand for the ITT population using 
MI, LOCF, BOCF, and NRI respectively. 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 combined by applying Rubin’s rules in PROC MIANALYZE and the 
95% CI of the difference will be computed.  
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. Analysis 
sites with outlying results will be investigated and sensitivity analysis excluding outliers may be 
performed if deemed necessary.  
10.9.2 Secondary Efficacy Analyses 
Secondary endpoints are the following:  
• Percentage reduction from Baseline in the mPASI score at Week 8, defined as Baseline 
score minus Week 8 score divided by Baseline score.  
• Subject assessment of treatment convenience at Week 8 using the PTCS between MC2-01 
cream and active comparator; PTCS 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? 


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6. Overall, how satisfied were you with the medical treatment? 
The PTCS score calculated as the sum of the first 5 questions will be used for purpose of 
the secondary endpoint analysis. Question number 6 will not contribute to the PTCS score 
but will be included in the validation of the PTCS 
• 
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) 
• Percentage of subjects with four-point improvement on the itch by NRS from baseline to 
Week 4 (MC2-01 cream vs MC2-01 cream vehicle). The endpoint will be analyzed in the 
subgroup of subjects with Itch (assessed by NRS) ≥ 4 at baseline. 
The secondary efficacy endpoint analyses will be based on the PP population and ITT population. 
For the analysis of non-inferiority, the primary population will be the PP-population and the 
analysis will be based on an OC analysis. For the analyses of superiority, the primary population 
will be the ITT population, using imputation methods as described in Section 8 above.  
Secondary endpoints will only be tested if the primary endpoint rejects the null-hypothesis.  
Percentage reduction from Baseline in mPASI score at Week 8 
The analyses are done in analogy with those of the primary endpoint.  
Superiority analysis: 
The percent reduction in mPASI score at Week 8 of MC2-01 cream and active comparator will 
first be compared with that of MC2-01 cream vehicle for a superiority evaluation using the 
treatment-policy estimand for the ITT population and imputing missing data using multiple 
imputations. Superiority will be assessed using an analysis of covariance (ANCOVA) model with 
treatment, baseline PGA severity (mild/moderate), baseline mPASI and analysis site as 
independent variables.  
Internal validity: 
• The primary analysis using the treatment-policy estimand is repeated for the ITT 
population using LOCF and BOCF respectively. 
External validity: 
• The primary analysis is repeated using the hypothetical-strategy estimand based on the ITT 
population and imputing missing data using MI.  
• OC analysis based on the PP population. 
Non-inferiority (NI) analysis: 


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If and only if superiority to MC2-01 cream vehicle for both MC2-01 cream and for active 
comparator can be claimed at the significance level determined by the loop-back procedure 
described in section 9.6 above, the NI analysis of the mPASI will be conducted.  
The primary analysis of NI will be based on the PP-population with an OC analysis using a similar 
ANCOVA model. A lower confidence limit will be calculated for the difference in mean 
percentage reduction (MC2-01 cream – active control), using the LSMEANS function. The alpha 
level corresponding to the confidence interval will be determined by the loop-back procedure 
described above. Non-inferiority will be claimed if the lower limit of the CI is ≥ −10%. 
Sensitivity analyses: 
• The primary analysis is repeated using the hypothetical-strategy estimand based on the ITT 
population and imputing missing data using MI.  
• The primary analysis is repeated using the treatment-policy estimand for the ITT 
population using MI, LOCF, and BOCF respectively. 
Subject assessment of treatment convenience at Week 8  
Superiority between MC2-01 cream and active comparator will be assessed by using an ANOVA 
model with treatment, baseline PGA severity (mild/moderate), and analysis site as independent 
variables. The primary analysis will be based on the ITT population, where missing and invalid 
PTCS scores are imputed using the last valid measure prior to the visit corresponding to a PTCS 
while-on-treatment estimand.   
Superiority will be claimed if the lower limit of the CI, derived from the difference (MC2-01 cream 
– active comparator) in LSMEANS, is >0. The alpha level corresponding to the CI will be 
determined by the loop-back procedure. 
Change in Itch by NRS from baseline to Week 4  
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 
imputation methods as described in Section 8 above.   
Percentage of subjects with 4-point improvement in NRS from baseline to Week 4   
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. The primary analysis will be based on the subgroup of the 
ITT population with baseline itch ≥ 4, using imputation methods as described in Section 8 above. 
 
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 


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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. 
10.9.3 Other Endpoints  
Analyses of the other endpoints will primarily be based on the PP population using an OC 
approach. Supportive analyses will be made based on the ITT population; OC approach will be 
used for all patient reported outcomes; MI will be used for efficacy endpoints based on the ITT 
population. 
Efficacy  
• PGA success rate at Week 4;  
• Percentage reduction from Baseline in the mPASI score at Week 4;  
• Percentage of subjects with PASI 50 (at least 50% reduction in mPASI from Baseline) at 
Week 4 and Week 8;  
• Percentage of subjects with PASI 75 (at least 75% reduction in mPASI from Baseline) at 
Week 4 and Week 8.  
• Reduction from Baseline in SGA at Week 4 and Week 8;  
Patient reported outcomes  
• Change in total DLQI score at Week 4 and Week 8 from baseline; The DLQI will be scored 
according to the developer instructions. The scoring of each question is as follows:  
Response 
Score 
Very much 
scored 3 
A lot 
scored 2 
A little 
scored 1 
Not at all 
scored 0 
Not relevant 
scored 0 
Question unanswered 
scored 0 
Question 7: “prevented work or studying” 
scored 3 
 
The DLQI will also be summarized by the following domains: symptoms and feelings, 
daily activities, leisure, work and school, personal relationships, and treatment.  


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The scoring of DLQI will follow the developer’s manual1. Specifically:  
o If one question is left unanswered this is scored 0 and the scores are summed and 
expressed as usual out of a maximum of 30. 
o If two or more questions are left unanswered the questionnaire is not scored. 
o If question 7 is answered ‘yes’ this is scored 3. If question 7 is answered ‘no’ but 
then either ‘a lot’ or ‘a little’ is ticked this is then scored 2 or 1. If “Not relevant” is 
ticked, the score for Question 7 is 0. If it is answered ‘no’, but the second half is 
left incomplete, the score will remain 0. 
o If two or more response options are ticked, the response option with the highest 
score should be recorded. 
o If there is a response between two tick boxes, the lower of the two score options 
should be recorded. 
o The DLQI can be analysed by calculating the score for each of its six sub-scales 
(see above). When using sub-scales, if the answer to one question in a sub-scale is 
missing, that sub-scale should not be scored. 
• Change in EQ-5D score at Week 4 and Week 8 from baseline. The EQ-5D consists of a 
descriptive system (based on the five first questions) and a VAS scale (How good or bad 
is your health today: Range of 0 (worst health) to 100 (best health)). Change from baseline 
in EQ-5D will be described using the below endpoints 
• Change in EQ-5D VAS from baseline. The score of the VAS scale is the answer 
from 0 to 100. From this the change from baseline is derived.  
• Change from baseline based on the descriptive system. Each of the five questions 
have 5 reply options. Level ‘1’ (No bother) is coded as ‘1’, level ‘2’ as ‘2’ and so 
forth. Hence, after scoring each patient will have a health state consisting of 5 digits 
e.g. ´13425’ at each visit. A post-baseline assessment is characterised according to 
whether there is “No change/improved health/worse health/’mixed’ change” 
compared to baseline. Here, an EQ-5D health state is better if it is better on at least 
one other dimension and no worse in any other dimension. And a health state is 
worse than another if it is worse in at least one dimension and no better in any other 
dimension. 
                                                          
1 DLQI Instructions for use and scoring. A Y Finlay, G K Khan April 1992. Available at: 
http://sites.cardiff.ac.uk/dermatology/quality-of-life/dermatology-quality-of-life-index-dlqi/dlqi-
instructions-for-use-and-scoring/ 
 


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• Change from baseline in EQ-5D index value. The descriptive health states 
described above will be transformed into an index value by use of the UK crosswalk 
value set. 
• Change in itch intensity assessed on a numerical rating scale (Itch by NRS, 0-10) from 
baseline to Week 1 as well as from baseline to week 8 (MC2-01 cream vs MC2-01 cream 
vehicle) 
• Subject assessment of each individual question at Week 8 in the Psoriasis Treatment 
Convenience Scale  
PGA success, 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. The 
endpoints PASI 50 and PASI 75 will be summarized using frequency counts by treatment and visit. 
The endpoint 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 
analysis site as independent variable. Absolute values and absolute changes from baseline will be 
summarized using descriptive statistics for each treatment group by visit. 
The Patient reported outcomes DLQI, EQ-5D (Vas and index value), 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. Absolute 
values and absolute changes from baseline will be summarized using descriptive statistics for each 
treatment group by visit.  Change from baseline in the descriptive system of EQ-5D will be 
described using summary statistics. 
The individual questions of the PTCS will be analysed similarly to the PTCS scale. Statistical 
analyses for the other endpoints will be exploratory only and not for statistical inference. 
10.9.4 Investigator’s Assessment of the Body Surface Area Involvement 
(BSA) 
The total psoriatic involvement on the trunk and limbs (excluding genital and intertriginous areas) 
will be recorded as a percentage of the total BSA. Results will be presented in a by-treatment and 
by-subject listing. 
10.10 
Safety Analysis 
All safety analyses will be based on the Safety Population according to the treatment received. The 
safety end points are: 
• Adverse events (AEs) 
• Local Skin Reaction Assessment 


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• Laboratory parameters 
• Vital signs 
• Standard 12-lead electrocardiogram (ECG) 
• Physical examination (PE) 
10.10.1 Adverse Events 
AE terms will be coded using MedDRA dictionary. A treatment-emergent AE (TEAE) is defined 
as an AE with a start date on or after the first application to trial medication. If relationship to study 
medication is missing, the event will be conservatively summarized as being related to study drug. 
If intensity is missing, a separate category of missing intensity will be included in the summary 
table, and no imputation of severity will be performed. Through the data cleaning process, all 
attempts will be made to avoid missing values for relationship and severity. 
All AEs will be presented in a by-subject listing for all screened subjects, detailing the verbatim 
term given by the investigator, the PT, SOC, location of AE to treatment area, start date, stop date, 
intensity, outcome, relationship to study medication (definitely related, probably related, possibly 
related, and not related), action taken with study medication, action taken to treat the AE, 
seriousness and criteria for seriousness. Serious AEs will also be presented in a separate listing.  
An overall summary of AEs will be presented by treatment and overall. The summary will include 
the total number of events, frequency counts and percentages with: 
• Any AE 
• Any TEAE 
• Any serious TEAE 
• Any treatment-related TEAE  
• Any TEAE leading to study drug discontinuation 
Summaries of the incidence of TEAEs, and SAEs will be displayed by treatment according to the 
following: 
• All TEAEs by PT in descending order of frequency (the combined frequency of both 
treatments) 
• All TEAEs by SOC, PT, and maximum severity (mild, moderate, or severe) 
• All TEAEs by SOC, PT, and maximum causality (not related, related) to the study drug 
At each level of summarization, a subject will be counted once if he/she reported one or more 
events. The severity of TEAEs and relationship to study drug will be summarized in a similar 
manner. For summaries of relationship to study drug, a subject will be classified according to the 


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closest relationship. For summaries of TEAE severity, a subject will be classified according to the 
highest severity. 
10.10.2 Investigator Assessed Local Skin Reaction  
Assessments of local skin reaction will be performed at all post-screening visits for all subjects in 
the trial 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 summarized by 
visit for each of the LSR categories.  
The investigator LSR sum score will be calculated as the summation of the perilesional signs and 
lesional signs. The perilesional signs will include erthema, scaling, edema, atrpoy, vesicles and 
erosin/ulceration. The lesional signs will include vesicles and erosin/ulceration. Missing values 
will be imputed as the mean of the remaining categories of perilesional and lesional signs. If all 
categories have missing values no imputation will be made.  
For the LSR sum score, the Area under the Curve (AUC) will be calculated for each subject for 
four time intervals using the trapezoidal rule; 1) from Baseline to end of Week 1; 2) from Baseline 
to end of Week 4; and 3) from Week 4 to End of Trial/last assessment and 4) from Baseline to End 
of Trial/last assessment. These parameters will be compared between treatment groups using 
ANOVA.  
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. 
10.10.3 Subject Assessed Local Skin Reaction  
Subjects will assess burning and/or pain after application. Results will be summarized and 
presented in a by-treatment and by-subject listing. 
10.10.4 Safety Laboratory Parameters 
Clinical laboratory (serum biochemistry and urinalysis) results will be presented in a by-subject 
listing.  
Absolute values, changes from baseline, and relative changes from baseline (defined as ratio of 
the post-baseline vs baseline value) will be summarized using descriptive statistics (means, 
medians, standard deviations, ranges, and coefficient of variations) by treatment and visit. Serum 
biochemistry will include serum calcium (albumin corrected), serum albumin, serum alkaline 
phosphatase, serum phosphate, plasma parathyroid hormone and. Urinalysis parameters will 
include urinary calcium, urinary phosphate and urinary calcium:creatinine. Shift tables using 


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extended normal ranges (baseline to most extreme post-baseline value) will be summarized. Out 
of range laboratory values will be flagged.  
Serum and urine pregnancy test will be presented in a by-subject listing with subject childbearing 
potential by visit.             
10.10.5 Vital Signs 
Vital signs data will be presented in a by-treatment and by-subject listing with indication of the 
arm the vital signs were collected from for the following tests: 
• Blood pressure (mmHg) - systolic and diastolic 
• Pulse rate (beats per min) 
Absolute values and changes from baseline will be summarized using descriptive statistics by 
treatment and visit.  
10.10.6 Standard 12-lead electrocardiogram (ECG) 
A standard 12-lead electro cardiogram (ECG) will be evaluated by the Investigator or a designee 
and will be sent to a central laboratory for interpretation. Frequency counts will be used to 
summarize the ECG findings (normal, abnormal not clinically significant, abnormal clinically 
significant) by treatment and visit. Shift tables showing changes in ECG findings from baseline 
will be summarized. All results will also present in a by-subject listing. 
10.10.7 Physical Examination (PE) 
Physical examinations results will be presented in a by-subject listing.  
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES 
Not applicable. 
12. HEADINGS 
Each page of the analysis will show the sponsor’s name, the investigational product, the protocol 
and number. Report tables will be embedded in the MS Word report document from SAS program 
output without change. The footer of each table will show the name of the SAS program module 
which generated it, the names of all data sets providing input data in the program and the date and 
time the table was generated. 


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13. ARCHIVING AND RETENTION OF DOCUMENTS 
After finalization of the analysis, the following will be archived at Novella Clinical and/or with 
the study sponsor: 
• SAP and any amendments 
• All SAS code used in the project for statistical analysis, report tables generation, and 
analysis data set creation 
• Tables, listings and figures as included in the clinical study report 
• SAS study data tabulation model (SDTM) and analysis dataset model (ADaM) datasets 
14. REFERENCE 
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 study. Eur J Dermatol 
2010;20:465-471. 
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 randomised, controlled clinical trial. Dermatology 2011;222:148-156. 
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 randomised, 
double-blind, vehicle-controlled trial. J Drugs Dermatol 2013;12:92-98. 
Rubin, D.B. (1987). Multiple Imputation for Nonresponse in Surveys. New York: Wiley.  
Schaefer, J.L. (1997). Analysis of Incomplete Multivariate Data, Chapman&Hall. 
15. OUTLINE OF PROPOSED TABLES, LISTINGS AND FIGURES