A Randomised, Open-label, Maximal Use Trial, Evaluating the Pharmacokinetic Profile of Active Ingredients and Their Metabolites After Application of MC2-01 Cream Compared With Active Comparator in Subjects With Extensive Psoriasis Vulgaris
Phase: PHASE2
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics

MC2 Therapeutics 
 
Protocol MC2-01-C3 
Date: 20 Dec 2017 
 
Clinical Trial Protocol 
 
Trial Title: 
A Randomised, Multicentre, Open-label, Parallel-group 
Maximal Use Trial, Evaluating the Pharmacokinetic Profile 
of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream compared with Active 
Comparator in Subjects with Extensive Psoriasis Vulgaris
  
Investigational product: 
MC2-01 (calcipotriene/betamethasone dipropionate, w/w 
0.005%/0.064%) Cream 
 
Active Comparator: 
Taclonex® (calcipotriene and betamethasone dipropionate, 
w/w 005%/0.064%) Ointment 
 
Protocol No: 
MC2-01-C3 
 
IND: 
127152 
 
Development phase: 
2 
 
Documents status: 
Final 
 
Document version: 
Version 3.0 
 
Document date:  
20 December 2017 
 
  
 
 
 
 
Sponsor: 
 
 
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
 
 
 
 
c/o Agern Alle 24-26 
 
 
 
 
2970 Hørsholm 
 
 
 
 
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-C3 
20 December 2017 
 
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CLINICAL TRIAL PROTOCOL APPROVAL 
Product: MC2-01 (calcipotriene/betamethasone dipropionate) cream 
Protocol number: MC2-01-C3 
Protocol title: A Randomised, Multicentre, Open-label, Parallel-group Maximal Use Trial, 
Evaluating the Pharmacokinetic Profile of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream compared with Active Comparator in Subjects with Extensive 
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 Clinical   
 
 
George Han, MD, PhD, International Coordinating Investigator, Department of Dermatology, 
Mount Sinai Beth Israel                             
 
 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
- 3 - 
SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
Product: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%)   
                cream 
Protocol number: MC2-01-C3 
Version: 3 
Protocol title: A Randomised, Multicentre, Open-label, Parallel-group Maximal Use Trial, 
Evaluating the Pharmacokinetic Profile of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream compared with Active Comparator in Subjects with Extensive 
Psoriasis Vulgaris. 
The signature of the trial investigator below constitutes his/her approval of this protocol and 
provides the necessary assurances that this trial will be conducted according to all stipulations, 
clinical and administrative, as detailed in the protocol. The trial will not be initiated without 
the approval of an appropriate Institutional Review Board or Ethics Review Committee. 
 
 
 
Principal Investigator’s printed name 
 
 
 
 
Principal Investigator’s signature 
 
Date 
 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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TABLE OF CONTENTS 
TABLE OF CONTENTS ..............................................................................................................4 
LIST OF TABLES .........................................................................................................................7 
LIST OF FIGURES .......................................................................................................................7 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ...............................................8 
1.0 
SYNOPSIS ..........................................................................................................................10 
2.0 
INTRODUCTION ..............................................................................................................14 
2.1 
Background ..............................................................................................................14 
2.2 
Rationale of the Trial ................................................................................................15 
2.3 
Benefit-risk Assessment ...........................................................................................17 
3.0 
TRIAL OBJECTIVES AND PURPOSE ..........................................................................17 
4.0 
TRIAL DESIGN .................................................................................................................18 
4.1 
Overall Trial Design .................................................................................................18 
4.2 
Trial Endpoints .........................................................................................................19 
5.0 
SELECTION OF TRIAL POPULATION .......................................................................21 
5.1 
Subject Population ....................................................................................................21 
5.2 
Inclusion Criteria ......................................................................................................21 
5.3 
Exclusion Criteria .....................................................................................................22 
5.4 
Withdrawals and Discontinuation of Treatment ......................................................24 
5.5 
Replacement Policy ..................................................................................................25 
6.0 
TRIAL TREATMENTS ....................................................................................................25 
6.1 
Investigational Product .............................................................................................25 
6.2 
Active Comparator ...................................................................................................25 
6.3 
Dosing Regimen .......................................................................................................25 
6.4 
Dose Modification ....................................................................................................26 
6.5 
Packaging, Labeling and Storage .............................................................................26 
6.6 
Assignment to Treatment .........................................................................................26 
6.6.1 
Randomisation ..............................................................................................26 
6.6.2 
Blinding ........................................................................................................26 
6.7 
Prior, Concomitant, and Prohibited Therapy ...........................................................27 
6.7.1 
Washout of prohibited medications prior to enrolment ...............................27 
6.7.2 
Prohibited medications during the trial ........................................................27 
6.7.3 
Allowed treatment on the face, skin folds, and genital skin only ................27 
6.8 
Treatment Compliance .............................................................................................27 

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Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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7.0 
VISIT SCHEDULE AND ASSESSMENTS .....................................................................29 
7.1 
Visit Schedule for Screening and until Randomisation ...........................................29 
7.2 
Visit Schedule and Assessment for Subjects Assigned the MC2-01 Cream ............31 
7.3 
Visit Schedule and Assessments for Subjects Assigned the Comparator ................33 
7.4 
Demographics and Medical History .........................................................................35 
7.5 
Prior and Concomitant Medication ..........................................................................35 
7.6 
Physical Examination ...............................................................................................35 
7.7 
Vital Signs ................................................................................................................36 
7.8 
Urine Pregnancy Test ...............................................................................................36 
7.9 
Laboratory Assessments ...........................................................................................36 
7.9.1 
Hematology, biochemistry and urinalysis ....................................................36 
7.9.2 
HPA axis suppression/ ACTH challenge test ...............................................36 
7.9.3 
Food diary: calcium-rich nutrients ...............................................................37 
7.9.4 
24-hour urinalysis .........................................................................................37 
7.9.5 
Pharmacokinetics .........................................................................................38 
7.10 
Electrocardiogram ....................................................................................................38 
7.11 
The Psoriasis Treatment Convenience Scale ...........................................................39 
7.12 
Investigator Assessments .........................................................................................39 
7.12.1 
Physician’s global assessment of psoriasis severity .....................................39 
7.12.2 
Body surface area involvement of psoriasis vulgaris ...................................40 
7.12.3 
Local skin reactions ......................................................................................41 
7.13 
Adverse Events .........................................................................................................42 
7.13.1 
Adverse events assessments .........................................................................42 
7.13.2 
Timing ..........................................................................................................43 
7.13.3 
Severity of adverse events ............................................................................43 
7.13.4 
Relationship of an adverse event to trial treatment ......................................44 
7.13.5 
Unexpected adverse events ..........................................................................44 
7.13.6 
Trial medication overdose ............................................................................45 
7.13.7 
Pregnancy .....................................................................................................45 
7.13.8 
Serious adverse event ...................................................................................45 
7.14 
Unscheduled Visit ....................................................................................................46 
7.15 
Follow-up Visit ........................................................................................................46 
7.16 
Early Termination ....................................................................................................46 
8.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
STATISTICAL AND ANALYTICAL PLANS ...............................................................47 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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8.1 
General Considerations for Data Analysis ...............................................................47 
8.2 
Sample Size and Power Considerations ...................................................................47 
8.3 
Analysis Populations ................................................................................................47 
8.4 
Background and Demographic Characteristics ........................................................48 
8.5 
Trial Medication/Exposure .......................................................................................48 
8.6 
Prior and Concomitant Therapy ...............................................................................48 
8.7 
Analysis of Pharmacokinetics ..................................................................................48 
8.8 
Analysis of Safety ....................................................................................................49 
8.8.1 
HPA-axis suppression ..................................................................................49 
8.8.2 
Calcium metabolism endpoints ....................................................................49 
8.8.3 
Adverse events .............................................................................................49 
8.8.4 
Other safety variables ...................................................................................50 
8.9 
Analysis of Other Endpoints ....................................................................................50 
8.9.1 
Physician global assessment .........................................................................50 
8.9.2 
Psoriasis treatment convenience scale ..........................................................50 
8.10 
Quality of Life Analysis (Not Applicable) ...............................................................50 
9.0 
CHANGES IN THE PLANNED TRIAL .........................................................................50 
9.1 
Protocol Amendments ..............................................................................................50 
9.2 
Termination or Suspension of the Trial ....................................................................51 
10.0 DATA HANDLING AND RECORD KEEPING ............................................................51 
10.1 
Recording of Data ....................................................................................................51 
10.1.1 
Source documents ........................................................................................51 
10.1.2 
Case report forms .........................................................................................51 
10.2 
Retention of Documents ...........................................................................................52 
11.0 QUALITY CONTROL AND QUALITY ASSURANCE ...............................................52 
11.1 
Direct Access to Source Documents ........................................................................52 
11.2 
Monitoring Procedures .............................................................................................52 
11.3 
Audit and Inspection ................................................................................................52 
12.0 ETHICS ...............................................................................................................................53 
12.1 
Ethical Conduct of the Trial .....................................................................................53 
12.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) ...........53 
12.3 
Subject Information and Consent .............................................................................53 
12.4 
Disclosure and Confidentiality .................................................................................53 
12.4.1 
Confidentiality of trial documentation .........................................................53 
12.4.2 
Privacy of individual health information .....................................................53 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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13.0 EMERGENCY PROCEDURES .......................................................................................54 
13.1 
Emergency Unblinding (Not Applicable) ................................................................54 
13.2 
Reporting of Serious Adverse Events and Pregnancies ...........................................54 
13.2.1 
Contact person(s) and number(s) .................................................................54 
13.2.2 
Reporting procedures ...................................................................................54 
14.0 INSURANCE ......................................................................................................................54 
15.0 PUBLICATION POLICY .................................................................................................54 
16.0 REFERENCES ...................................................................................................................55 
17.0 APPENDICES ....................................................................................................................57 
17.1 
Appendix 1 Contact List of MC2 and Protocol Authors ..........................................57 
17.2 
Appendix 2 Vendors .................................................................................................58 
 
 
LIST OF TABLES 
 
Table 7-1 Visit Schedule for Screening until Randomisation .....................................................29 
Table 7-2 Visit Schedule for Subjects Assigned to the MC2-01 Cream .....................................31 
Table 7-3 Visit Schedule for Subjects Assigned to the Comparator ...........................................33 
Table 7-4 Fitzpatrick Skin Type Classification ..........................................................................35 
Table 7-5 Physician’s Global Assessment (PGA) ......................................................................40 
Table 7-6 Local Skin Reaction Scores ........................................................................................42 
 
LIST OF FIGURES 
Figure 4-1  Trial Design for Subjects Assigned to the MC2-01 Cream ........................................19 
Figure 4-2  Trial Design for Subjects Assigned to the Active Comparator ..................................19 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Abbreviation 
Definition 
ACE 
Angiotensin converting enzyme 
ACTH 
Adrenocorticotropic hormone  
AE 
Adverse event 
ALP 
Alkaline phosphatase 
AUC0-7 
Area under the time-concentration curve from time zero to 7 hours 
AUC0-t 
Area under the time-concentration curve from time zero to the last 
measurable concentration 
AUC0-∞ 
Area under the time-concentration curve from time zero to infinity 
BDP 
Betamethasone dipropionate 
BSA 
Body surface area 
CAL 
Calcipotriene (United States term) / Calcipotriol (European Union term) 
Cmax 
Maximum plasma drug concentration 
CRO 
Contract Research Organisation 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EU 
European Union 
FDA 
Food and Drug Administration 
FU1, FU2 
Follow up visit 1, Follow up visit 2 
HIV 
Human immunodeficiency virus 
HPA 
Hypothalamic-pituitary-adrenal 
ICF 
Informed consent form 
ICH-GCP 
International Conference on Harmonisation-Good Clinical Practice 
IEC 
Independent Ethics Committee 
IP 
Investigational product 
IRB 
Institutional Review Board 
IWR 
Interactive web response  
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
OTC 
Over the counter 
PGA 
Physician’s Global Assessment 
PK 
Pharmacokinetics 
PTH 
Parathyroid hormone 
PUVA 
Psoralen + ultraviolet A 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAR 
Suspected adverse reaction 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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Abbreviation 
Definition 
SD 
Standard deviation 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
SV1, SV2 
Screening Visit 1, Screening Visit 2 
T1/2 
Elimination half-life 
TH17 
T helper 17 (cell) 
Tmax 
Time to maximum plasma drug concentration 
UBC  
United BioSource Corporation 
UPT 
Urine pregnancy test 
US  
United States 
UVA / UVB 
Ultraviolet A / ultraviolet B 
WBC 
White blood cell 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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1.0 
SYNOPSIS 
Trial Title: 
A Randomised, Multicentre, Open-label, Parallel-group Maximal Use Trial, 
Evaluating the Pharmacokinetic Profile of the Active Ingredients and their 
Metabolites after application of MC2-01 Cream compared with Active 
Comparator in Subjects with Extensive Psoriasis Vulgaris.  
Protocol Number: 
MC2-01-C3 
Sponsor:  
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
 
Development Phase: 
2 
Trial Objectives: 
The primary objective is to evaluate the pharmacokinetic profile of the active 
ingredients and their main metabolites after application of MC2-01 cream, and 
compare with the active comparator following once daily topical application 
under maximum-use conditions in subjects with extensive psoriasis vulgaris. 
The secondary objective is to evaluate the effect of MC2-01 cream on the 
hypothalamic-pituitary-adrenal (HPA) axis and calcium metabolism following 
once daily topical application under maximum-use conditions in subjects with 
extensive psoriasis vulgaris. 
Trial Design: 
This is a Phase 2, randomised, open-label, parallel-group, multicentre trial in 
which the investigational product, MC2-01 cream, and 
calcipotriene/betamethasone ointment (comparator) is investigated in subjects 
with clinically diagnosed extensive psoriasis vulgaris.  
After having provided informed consent, the subjects will undergo screening 
procedure. Subjects that fulfil the inclusion and exclusion criteria are randomly 
assigned in a 1:1 ratio to receive the MC2-01 cream or the comparator. 
Subjects assigned to the MC2-01 cream will be treated once-daily for 8 weeks 
and the subjects assigned to the comparator will be treated once-daily for 4 
weeks.   
At Week 4, the pharmacokinetic (PK) profile of calcipotriene (CAL), 
betamethasone dipropionate (BDP) and their main metabolites MC1080 and 
betamethasone 17-propionate, respectively, will be assessed for both treatment 
groups. At Week 8, the PK profile of calcipotriene, betamethasone and their 
main metabolites will be assessed for the MC2-01 cream treatment group only. 
The effect of use of MC2-01 cream on the hypothalamus-pituitary-adrenal 
(HPA) axis and calcium metabolism will be evaluated at week 4 and week 8. 
The maximum trial duration for each subject will be approximately 12 or 16 
weeks and includes a screening period of up to 4 weeks (if washout of 
medication is required), a treatment period of 4 or 8 weeks, and a follow-up 
period of up to 4 weeks (if required for follow-up of adverse events, calcium 
concentrations, and/or HPA axis suppression).  

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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Sample Size: 
It is planned to enrol approximately 60 subjects with the aim to have 25 subjects 
included in the PK population after 4 weeks of treatment in each treatment arm.  
The choice of sample size in this trial is not based on statistical considerations, 
but rather on regulatory considerations with respect to common practice in 
maximum use studies evaluating pharmacokinetic profiles and evidence of HPA 
safety 
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, with a Physician Global Assessment (PGA) of disease severity of at 
least moderate on the trunk, limbs and/or scalp and a treatment area between 
20% and 30% of the BSA, excluding psoriatic lesions on the face, genitals, and 
intertriginous areas. 
Investigational Product(s): 
MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%).  
Reference Product(s): 
CAL/BDP ointment (w/w 0.005%/0.064%). Approved in the United States 
(US) as Taclonex® Ointment and in rest of the world as Daivobet® 
Ointment/Dovobet® Ointment. 
Pharmacokinetics Evaluation 
Criteria: 
Blood samples for PK assessments will be collected at 
• 
SV2 (baseline sample)   
• 
Week 2 
• 
Week 4 and for subjects assigned to the MC2-01 cream at Week 8; 
before application of trial medication and then at 0.5, 1, 2, 3, 5, and 7 
hours after the application.  
The samples will be assayed for concentrations of the active ingredients (BDP 
and CAL) and for their main metabolites; betamethasone 17-propionate and 
MC1080, respectively. 
HPA axis and calcium 
metabolism Evaluation 
Criteria: 
For subjects assigned to the MC2-01 cream, the endpoint for the HPA axis 
evaluation will be a serum cortisol level of 18 µg/dL or less at 30 minutes after 
ACTH challenge at Week 4 and Week 8: 
The primary response criteria for calcium metabolism will be changes from 
Baseline to Week 4 and Week 8 in: 
• 
Albumin-corrected serum calcium; 
• 
24-hour urinary calcium excretion; 
• 
Ratio of urinary calcium to creatinine. 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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Other Safety Evaluation 
Criteria 
Adverse event incidence and severity, laboratory test results (haematology, 
clinical chemistry, urinalysis), vital signs, local skin reactions, physical 
examination. For subjects assigned to the MC2-01 cream electrocardiogram 
(ECG). 
Statistical Methods: 
It is planned to combine the data from all centres that participate in this protocol, 
in order to have an adequate number of subjects for analysis. No imputation will 
be made for missing data. 
Primary endpoint: 
Systemic PK profile of the active ingredients of the MC2-01 cream and their 
main metabolites following once daily topical application for 4 weeks. 
All available concentration results will be summarised using appropriate 
descriptive statistics for active ingredients (BDP and CAL) and for their major 
metabolites. Median and individual concentration versus time curves will be 
plotted (linear and semi-log plots). 
Plasma PK parameters (AUC0-t, AUC0-∞, AUC0-7, Cmax, and Tmax, and T½) will 
be calculated. For a given analyte, the PK parameters AUC0-t, AUC0-∞, Tmax, 
and T½ will be calculated if data allow. The PK parameters AUC0-7 and Cmax 
will be calculated using standard formulas inserting the lower limit of 
quantification (LLoQ) in case of concentrations below the LLoQ, in which 
case the result is an upper limit for the PK parameter. The PK parameters will 
be summarised using appropriate descriptive statistics. The PK parameters 
AUC0-7 and Cmax will be compared for the two treatment groups using analysis 
of variance for censored data. 
Only for subjects assigned to the MC2-01 cream:  
Systemic PK profile of the active ingredients of the MC2-01 cream and their 
main metabolites following once daily topical application for 8 weeks. 
The PK parameters AUC0-t, AUC0-∞, AUC0-7, Cmax, Tmax, and T½ will be 
calculated and presented as described for Week 4. 
Secondary endpoints for subjects assigned to the MC2-01 cream: 
HPA axis suppression 
The proportion of subjects with HPA-axis suppression at Week 4 and at Week 8 
will be summarised using frequency counts.  
Calcium metabolism endpoints: 
Summary statistics will be provided for the following:  
Observed values of and changes from Baseline (SV2) to Week 4 and Week 8 in: 
• 
Albumin-corrected serum calcium 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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• 
24 hours’ urinary calcium excretion 
• 
Ratio of urinary calcium to creatinine. 
Other safety endpoints: Adverse events will be presented in data listings and 
summarised by frequency and severity for each treatment group. Laboratory, 
ECG, and vital sign data will be presented in data listings. Abnormal ECG and 
laboratory findings will be presented 
Trial Sites: 
10-15 sites in US 
Planned Dates of Trial: 
4th quarter, 2017 - 3nd quarter, 2018 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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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 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 (BDP) is superior to each of the single agent11-12.There is strong scientific rationale 
for the combination of vitamin D and glucocorticosteroids both with respect to efficacy and 
safety13-15, and combination treatment with a Vitamin D analog and a topical corticosteroid is 
recommended in both American and European guidelines16-19 
CAL and BDP are incompatible in an aqueous environment, since CAL requires basic conditions 
to maintain stability while betamethasone requires acidic conditions. Currently marketed products 
are therefore restricted to non-aqueous, oil-based formulations. 
The 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. 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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Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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2.2 
Rationale of the Trial 
To increase the likelihood that adequate quantifiable systemic concentrations of CAL and BDP 
and their main metabolites under maximal use conditions to determine the pharmacokinetic 
parameters in sufficient numbers of patients, Taclonex® Ointment has been selected as the 
comparator. MC2-01 cream will be compared to Taclonex® Ointment following once daily 
topical application under maximal use conditions in subjects with extensive psoriasis on the 
scalp, trunk, and limbs. Dosages will be up to 100 g per week for 8 weeks for MC2-01 cream and 
for 4 weeks for Taclonex® Ointment.  
 
At Week 4, blood samples will be taken at selected intervals after topical dosing of each trial 
medication. Upper limits will be calculated for the PK parameters, area under the concentration-
time curve (AUC) from time zero to the planned last PK blood sampling time point of 7 hours 
(AUC0-7) and maximum plasma drug concentration (Cmax). To the extent the data allow to 
calculate the PK parameters, the following parameters will be calculated: AUC from time zero to 
the last quantifiable concentration (AUC0-t), AUC from time zero to infinity (AUC0-∞), time to 
maximum plasma drug concentration (Tmax), and elimination half-life (T½).  
 
Taclonex® Ointment is only approved for daily application for up to 4 weeks, whereas it is the 
intention that MC2-01 cream will be used daily for up to 8 weeks. The pharmacokinetic 
comparison between the two trial medications will be done at Week 4. Additional 
pharmacokinetic data at Week 8 will be obtained only from subjects receiving the MC2-01 
cream.  
 
Since MC2-01 cream is a combination of CAL and BDP, disturbance of calcium metabolism and 
adrenal function respectively could theoretically be the result if these two components are 
absorbed through the skin.  
 
As the current trial is a MUsT trial only subjects with upper level of disease involvement will be 
included. Inclusion criteria will be subjects with extensive psoriasis covering between 20-30% of 
the BSA on trunk, limbs and/or scalp. The intent of the inclusion criteria is both to take into 
account the potential risk that patients may decide to apply MC2-01 cream on the scalp and also 
to take into account precedent from previous approved CAL/BPD products. 
 
According to input from experienced investigators, subjects with extensive vulgaris psoriasis 
may have psoriasis elements of guttatae character. Considering that the histological 
characteristics of guttate psoriasis and the clinical response to Vitamin D and glucocorticoids are 
similar to what is observed in subject with psoriasis vulgaris, presence of psoriasis elements of 
guttate character will not be an exclusion criterium in this study. 
  

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Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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To evaluate the safety of the MC2-01 cream, all adverse events (AEs), reported by the subject or 
observed by the investigator, are recorded. In addition, any effects resulting from systemic 
absorption of the active components, BDP and CAL, are evaluated by assessing adrenal function 
and calcium metabolism, respectively. Adrenal function can therefore be measured by injection 
of a synthetic subunit of ACTH into the subject, and then measuring the production of cortisol by 
the adrenal glands in response to this. In the present study, enrolled subjects in the MC2-01 arm 
of the study will be subjected to an ACTH-challenge test before and after 4 and 8 weeks’ 
treatment.  
Overdosage with topical CAL can cause hypercalcemia20 due to the systemic absorption of CAL, 
which then affects calcium metabolism as it is a vitamin D analogue. However, extensive 
experience with topical use of CAL in psoriasis has demonstrated no significant impact on 
calcium metabolism, when used in the recommended amounts (maximum weekly dose in adults 
of 100 g of a 50 mcg/g concentration). Doses up to 300 g have been used with serum calcium 
remaining within the reference range21. Calcium metabolism will be evaluated in the present 
study by measurement of albumin corrected serum calcium, phosphate, alkaline phosphatase and 
plasma PTH before, during and after treatment. A 24-hour urine sample will be collected and the 
urinary calcium phosphate, sodium and creatinine will be measured and the urinary 
calcium:creatinine and phosphate:creatinine ratios will be calculated. It is well-established that 
there is a relationship between dietary calcium intake and the urinary calcium excretion in 
adults22. The urinary excretion of calcium has been reported to increase by 6-19 mg with each 
additional 100 mg of calcium intake22;23. Subjects will not be asked to change their diet during 
the study, but in order to limit diet-related variability in urinary calcium excretion, their normal 
consumption of calcium-rich foods will be reviewed and should be kept constant during 3 days 
prior to and during each 24-hour urinary collection. Considering that dairy products account for 
the majority of the of calcium absorption in most people, this protocol focusses on the intake of 
dairy products. The subjects will keep a diary of the daily intake of dairy products, calcium-
fortified products (e.g. bread, cereals, orange juice or soy milk) and other specified calcium-rich 
products. The number of daily servings of calcium defined as 240 mL (one US cup) in dairy 
products such as milk or yoghurt or of a calcium-fortified product with corresponding calcium 
content (300 mg calcium per 240mL/one US cup) or 42g (1.5 ounces) of cheese. As an extreme 
calcium intake has been shown to significantly increase urinary excretion of calcium, subjects 
will be instructed not to consume more than five daily calcium servings (i.e. 1500 mg calcium). 
The combination of high calcium intake with vitamin D supplementation significantly increases 
urinary calcium. Hence the use of calcium or vitamin D supplements were excluded in this study 
with the exception of stable doses of oral vitamin D (up to 400 IU/day) at baseline with no dose 
adjustment during the study period. Systemic safety of MC2-01 cream on calcium metabolism 
and HPA axis will be assessed at Week 4 and Week 8. Experience with the current commercially 
available fixed-dose combinations of CAL and BDP has shown that effects on HPA axis 
suppression or calcium homeostasis are infrequent events. For this reason, post-Baseline HPA 

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axis suppression and calcium homeostasis testing will be performed only in subjects receiving 
the MC2-01 cream, without any comparison to the reference compound.  
 
Data from this trial, together with the measurements of albumin-corrected serum calcium and the 
calcium:creatinine ratio in urine samples in the phase 3 trial with MC2-01 cream are expected to 
provide adequate information with respect to the systemic safety of the MC2-01 cream. 
 
2.3 
Benefit-risk Assessment 
The subject population will be composed of subjects with psoriasis that is at least moderate in 
severity according to PGA and involves 20-30% of body surface area (BSA), excluding face, 
genitals and intrigenous areas, in order to evaluate the trial medication under maximum use 
conditions.  
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 acceptability to patients than the currently available formulations.  
The side effects reported with CAL/BDP topical formulations are mild and reversible upon 
stopping therapy. It is therefore not considered necessary to have analysis of calcium homeostasis 
prior to initiation of treatment. Subjects in this trial will be monitored for both systemic and local 
safety during the trial.  
Clinical signs or symptoms of systemic safety (e.g., hypercalcemia, HPA axis suppression, or 
cardiac safety) will be part of the periodic assessment of subjects throughout this trial. In addition, 
for subjects assigned to the MC2-01 Cream, an ACTH challenge test supplemented with 
measurement of albumin corrected calcium, and total calcium excretion will be performed at Week 
4 and Week 8. 
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 outcome24. 
3.0 
TRIAL OBJECTIVES AND PURPOSE 
The primary objective is to evaluate the pharmacokinetic profile of the active ingredients after 
application of MC2-01 cream and their main metabolites, and compare with the active 

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comparator following once daily topical application under maximum-use conditions in subjects 
with extensive psoriasis vulgaris. 
The secondary objective is to evaluate the effect of MC2-01 cream on the hypothalamic-pituitary-
adrenal (HPA) axis and calcium metabolism following once daily topical application under 
maximum-use conditions in subjects with extensive psoriasis vulgaris. 
4.0 
TRIAL DESIGN 
4.1 
Overall Trial Design 
This is a Phase 2, randomised, open-label, parallel-group, multicentre trial in which the 
investigational product, MC2-01 cream, and CAL/BDP ointment (comparator) are investigated 
in subjects with clinically diagnosed extensive psoriasis vulgaris.  
After having provided written informed consent, the subject will undergo screening procedures. 
Subjects who meet the trial entry criteria will be randomly assigned in a 1:1 ratio to receive either 
MC2-01 cream or the comparator, CAL/BDP ointment. Subjects assigned to MC2-01 cream will 
apply 1 dose of trial medication topically once daily for 8 weeks and the subjects assigned to the 
comparator will apply 1 dose of trial medication topically once daily for 4 weeks. 
Please refer to Figure 4-1 for an overview of the trial design for subjects assigned to the MC2-01 
cream and refer to Figure 4-2 for an overview of the trial design for subjects assigned to the active 
comparator. 
Trial subjects will be enrolled at approximately 10-15 sites in US.  
At Week 4, the pharmacokinetic (PK) profile of calcipotriene (CAL), betamethasone dipropionate 
(BDP) and their main metabolites MC1080 and betamethasone 17-propionate, respectively, will 
be assessed for both treatment groups. At Week 8, the PK profile of CAL, BDP and their main 
metabolites will be assessed for the MC2-01 cream treatment group only. At Week 4 and Week 8, 
the effect of once-daily use of MC2-01 cream on the HPA axis and calcium metabolism will be 
evaluated for MC2-01 cream treatment group. Other safety assessments (local skin reactions, AEs, 
laboratory tests, electrocardiogram (ECG)), vital signs and physical examinations) and efficacy 
assessments are also performed.  
The maximum trial duration for each subject will be approximately 12 or 16 weeks and includes a 
screening period of up to 4 weeks (if washout of medication is required), a treatment period of 4 or 
8 weeks, and a follow-up period of up to 4 weeks (if required for follow-up of adverse events, 
calcium concentrations, and/or HPA axis suppression).  
During the trial, the effect of once-daily use of MC2-01 cream on the HPA axis and calcium 
metabolism will be evaluated for subjects assigned to the MC2-01 cream. Systemic exposure will 
be assessed for both treatment groups at Week 4, and additionally at Week 8 for the subjects 

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assigned to the MC2-01 cream. Other safety assessments (local skin reaction, AEs, laboratory tests, 
electrocardiogram (ECG), vital signs and physical examinations) and efficacy assessments are also 
performed.  
Figure 4-1  
Trial Design for Subjects Assigned to the MC2-01 Cream 
 
        
 
      Screening Period 
      8 Weeks Treatment period 
               Follow-up Period* 
 
 
 
 
 
Baseline 
End of 
 
Days -30 to - 4 
Visit SV1 
 
  Day 0              Weeks 2, 4, 6 
 Visit 1               Visits 2, 3, 4 
Treatment 
Week 8 
Visit 5 
 
 
 
 
*Follow-up visits will be required only for subjects who have unresolved AEs or whose calcium levels have not returned to pre-
treatment levels at the End of Treatment visit. 
 
 
Figure 4-2  
Trial Design for Subjects Assigned to the Active Comparator 
 
                       Screening Period 
         4 Weeks Treatment period           Follow-up Period* 
 
 
 
 
 
 
 
Days -30 to - 4 
Visit SV1 
 
          Baseline 
          Day 0     Week 2 
          Visit 1     Visit 2 
 
End of 
Treatment 
Week 4 
 
 
 
 
 
*Follow-up visits will be required only for subjects who have unresolved AEs at the End of Treatment visit. 
4.2 
Trial Endpoints 
Primary Endpoints 
For all subjects:  
Pharmacokinetic (PK) parameters (AUC0-t, AUC0-∞, AUC0-7, Cmax, Tmax, and T½) of active 
ingredients and their main metabolites at Week 4. For a given analyte, the PK parameters 
AUC0-t, AUC0-∞, Tmax, and T½ will be calculated if data allow. The PK parameters AUC0-7 and 
Cmax will be calculated for all subjects; AUC0-7 will be an upper limit in case at least one time 
point shows a non-quantifiable level of the analyte, and Cmax will be an upper limit in case all 
MC2-01 cream 
Active  Comparator 

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time points show non-quantifiable levels of the analyte. Tmax will be calculated in case at least 
one time point shows quantifiable levels of the analyte. 
For subjects assigned to the MC2-01 cream:  
PK parameters (AUC0-t, AUC0-∞, AUC0-7, Cmax, Tmax, and T½) of active ingredients and their main 
metabolites at Week 8. For a given analyte, PK parameters will be calculated under similar 
conditions as described for Week 4. 
Secondary Endpoints  
HPA axis evaluation for subjects assigned to the MC2-01 cream:  
The number of subjects with a serum cortisol level of 18 µg/dL or less at 30 minutes after ACTH 
challenge at Week 4 or Week 8.   
Calcium metabolism evaluation for subjects assigned to the MC2-01 cream:  
Changes from Baseline to Week 4 or Week 8 in: 
• Albumin-corrected serum calcium; 
• 24-hour urinary calcium excretion; 
• Ratio of urinary calcium to creatinine.  
Safety Endpoints  
Safety endpoints include the following: 
• Local skin reaction; 
• Adverse events (AEs) and serious adverse events (SAEs); 
• Changes in safety laboratory test results; 
• Changes in ECGs (Only for subjects assigned to the MC2-01 cream); 
• Changes in vital signs and physical examinations. 
Other Endpoints 
• For all subjects:  
The proportion of subjects with treatment success, defined as a minimum 2-point 
decrease from Baseline in the physician’s global assessment (PGA) on the scalp, trunk, 
and limbs at Week 4. 

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• For subjects assigned to the MC2-01 cream:  
The proportion of subjects with treatment success, defined as a minimum 2-point 
decrease from Baseline in the PGA on the trunk, limbs, and scalp at Week 8. 
• For all subjects:  
Subject assessment of treatment convenience at Week 4 using a Psoriasis Treatment 
Convenience Scale.  
5.0 
SELECTION OF TRIAL POPULATION 
5.1 
Subject Population 
A sufficient number of subjects will be enrolled in order to provide 25 subjects in each treatment 
arm, who are included in the PK analysis at Week 4. 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 (ICF) 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. 
At Visit 1/Day 0, have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 
6 months duration involving trunk, limbs and/or scalp that is amenable to topical treatment 
with a maximum of 100 g of trial medication per week. 
4. 
Have a PGA of severity of at least moderate on the trunk, limbs and/or scalp, excluding 
psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0. 
5. 
Have a treatment area between 20% and 30% of the BSA on the trunk, limbs and/or scalp, 
excluding psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0. 
6. 
Female subjects must be of either: 
• Non-childbearing potential, i.e., post-menopausal for a least 1 year or have a 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. 

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7. 
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 fulfil any of the following criteria will be ineligible to participate in the trial: 
1. 
Have a current diagnosis of unstable forms of psoriasis, including 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. 
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; 
6. 
Current or past history of disorders of calcium metabolism associated with 
hypercalcemia, vitamin D toxicity, severe renal insufficiency, or severe hepatic disorders; 
7. 
Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within 
4 weeks prior to Visit 1/Day 0 during the trial period.  
Note: Stable doses of oral vitamin D supplementation ≤400 IU/day are permitted 
provided there are no dose adjustments during the trial period; 
8. 
Planned initiation of, or changes to concomitant medication that could affect calcium 
metabolism (e.g., antacids, thiazide and/or loop diuretics, antiepileptics) during the trial; 
9. 
Planned initiation of, or changes to, concomitant estrogen therapy during the trial; 
10. Strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., clarithromycin, 
telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, 
lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) within 4 weeks prior to Vist 1/Day 
0 and during the trial period; 
11. Use of topical treatments (eg, corticosteroids, vitamin D analogs, retinoids, PDE4 
inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar), except for emollients 

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and non-medicated shampoos, with a possible effect on psoriasis within 2 weeks prior to 
Visit 1/Day 0 and during the trial period;  
12. Systemic treatment with biological therapies (whether marketed or not marketed), with a 
possible effect on psoriasis vulgaris within the following time period prior to Visit 1/Day 
0 and during the trial period; 
• etanercept – within 4 weeks 
• adalimumab, alefacept, infliximab – within 8 weeks 
• ustekinumab – within 16 weeks 
• other products – within 4 weeks/5 half-lives (whichever is longer) 
13. Initiation of, or expected changes to, concomitant medication that may affect psoriasis (e.g., 
beta-blockers, chloroquines, lithium, and angiotensin converting enzyme [ACE] inhibitors) 
and during the trial period; 
14. Any of the following conditions, whether known or suspected: 
• depression and endocrine disorders (e.g. Cushing’s disease, Addison’s disease, 
diabetes mellitus) known to affect cortisol levels or HPA axis integrity  
• Non-nocturnal sleep patterns (e.g. night shift workers); 
15. Use of systemic medication that suppresses the immune system (e.g, 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 Visit 1/Day 0 and during the trial 
period; 
16. Have clinical signs of skin infection with bacteria, viruses, or fungi; 
17. Known human immunodeficiency virus (HIV) infection; 
18. Known or suspected of hypersensitivity to any component of the test product or reference 
product; 
19. Have any chronic or acute medical condition that, in the option 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; 
20. 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 or will 
interfere with the interpretation of the trial results; 
21. Females who are pregnant, breast feeding, or planning a pregnancy; 

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22. Participation in another clinical trial or received an investigational product or non-
marketed drug substances within 30 days; 
23. Previously enrolled in this trial; 
24. In the opinion of the (sub)investigator, the subject is unlikely to comply with the clinical 
trial protocol; 
 
5.4 
Withdrawals and Discontinuation of Treatment 
In accordance with legal requirements and International Conference on Harmonization (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 subject should be 
advised on follow-up safety evaluations.  
If HPA axis is suppressed at Visit 1/Day 0 or Week 4, the subject should be contacted and the 
application with the investigational product (IP) should be discontinued (see Section 7.9.2 and 
Section 7.16).  
If albumin corrected serum calcium is above upper limit at Visit1/Day 0, the application with the 
investigational product (IP) should be discontinued (see Section 7.9.2).   
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, the 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. Protocol-specified withdrawal procedures are defined in Section 7.16 Early Termination. 
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. 

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5.5 
Replacement Policy 
After trial enrolment, has been completed, subjects who prematurely discontinue the trial after 
randomisation can be replaced if necessary to ensure 25 subjects in both treatment arms are 
included in the PK population at Week 4. 
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. 
6.2 
Active Comparator 
The active comparator is CAL and BDP Ointment, 0.005%/0.064%, approved in the US as 
Taclonex Ointment and in the rest of the world as Daivobet® Ointment/Dovobet® Ointment.  
Taclonex® Ointment contain the following inactive ingredients: 
• mineral oil,  
• polyoxypropylene stearyl ether  
• all-rac-alpha-tocopherol 
• butylhydroxytoluene 
• white petrolatum  
  
6.3 
Dosing Regimen 
Subjects are to apply the trial product topically once daily, preferably in the evening, to affected 
areas on the scalp and the trunk (including the neck) and/or limbs, i.e., arms (including the back 
of the hands) and/or legs (including the buttocks and the top of the feet). The face, genitals, and 
intertriginous areas should not be treated with the investigational product. The first application is 
done under the supervision and instruction of the trial staff. 
All subjects are instructed to apply the dose of trial medication in the morning on the day before 
the Week 2, Week 4 and for subjects assigned to the MC2-01 cream also at the Week 8 visit. On 
the day of the visit, the subjects should not apply any investigational product before the visit 
Subjects are to record the date and time of application in the subject dosing diary. The weekly dose 
is not to exceed 100 g for the MC2-01 cream or for the comparator. The treated area should not 
exceed 30% of the BSA.  
Detailed application instructions will be provided in the subject instructions.  

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6.4 
Dose Modification 
Until Week 4:  
Subjects classified as clear at the Week 2 visit are to continue use of the treatment unless 
investigator finds further treatments unacceptable.  
After Week 4:  
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. 
6.5 
Packaging, Labeling and Storage 
Medication labels for the investigational products will comply with the legal requirements of the 
country where the trial is performed and be printed in the local language.  
The investigational products will be supplied by MC2’s designated vendor and will be stored 
securely at the site under the control of the investigator. The temperature will be monitored and 
documented.    
The MC2-01 cream will be supplied to the clinical site(s) as tubes containing 60 g of product. The 
MC2-01 cream is to be 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. At all times, the MC2-01 cream should be protected 
from light.  
The active comparator will be supplied to the clinical sites as tubes containing 60 g of product. 
The active comparator is to be stored at 20°- 25°C (68° -77°F).  
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 1:1 ratio.  
A subject who fulfils the trial eligibility requirements will be randomly assigned to treatment. 
6.6.2 
Blinding 
This is an open-label trial with the treatment assignment known by the subjects, the investigators 
and their staff, and the clinical research team. No blinding will be performed.   

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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 enrolment 
A washout period 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 (eg, methotrexate, 
retinoids, PDE4 inhibitors, corticosteroids, and other immunosuppressants). 
• 
Use of phototherapy (PUVA and UVB). 
• 
Use of topical treatments with a possible effect on psoriasis (eg, corticosteroids, vitamin D 
analogs, retinoids, PDE4 inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar, 
etc.). 
• 
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. 
• 
Use of strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., clarithromycin, 
telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, 
lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir. 
• 
Emollients on the psoriasis affected areas. 
• 
Any medications with proven or purported activity against psoriasis (including OTC 
medications) should be discussed with the Investigator prior to use. 
6.7.3 
Allowed treatment on the face, skin folds, and genital skin only 
Subjects may receive laser treatment and use an emollient on the face, skin folds, and genital skin. 
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. 

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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 in the outer box at each visit. All returned 
tubes that had been dispensed to a subject and have broken seals will be weighed to determine the 
amount of the investigational product used per treatment phase.  
 
 

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7.0 
VISIT SCHEDULE AND ASSESSMENTS 
7.1 
Visit Schedule for Screening and until Randomisation 
 
Table 7-1 
Visit Schedule for Screening until Randomisation 
 
 
 
 
 
 
 
 
 
 
Screening 
Visit 1a 
Visit  
1 
 
Screening 
1 
Day 0 
Examination 
Day –30 to 
– 4 
Day 0  
Informed consentb 
X 
 
Inclusion/exclusion 
criteria 
[X] 
X 
Urine pregnancy test 
(UPT)c 
[X] 
X 
Demographics, 
medical history 
[X] 
X 
Prior and 
concomitant 
medication 
[X] 
X 
Physical examination 
[X] 
Xd 
PGA  
[X] 
X 
Body Surface Area 
(BSA) involvement 
[X] 
X 
Vital signs 
 
[X] 
X 
Laboratory 
assessments 
 
X 
Review food diary  
Instruct 
X 
24-h urine collection 
Instruct 
X 
Randomisation 
 
X 
Adverse event(s)e 
 
X 
Local Skin Reactions 
 
X 

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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 during screening, to assess if the subject is 
otherwise eligible. Such items must be checked for any change in eligibility status at  
Visit 1/Day 0 after the washout is completed.  
b) 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. 
c) For female subjects of childbearing potential. 
d) Including height and weight  
e) AEs are to be collected from the date of signing informed consent, i.e., during the washout 
period. 
Instruct: At the indicated visits, instruct the subjects as to appropriate trial procedures as 
specified below: 
• Food diary: instruct the subjects on how to use the food diary, especially recording their 
intake of calcium-rich nutrients 
• 24-hour urine collection: instruct the subjects on how to perform the 24-hour urine 
collection. 
 
 

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7.2 
Visit Schedule and Assessment for Subjects Assigned the MC2-01 Cream 
 
Table 7-2 
Visit Schedule for Subjects Assigned to the MC2-01 Cream 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Visit  
1 
Visit  
2 
Visit  
3 
Visit  
4 
Visit 
 5  
Follow-
up 
 Visit a 
 
Day 0 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
 
Examination 
Day 0  
Day 
14 ± 2 
Day 
28 ± 2 
Day 
42 ± 2 
Day 
56 ± 2 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
Urine pregnancy test (UPT)b 
X 
 
X 
 
X 
 
Demographics, medical 
history 
X 
 
 
 
 
 
Prior and concomitant 
medication 
X 
X 
X 
X 
X 
 
Physical examination 
Xc 
 
X 
 
X 
 
PGA  
X 
X 
X 
X 
X 
 
Body Surface Area (BSA) 
involvement 
X 
 
X 
 
X 
 
Vital signs 
X 
X 
X 
X 
X 
 
Laboratory assessments 
X 
 
X 
(X)d 
X 
X 
Review food diary  
X 
 
X 
 
X 
 
24-h urine collection 
X 
Instruct 
X 
Instruct 
X 
 
Randomisation 
X 
 
 
 
 
 
PK pre-dose blood sample 
(Single)  
X 
Instruct 
X 
 
 
 
 
PK serial blood samplese 
 
Instruct 
X 
Instruct 
X 
 
12-Lead ECG 
X 
 
X 
 
X 
 
ACTH challenge test f 
X 
 
X 
 
X 
X 
Psoriasis Treatment 
Convenience Scale 
 
 
X 
 
 
 
Dispense IP and diary for 
compliance 
X 
X 
X 
X 
 
 
Collect IP 
 
X 
X 
X 
X 
 
Compliance 
 
X 
X 
X 
X 
 
Adverse event(s)g 
X 
X 
X 
X 
X 
X 
Local Skin Reactions 
X 
X 
X 
X 
X 
 

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a) A follow-up visit is required to check: abnormal albumin-corrected serum calcium, HPA 
axis suppression, or unsolved treatment-related AEs at Week 8. 
b) For female subjects of childbearing potential. 
c) Including height and weight  
d) If serum albumin-corrected serum calcium is above the reference range at Week 4, a 
repeat test should be performed at Week 6. 
e) Blood samples for PK analysis are drawn before IP application (pre-dose sample) and 
0.5, 1, 2, 3, 5 and 7 hours after IP application. 
f)  The ACTH challenge test must be performed at 8 am (±30 minutes) before application of 
the IP. 
g) AEs are to be collected from the date of signing informed consent, i.e., during the 
washout period. 
Instruct: At the indicated visits, instruct the subjects as to appropriate trial procedures as 
specified below: 
• Food diary: instruct the subjects on how to use the food diary, especially recording their 
intake of calcium-rich nutrients 
• 24-hour urine collection: instruct the subjects on how to perform the 24-hour urine 
collection. Consumption of calcium-rich foods should be kept constant during and 3 days 
prior to each 24 hour urine collection. 
• PK blood samples: instruct the subjects that the day before the Week 2, Week 4, and 
Week 8 visits, they should apply the trial drug in the morning. On the day of the visit, the 
subjects should not apply any investigational product before the visit, but will apply the 
IP after the pre-dosing PK sample has been drawn. A reminder to the subjects may be 
needed a few days before the scheduled visit. If the subject has applied the investigational 
product in the morning prior to the visit, the visit must be rescheduled.  

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7.3 
Visit Schedule and Assessments for Subjects Assigned the Comparator 
 
Table 7-3 
Visit Schedule for Subjects Assigned to the Comparator 
 
Visit  
1 
Visit  
2 
Visit  
3 
Follow-up 
 Visita 
 
Day 0 
Week 2 
Week 4 
 
Examination 
Day 0  
Day 14 
± 2 
Day 28 
± 2 
 
Inclusion/exclusion criteria 
X 
 
 
 
Urine pregnancy test (UPT)b 
X 
 
X 
 
Demographics, medical history 
X 
 
 
 
Prior and concomitant 
medication 
X 
X 
X 
 
Physical examination 
Xc 
 
X 
 
PGA  
X 
X 
X 
 
Body Surface Area (BSA) 
involvement 
X 
 
X 
 
Vital signs 
X 
X 
X 
 
Laboratory assessments 
X 
 
X 
 
Review food diary 
X 
 
 
 
24-h urine collection 
X 
 
 
 
PK pre-dose blood sample 
(Single)  
X 
Instruct 
X 
 
 
PK serial blood samplesd 
 
Instruct 
X 
 
Randomisation 
X 
 
 
 
 Psoriasis Treatment 
Convenience Scale 
 
 
X 
 
Dispense IP and diary for 
compliance 
X 
X 
X 
 
Collect IP 
 
X 
X 
 
Compliance 
 
X 
X 
 
Adverse event(s)e 
X 
X 
X 
X 
Local Skin Reactions 
X 
X 
X 
 
 
 
 

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a) A follow-up visit is required to check unsolved treatment-related AEs at Week 4 
b) For female subjects of childbearing potential. 
c) Including height and weight. 
d) Blood samples for PK analysis are drawn before IP application (pre-dose sample) and 
0.5, 1, 2, 3, 5 and 7 hours after IP application 
e) AEs are to be collected from the date of signing informed consent, i.e., during the 
washout period. 
Instruct: At the indicated visits, instruct the subjects as to appropriate trial procedures as 
specified below: 
• Food diary: instruct the subjects on how to use the food diary, especially recording their 
intake of calcium-rich nutrients. 
• 24-hour urine collection: instruct the subjects on how to perform the 24-hour urine 
collection. Consumption of calcium-rich foods should be kept constant during and 3 days 
prior to each 24 hour urine collection. 
• PK blood samples: instruct the subjects that the day before the Week 2 and Week 4 
visits, they should apply the trial drug in the morning. On the day of the visit, the subjects 
should not apply any investigational product before the visit, but will apply the IP after 
the pre-dosing PK sample has been drawn. A reminder to the subjects may be needed a 
few days before the scheduled visit. If the subject has applied the investigational product 
on the day of the visit before the visit, the visit should be rescheduled. 
 
 

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7.4 
Demographics and Medical History 
The following demographic and medical history must be collected:  
• Date of birth 
• Sex 
• Race 
• Ethic origin 
• Complete skin disease history  
• All other current and past medical/surgical conditions within the last 12 months 
• The year diagnosed with psoriasis vulgaris 
The Fitzpatrick skin type will be assessed according to the classification scheme in Table 7-4. 
Table 7-4 
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 
  
7.5 
Prior and Concomitant Medication 
Review and record prior medication and concomitant medication. 
All medications, including 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 trial will be made. Information regarding the total daily dose, route of administration, start and 
discontinuation dates, and indication are to be recorded on the subject’s eCRF. 
7.6 
Physical Examination 
An abbreviated physical examination and dermatological examination of the skin must be 
performed, including height and weight at Visit 1/Day 0. The height and weight can be self-
reported.  

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7.7 
Vital Signs 
Blood pressure and pulse rate will be taken with the subject in the sitting position with 
approximately 5 minutes’ rest prior to measurement.  
7.8 
Urine Pregnancy Test 
Female subjects of child-bearing potential will undergo a routine urine pregnancy test at SV,  
Visit 1/Day 0, Week 4 visit and for the subjects assigned to the MC2-01 cream at the Week 8 visit. 
Instruct all female subjects to use approved form(s) of contraception.  
7.9 
Laboratory Assessments 
Clinical laboratory specimens will be analyzed by a central licensed and accredited laboratory 
facility according to the laboratory’s standard operating procedures.  
7.9.1 
Hematology, biochemistry and urinalysis 
For all subjects the following tests will be performed at Visit 1/Day 0 and the Week 4 visit and for 
subject assigned to the MC2-01 cream at the Week 8 visit: 
• Hematology: hemoglobin, hematocrit, red blood cell (RBC) count, mean corpuscular 
volume (MCV), white blood cell (WBC) count, including differential count and platelet 
count. 
• Serum biochemistry: cortisol, urea, glucose, creatinine, calcium, albumin, calcium 
(albumin corrected), sodium, potassium, chloride, calcium, phosphate, alkaline 
phosphatase (ALP), plasma parathyroid hormone (PTH).  
25-OH Vitamin D (Visit 1 only) 
Visit 1/Day 0: If serum albumin-corrected serum calcium is above the reference range at Visit 
1/Day 0, the application with the investigational product (IP) should be discontinued and an Early 
Termination visit should be performed (see Section 7.9.2). 
Week 4: If serum albumin-corrected serum calcium is above the reference range at Week 4, a 
repeat test should be performed at Week 6. If the serum albumin-corrected serum calcium is above 
the reference range at Week 8, a follow-up visit is required (see Section 7.15).  
7.9.2 
HPA axis suppression/ ACTH challenge test 
For subjects assigned to the MC2-01 cream, adrenal function will be assessed in a challenge test 
with an intravenous dose of adrenocorticotropic hormone (ACTH) (cosyntropin). Measurement of 
serum cortisol levels pre- and post- stimulation with cosyntropin 0.25 mg is the accepted standard 
method used to evaluate adrenal suppression. The ACTH challenge test will be performed at Visit 
1/Day 0, Week 4 and Week 8 visits. The test consists of blood sampling starting at 8 am (± 30 
minutes). Following the blood sample, an intravenous bolus injection of 0.25 mg cosyntropin  is 
given at time zero (t=0 minutes). Serum cortisol concentration at t=30 minutes will reflect 

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stimulation of the adrenal glands induced by cosyntropin. The ACTH challenge test must be 
performed before application of the IP. 
 Since many people do not respond to the degree expected with cosyntropin stimulation, the 
following criteria25 have been established to denote a normal response:   
1. pre-stimulation cortisol levels >5 µg/dL will be considered normal,   
2. the 30-minute post-stimulation level should show an increment of 7 µg/dL above the basal 
level, and 
3. the 30-minute post-stimulation level should exceed 18 µg/dL. 
Therefore, a basal serum cortisol level 5 µg/dL, or a 30-minute post-stimulation level  
18 µg/dL, or a post-stimulation increase (over basal) <7 µg/dL constitutes the definition of 
HPA axis suppression in the trial. 
Visit 1/Day 0: If HPA axis is suppressed at Visit 1/Day 0, the subject should be contacted because 
the application with the investigational product (IP) should be discontinued and an Early 
Termination visit should be performed (see Section 7.16). 
Week 4: If HPA axis is suppressed at Week 4, the subject should be contacted and the application 
with the MC2-01 cream should be discontinued. The subject should continue in the trial and the 
ACTH challenge test is repeated at the Week 8 visit. If HPA axis suppression is noted at Week 8, 
the subject must return for a follow-up visit (see Section 7.15).  
7.9.3 
Food diary: calcium-rich nutrients   
All subjects should record their consumption of calcium-rich nutrients (mainly milk, other dairy 
products, calcium-fortified products) three days before and during the 24-hour urine collection 
prior to Visit 1/Day 0. 
For subjects assigned to the MC2-01 cream, the same procedure will be followed before the Week 
4 and Week 8 visits. 
Based on the diary entries, the number of daily calcium servings should be calculated for each day 
and recorded in the eCRF.  
7.9.4 
24-hour urinalysis 
All subjects are to collect urine for 24 hours before Visit 1/Day 0. Subjects assigned to the MC2-
01 cream should collect urine for 24 hours before the Week 4 and Week 8 visits.  
The following urine analyses will be performed: 

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• Calcium, phosphate, creatinine, volume, total calcium excretion, total phosphate excretion, 
total creatinine excretion, urinary calcium:creatinine ratio, urinary phosphate:creatinine 
ratio. 
For follow-up on urine analysis only spot samples are performed. 
7.9.5 
Pharmacokinetics  
For all subjects, samples for PK testing will be collected though an untreated area of the skin, at 
the following time points: 
• SV2/baseline visit: single time point 
• Week 2 visit: single time point 
• Week 4 visit: before application of IP at the visit and then at 0.5, 1, 2, 3, 5, and 7 hours 
after the end of the application 
For subjects assigned to the MC2-01 cream, samples for PK testing will be collected at the 
following time points:  
• Week 8 visit: before application of trial medication at the visit and then at 0.5, 1, 2, 3, 
5, and 7 hours after the end of the application. 
Subjects are to be instructed to apply their daily dose of trial medication in the morning on the 
day before the visit and not before the visit on the day of the visit. A reminder to the subject may 
be needed a few days before the scheduled visit.  
The samples will be assayed for concentrations of the active ingredients (BDP and CAL) and for 
their major metabolites (betamethasone 17-propionate and MC180, respectively) 
7.10 
Electrocardiogram 
For all subjects assigned to the MC2-01 cream, a 12-lead ECG will be recorded at Visit 1/Day 0, 
Week 4 and Week 8 visits. Recording will take place after 5 minutes’ rest in supine position.  
Recordings will be promptly transmitted to the central ECG vendor for interpretation. Additional 
(unscheduled) ECGs can be recorded for safety reasons at any time based on the judgment of the 
investigator.  
Clinically significant findings will be reported as medical history if detected at Visit 1/Day 0. At 
subsequent visits, any new clinically significant finding will be reported as an AE. Any ECG 
abnormalities will be carefully monitored and if necessary the subject will be withdrawn from the 
trial. 

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7.11 
The Psoriasis Treatment Convenience Scale 
The Psoriasis Treatment Convenience Scale 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 (see Table 7-2, and Table 7-3).  
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 5 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 much did treating your skin disrupt your daily routine? 
5. Overall, how satisfied were you with the medical treatment? 
 
7.12 
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 Nurse Practitioner or Physician Assistant with at least 
2 years of experience in dermatology. For physicians, Nurse Practitioners and Physician Assistants 
who do not fulfill the requirement regarding dermatological experience, the person must be 
preapproved by the sponsor. The assessments are to be performed as specified in the visit schedule 
Table 7-1, Table 7-2 and Table 7-3. 
7.12.1 
Physician’s global assessment of psoriasis severity 
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 7-5. The PGA assessment will represent the average lesion 
severity on scalp, trunk and limbs (excluding face, genitals, and intertriginous areas). 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 7-5 
Physician’s Global Assessment (PGA) 
Score 
Grade 
Definition 
0 
Clear 
Plaque thickening = no elevation or thickening of normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red colouration but post-inflammatory 
hypo or hyperpigmentation may be present) 
1 
Almost 
clear 
Plaque thickening = none or possible thickening but difficult to ascertain 
whether there is a slight elevation above normal skin level 
Scaling = none or residual surface dryness and scaling 
Erythema = light pink colouration 
2 
Mild 
Plaque thickening = slight but definite elevation 
Scaling = fine thin scales partially or mostly covering lesions 
Erythema = light red colouration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = coarse scale layer at least partially covering most lesions 
Erythema = definite red colouration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with hard or 
sharp edges 
Scaling = non-tenacious or thick tenacious scale predominates, covering most 
or all of the 
lesions 
Erythema = very bright red colouration, extreme red coloration or deep red 
coloration 
 
7.12.2 
Body surface area involvement of psoriasis vulgaris 
The investigator or designee will assess the extent of the subject’s psoriatic involvement on the 
scalp, trunk and limbs (excluding face, genitals, and intertriginous areas).  
The total psoriatic involvement on the scalp, trunk and limbs 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. If the subject has psoriasis of guttatae character, 
these elements will be part of the estimation of total psoriatic involvement. The purpose of this is 
to obtain an estimate of the area on the trunk and limbs to be treated with trial medication. 

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7.12.3 
Local skin reactions 
The local skin reaction assessment 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:  
• 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 7-6. 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 7-6 and the subject will tell which one to mark.  
Signs and symptoms fulfilling the adverse advent definition should be reported as adverse 
events. 

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Table 7-6 
Local Skin Reaction Scores 
Investigator assessment of the lesional area 
 
0 (absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erosion/ulceration 
in lesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
Vesicles 
in lesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Investigator assessment of the perilesional area 
 
0=absent 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erythema  
in perilesional area 
None 
Barely visible 
erythema 
Distinct erythema 
Dark red erythema 
Scaling 
in the perilesional area 
None 
Barely visible 
scaling 
Distinct scaling 
Gross  scales 
Edema 
in perilesional area 
None 
 barely palpable 
swelling 
Easily palpable 
swelling 
Gross swelling 
Atrophy 
in perilesional area 
None 
Barely visible 
thinning 
Distinct thinning 
Striae 
Vesicles  
in perilesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Erosion/ulceration 
in perilesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
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 lasts 
for up to an hour 
Pronounced and 
lasts for several 
hours  
 
7.13 
Adverse Events 
7.13.1 
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 and first trial-related activity performed until the end of the study. An 

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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. 
7.13.2 
Timing 
AEs will be collected/assessed during the period from the time of the signature of the informed 
consent form by the subject and first trial-related activity performed.  
7.13.3 
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. 

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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). 
7.13.4 
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 
7.13.5 
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 
MC2-01 Investigator’s Brochure (for MC2-01 cream)26 or Taclonex® Ointment prescribing 
information27 (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. 
 
 
 

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7.13.6 
Trial medication overdose 
An overdose of the investigational product, i.e., a dose that is higher than the highest dose under 
clinical investigation or the known therapeutic dose, will be fully documented even if no toxic 
effects were observed and will be considered an AE. 
The maximum weekly dose of the MC2-01 cream and the comparator is 100 g. 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. 
7.13.7 
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.  
7.13.8 
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  
The death of a subject enrolled in a trial is per se not an event, but an outcome. Any event resulting 
in a fatal outcome must be fully documented and reported, regardless of the causality relationship 
to the IP. 
Any medical important events that may not result in death, be life-threatening, or require 
hospitalisation may be considered an SAE when, based on appropriate medical judgment, they 
may jeopardise the subject or the subject may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definitions.  

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Any pre-planned hospitalisations 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 Brochure1 or Taclonex® Ointment prescribing 
information,3, and for which there is evidence to suggest a causal relationship between the drug 
and the SAE. The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) will be 
informed of SUSARS according to local requirements. All investigators participating in the trial 
will also be notified of unexpected SAEs. The sponsor will report SAEs and other events 
requiring expedited reporting to regulatory authorities as required.  
Investigator instructions for reporting SAEs are provided in Section 13.2. 
7.14 
Unscheduled Visit 
An unscheduled visit may be performed at any time during the trial if judged necessary by the 
Investigator, such as for a severe reaction, suspected pregnancy, clinically significant AE, or 
clinically significant local skin reaction result. Details of the event are to be recorded in the 
subject’s records. 
7.15 
Follow-up Visit 
A follow-up visit is required for the following reasons:  
• 
Unresolved related AEs. 
For subjects assigned to the MC2-01 cream: 
• 
If the albumin-corrected serum calcium was above the normal reference range at Week 4 and 
Week 8 a repeat should be done 14 days (± 2 days) after.  
• 
If the HPA axis suppression is noted at Week 8 an ACTH challenge test should be performed 
28 days (± 2 days) after. 
7.16 
Early Termination 
If a subject withdraws from the trial prior to Week 4 and for subjects assigned to the MC2-01 
cream prior to Week 8, the subject is to return to the site for an unscheduled visit. The following 
procedures should be performed:  
• 
Collect all trial materials from the subject. 

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• 
Assess compliance 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Record any AEs. 
• 
Physical examination and vital signs   
• 
Perform a UPT for females of childbearing potential. 
• 
ECG (only for subjects assigned to the MC2-01 cream) 
• 
Haematology, biochemistry, and urinalysis.  
• 
PGA 
• 
BSA 
• 
Psoriasis Treatment Convenience Scale (Only if before Week 4) 
 
8.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
STATISTICAL AND ANALYTICAL PLANS 
8.1 
General Considerations for Data Analysis 
The methodology presented below represents a brief overview of the statistical methods that will 
be fully detailed in the statistical analysis plan (SAP). The SAP will be finalised before the 
database is locked. Any changes to the methods described in the final SAP will be described and 
justified in the clinical trial report. All statistical analyses will be performed using SAS statistical 
software (Version 9.2 or higher).  
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. No imputation will be made for 
missing data. 
8.2 
Sample Size and Power Considerations 
The choice of sample size in this trial is not based on statistical considerations, but rather on 
regulatory considerations with respect to common practice in maximum use studies evaluating 
pharmacokinetic profiles and evidence of HPA safety. The chosen number of approximately 25 
subjects included in the PK population at Week 4 in each treatment arm is considered sufficient 
to compare the PK properties corresponding to the two treatments. 
8.3 
Analysis Populations 
The analysis populations are defined as follows:  
• PK population: all subjects in the Safety population who have received the planned 
application of treatment at the Week 4 or Week 8 visit, respectively, and have had at least 
one post-application blood draw for PK assessment at the corresponding visit. 

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• Safety population: all subjects who are randomized and have been dispensed the trial 
medication at Randomisation/Day 0, excluding subjects who return all of the trial 
medication unopened. The Safety population will be used for all safety analyses other than 
evaluation of the HPA-axis.  
• HPA population: all subjects in the Safety population that are assigned to MC2-01 cream 
and who show normal HPA function at Baseline.  Since the objective of the analysis is to 
estimate the risk to subjects with normal HPA function of HPA-axis suppression following 
treatment, subjects who meet the definition of HPA-axis suppression at Baseline will be 
excluded from the analysis. The HPA population will be used for the HPA axis suppression 
analysis. 
8.4 
Background and Demographic Characteristics 
Descriptive statistics will be used to summarise demographic characteristics (age, sex, and race) 
and background characteristics for the Safety population.  Past/coexistent medical history 
information, physical examination observations, and vital signs information for all randomised 
subjects will be presented in a by-subject listing.   
8.5 
Trial Medication/Exposure 
Descriptive statistics will be used to summarise trial medication exposure for the Safety 
population.  Measures of trial medication exposure will include the total duration of treatment, the 
total weight of trial medication used, and the total number of applications.   
8.6 
Prior and Concomitant Therapy 
Prior and concomitant medication information for all randomised subjects will be presented in a 
by-subject listing.   
8.7 
Analysis of Pharmacokinetics 
All available concentration results will be summarised using appropriate descriptive statistics for 
active ingredients (BDP and CAL) and for their major metabolites. Median and individual 
concentration versus time curves will be plotted (linear and semi-log plots). 
Plasma PK parameters (AUC0-t, AUC0-∞, AUC0-7, Cmax, Tmax, and T½) will be calculated at Week 4 
and Week 8 (subjects randomised to MC2-01 cream only). The PK parameters AUC0-7 and Cmax 
will be calculated using standard formulas inserting the lower limit of quantification for non-
quantifiable levels of the analyte; therefore, AUC0-7 will be an upper limit in case at least one time 
point shows a non-quantifiable level of the analyte, and Cmax will be an upper limit in case all time 
points show non-quantifiable levels of the analyte. For a given analyte, the PK parameters AUC0-t, 
AUC0-∞, Tmax, and T½ will be calculated if data allow. The PK parameters will be summarised 
using appropriate descriptive statistics including median, lower and upper quartiles, minimum and 
maximum. 

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Assessment of systemic exposure (Week 4) 
Assessment of relative systemic exposure in the two treatment arms will be performed for AUC0-7 
and Cmax at Week 4. It will be based on an analysis of variance for censored data for each 
parameter, assuming a log-normal distribution of the PK parameter. Geometric mean ratio and 
associated 90% confidence interval will be presented.  
8.8 
Analysis of Safety 
The assessment of HPA axis suppression (using pre- and post-stimulation cortisol levels) and of 
changes in calcium metabolism are the primary safety endpoints in this trial. 
Other assessments of safety will be based mainly on the frequency of AEs and on the number of 
laboratory values that fall outside of predetermined ranges, presented for the two periods, Weeks 
1 to 4 and Weeks 5 to 8, separately. Adverse events will be presented in data listings and 
summarized by frequency and severity for each treatment group for each period.  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. 
8.8.1 
HPA-axis suppression 
The number and proportion of subjects with HPA-axis suppression at Week 4 and Week 8 will be 
summarised.   
8.8.2 
Calcium metabolism endpoints 
Summary statistics will be provided for the following:  
Observed values of and changes from Baseline to Week 4 and Week 8 in: 
– Albumin-corrected serum calcium 
– 24 hours urinary calcium excretion 
– Ratio of urinary calcium to creatinine 
8.8.3 
Adverse events 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
terminology.  Treatment-emergent adverse events will be summarized by the overall incidence of 
at least one event, incidence by body system, and incidence by body system and preferred term.  
Each subject will contribute only once (e.g., the first occurrence) to each of the rates, regardless of 
the number of occurrences (events) the subject experiences.  Treatment-emergent AEs will be 
summarised by severity (mild, moderate, or severe), and by relationship to trial product (none, 
unlikely, possible, probable, or definite). An adverse event is treatment-emergent if its date of 
onset is Day 1 (Baseline) or later. 

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Discontinuations from the trial due to AEs and SAEs will be listed by subject. 
8.8.4 
Other safety variables 
Clinical laboratory values will be reported as complete listings of individual subject data.  
Clinical laboratory data will be summarized 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, SDs, ranges), and by the flagging of 
notable values in data listings. 
Data from other tests (e.g., vital signs, ECG results) 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. 
Vital signs will be summarised at each visit, both as absolute values and as change from Baseline, 
with descriptive statistics. 
8.9 
Analysis of Other Endpoints 
8.9.1 
Physician global assessment 
Investigator ratings of disease severity will be summarised by trial visit using frequency counts 
for each treatment. The proportion of subjects with treatment success, defined as a minimum 2-
point decrease from Baseline in the physician’s global assessment (PGA) on the trunk, limbs, 
and scalp will be summarized. 
8.9.2 
Psoriasis treatment convenience scale 
Subject assessment of treatment convenience at Week 4 using a Psoriasis Treatment Convenience 
Scale will be summarized and further compared between MC2-01 cream and the active comparator 
using mixed effect model with treatment as a systematic effect and study site as a random effect. 
8.10 
Quality of Life Analysis (Not Applicable) 
Not applicable. 
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 

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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 
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.  

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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 
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. 

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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.  
12.4 
Disclosure and Confidentiality 
12.4.1 
Confidentiality of trial documentation 
By signing the protocol, the investigator agrees to keep all information provided by the sponsor in 
strict confidence and to request similar confidentiality from his/her staff and the IRB or IEC. Trial 
documents provided by the trial sponsor (i.e., protocols, Investigators' Brochures, eCRFs and other 
material) will be stored appropriately to ensure their confidentiality. The information provided by 
the sponsor to the investigator may not be disclosed to others without direct written authorisation 
from the sponsor, except to the extent necessary to obtain informed consent from subjects who 
wish to participate in the trial. 
12.4.2 
Privacy of individual health information  
The investigator will undertake to protect the privacy of all individually identifiable health 
information except as specifically authorised by each individual subject through the written 
informed consent. The Informed Consent document will include a request of the subject’s consent 
to release the collected data for research purposes in such a way that the individual’s identity 
remains masked. While all data records will be identified by the corresponding subject number, 
the identity of the subject will be held in confidential source documents at the trial site. All trial 
personnel with access to this information are legally bound not to disclose such information. 

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13.0 
EMERGENCY PROCEDURES 
13.1 
Emergency Unblinding (Not Applicable) 
This is an open-label trial. 
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.clinicaltrials.gov and in accordance with 
applicable regulations.  
All publications (e.g., manuscripts, abstracts, oral/slide presentations, book chapters) based on this 
trial must be submitted to MC2 for review, as specified in the Clinical Trial Agreement between 
the institution, investigator and MC2 or its designee. 
 
 

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16.0 
REFERENCES 
 
(1) 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) 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. 
 
(13) 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. 

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(14) 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. 
 
(15) 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. 
 
(16) 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. 
 
(17) Samarasekera E, Sawyer L, Parnham J, Smith CH. Assessment and management of 
psoriasis: summary of NICE guidance. BMJ 2012;345:e6712. 
 
(18) 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. 
 
(19) 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. 
 
(20) Selby PL, Davies M, Marks JS, Mawer EB. Vitamin D intoxication causes hypercalcaemia 
by increased bone resorption which responds to pamidronate. Clin Endocrinol (Oxf) 
1995;43:531-536. 
 
(21) Bourke J, Berth-Jones J, Iqbal SJ, Hutchinson P. High-dose topical calcipotriol in the 
treatment of extensive psoriasis vulgaris. Br J Dermatol 1993;129:74-76. 
 
(22) Matkovic V, Ilich JZ, Andon MB et al. Urinary calcium, sodium, and bone mass of young 
females. Am J Clin Nutr 1995;62:417-425. 
 
(23) O'Brien KO, Abrams SA, Stuff JE, Liang LK, Welch TR. Variables related to urinary 
calcium excretion in young girls. J Pediatr Gastroenterol Nutr 1996;23:8-12. 
 
(24) 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. 
 
(25) Amphastar Pharmaceuticals I.  CortrosynTM US Prescribing Information.  2005.  
 
(26) MC2 Therapeutics. Investigational Brochure, version 3, 2017.  2017.  
 
(27) FDA. Taclonex® Ointment Prescribing Information.  2017. 
 

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17.0 
APPENDICES 
 
17.1 
Appendix 1 Contact List of MC2 and Protocol Authors  
Contact details for MC2 representatives are provided to the trial sites on a list outside the protocol, 
which is included in the clinical trial application.  
Sponsor 
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
c/o Agern Alle 24-26 
2970 Hoersholm 
DENMARK 
(“MC2”) 
 
Protocol Author 
Barbara Liptak, Medical Writer, Novella Clinical, 350 West Passaic Street, Suite 550, Rochelle 
Park, NJ 07662. 
Johan Selmer, VP Medical Affairs, MC2 Therapeutics 
Birgitte Vestbjerg, Director Clinical Operation, MC2 Therapeutics 
Carol Udell, Senior Director, Clinical Data, Management and Biostatistics, Novella Clinical, 
350 West Passaic Street, Suite 550, Rochelle Park, NJ 07662. 
 
 
 
 

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17.2 
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. 
 
ICON Laboratory Services Inc., 8282 Halsey Road, Whitesboro, NY 13492 USA. ICON will be 
responsible for the PK analysis. 
 
 
 
 
 
 
 
 
 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Approval Form 
 
Protocol MC2-01-C3  
 
 
CLINICAL TRIAL PROTOCOL APPROVAL FORM  
Product: MC2-01 (calcipotriene/betamethasone dipropionate) Cream 
Protocol number: MC2-01-C2 
Protocol title: 
A Randomised, Multicentre, Open-label, Parallel-group Maximal Use Trial, 
Evaluating the Pharmacokinetic Profile of the Active Ingredients and their 
Metabolites after application of MC2-01 Cream compared with Active 
Comparator in Subjects with Extensive Psoriasis Vulgaris 
Version: 3.0 
Date: 20 December 2017 
 
The following person has approved this clinical trial protocol: 
 
Carol Udell 
Senior Director, Clinical Data 
Management and Biostatistics 
Novella                                              _________________________________________   
                                                                                            Signature and date 
 
 
21-Dec-2017 | 10:36:14 EST