A Multicentre, Open-label, Single-group Maximal Use Trial, Evaluating the Safety and Pharmacokinetic Profile of the Active Ingredients and Their Metabolites After Application of MC2-01 Cream in Adolescents With Extensive Psoriasis Vulgaris
Phase: PHASE2
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics

MC2 Therapeutics 
 
Protocol MC2-01-C6 
23 September 2018 
 
Clinical Trial Protocol 
 
Trial Title: 
A Multicentre, Open-label, Single-group Maximal Use 
Trial, Evaluating the Safety and Pharmacokinetic Profile of 
the Active Ingredients and their Metabolites after 
application of MC2-01 Cream in Adolescent Subjects  
(age 12 to 16 years, 11 months) with Extensive Psoriasis 
Vulgaris 
 
 
Investigational product: 
MC2-01 (calcipotriol and betamethasone dipropionate,  
50 micrograms/0.64 mg/g) Cream 
 
Protocol No: 
MC2-01-C6 
 
IND: 
127152 
 
EudraCT No: 
2018-000685-12 
 
Development phase: 
2 
 
Documents status: 
Final 
 
Document version: 
Version 5.0 
 
Document date:  
23 September 2018 
 
  
 
 
 
 
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-C6 
23 September 2018 
 
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CLINICAL TRIAL PROTOCOL APPROVAL 
Product: MC2-01 (calcipotriol/betamethasone dipropionate) cream 
Protocol number: MC2-01-C6 
Protocol title: A Multicentre, Open-label, Single-group Maximal Use Trial, Evaluating the 
Safety and Pharmacokinetic Profile of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream in Adolescent Subjects (age 12 to 16 years, 11 months) with 
Extensive Psoriasis Vulgaris. 
The following persons has approved this clinical trial protocol. Separate signature page is 
adjoined to this document. 
 
Johan Selmer, MD, VP Medical Affairs, MC2 Therapeutics 
Charlotte Hindsberger, Principal consultant, Biostatistics, S-cubed 
Andreas Pinter, Director Clinical Research, Dept. of Dermatology, Venereology and 
Allergology, Frankfurt, Germany 
 
 
 

MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C6 
23 September 2018 
 
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SIGNATURE PAGE FOR INVESTIGATOR(S) 
 
Product: MC2-01 (calcipotriol/betamethasone dipropionate) cream 
Protocol number: MC2-01-C6 
Version: 5.0 
Protocol title: A Multicentre, Open-label, Single-group Maximal Use Trial, Evaluating the 
Safety and Pharmacokinetic Profile of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream in Adolescent Subjects (age 12 to 16 years, 11 months) 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-C6 
23 September 2018 
 
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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 ..............................................................................................................13 
2.1 
Background ..............................................................................................................13 
2.2 
Rationale of the Trial ................................................................................................14 
2.3 
Benefit-risk Assessment ...........................................................................................16 
3.0 
TRIAL OBJECTIVES AND PURPOSE ..........................................................................17 
4.0 
TRIAL DESIGN .................................................................................................................17 
4.1 
Overall Trial Design .................................................................................................17 
4.2 
Trial Endpoints .........................................................................................................19 
5.0 
SELECTION OF TRIAL POPULATION .......................................................................20 
5.1 
Subject Population ....................................................................................................20 
5.2 
Inclusion Criteria ......................................................................................................20 
5.3 
Exclusion Criteria .....................................................................................................21 
5.4 
Withdrawals and Discontinuation of Treatment ......................................................23 
5.5 
Replacement Policy ..................................................................................................24 
6.0 
TRIAL TREATMENTS ....................................................................................................25 
6.1 
Investigational Product .............................................................................................25 
6.2 
Dosing Regimen .......................................................................................................25 
6.3 
Dose Modification ....................................................................................................26 
6.4 
Packaging, Labeling, Storage and Destruction ........................................................26 
6.5 
Assignment to Treatment .........................................................................................26 
6.6 
Prior, Concomitant, and Prohibited Therapy ...........................................................26 
6.6.1 
Washout of prohibited medications prior to enrolment ...............................27 
6.6.2 
Prohibited medications during the trial ........................................................27 
6.6.3 
Allowed treatment on the face, skin folds, and genital skin only ................27 
6.7 
Treatment Compliance .............................................................................................27 
7.0 
VISIT SCHEDULE AND ASSESSMENTS .....................................................................28 
7.1 
Demographics and Medical History .........................................................................32 
7.2 
Prior and Concomitant Medication ..........................................................................32 

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7.3 
Physical Examination ...............................................................................................32 
7.4 
Vital Signs ................................................................................................................33 
7.5 
Pregnancy Test .........................................................................................................33 
7.6 
Laboratory Assessments ...........................................................................................33 
7.6.1 
Hematology and biochemistry .....................................................................33 
7.6.2 
HPA axis suppression/ ACTH challenge test ...............................................34 
7.6.3 
Food diary: calcium-rich nutrients ...............................................................34 
7.6.4 
Analysis of Morning Urine Spot Samples ....................................................35 
7.6.5 
Pharmacokinetics .........................................................................................35 
7.7 
Electrocardiogram ....................................................................................................36 
7.8 
The Psoriasis Treatment Convenience Scale ...........................................................36 
7.9 
Investigator Assessments .........................................................................................36 
7.9.1 
Physician’s global assessment of psoriasis severity .....................................36 
7.9.2 
Body surface area involvement of psoriasis vulgaris ...................................37 
7.9.3 
Local skin reactions ......................................................................................38 
7.10 
Adverse Events .........................................................................................................40 
7.10.1 
Adverse events assessments .........................................................................40 
7.10.2 
Timing ..........................................................................................................40 
7.10.3 
Severity of adverse events ............................................................................40 
7.10.4 
Relationship of an adverse event to trial treatment ......................................41 
7.10.5 
Unexpected adverse events ..........................................................................41 
7.10.6 
IP overdose ...................................................................................................42 
7.10.7 
Pregnancy .....................................................................................................42 
7.10.8 
Serious adverse event ...................................................................................42 
7.11 
Unscheduled Visit ....................................................................................................43 
7.12 
Follow-up Visit/ Follow-up Telephone Call ............................................................43 
7.13 
Early Termination ....................................................................................................44 
8.0 
STATISTICAL METHODS AND DETERMINATION OF SAMPLE SIZE 
STATISTICAL AND ANALYTICAL PLANS ...............................................................44 
8.1 
General Considerations for Data Analysis ...............................................................44 
8.2 
Sample Size and Power Considerations ...................................................................45 
8.3 
Analysis Populations ................................................................................................45 
8.4 
Background and Demographic Characteristics ........................................................45 
8.5 
Trial Medication/Exposure .......................................................................................45 
8.6 
Prior and Concomitant Therapy ...............................................................................45 

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8.7 
Analysis of Pharmacokinetics ..................................................................................45 
8.8 
Analysis of Safety ....................................................................................................46 
8.8.1 
HPA-axis suppression ..................................................................................46 
8.8.2 
Calcium metabolism endpoints ....................................................................46 
8.8.3 
Adverse events .............................................................................................46 
8.8.4 
Other safety variables ...................................................................................47 
8.9 
Analysis of Other Endpoints ....................................................................................47 
8.9.1 
Physician global assessment .........................................................................47 
8.9.2 
Psoriasis treatment convenience scale ..........................................................47 
8.10 
Quality of Life Analysis (Not Applicable) ...............................................................47 
9.0 
CHANGES IN THE PLANNED TRIAL .........................................................................47 
9.1 
Protocol Amendments ..............................................................................................47 
9.2 
Termination or Suspension of the Trial ....................................................................48 
10.0 DATA HANDLING AND RECORD KEEPING ............................................................48 
10.1 
Recording of Data ....................................................................................................48 
10.1.1 
Source documents ........................................................................................48 
10.1.2 
Case report forms .........................................................................................49 
10.2 
Retention of Documents ...........................................................................................49 
11.0 QUALITY CONTROL AND QUALITY ASSURANCE ...............................................49 
11.1 
Direct Access to Source Documents ........................................................................49 
11.2 
Monitoring Procedures .............................................................................................49 
11.3 
Audit and Inspection ................................................................................................49 
12.0 ETHICS ...............................................................................................................................50 
12.1 
Ethical Conduct of the Trial .....................................................................................50 
12.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) ...........50 
12.3 
Subject Information and Consent .............................................................................50 
12.4 
Disclosure and Confidentiality .................................................................................50 
12.4.1 
Confidentiality of trial documentation .........................................................50 
12.4.2 
Privacy of individual health information .....................................................50 
13.0 EMERGENCY PROCEDURES .......................................................................................51 
13.1 
Emergency Unblinding (Not Applicable) ................................................................51 
13.2 
Reporting of Serious Adverse Events and Pregnancies ...........................................51 
13.2.1 
Contact person(s) and number(s) .................................................................51 
13.2.2 
Reporting procedures ...................................................................................51 

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14.0 INSURANCE ......................................................................................................................51 
15.0 PUBLICATION POLICY .................................................................................................52 
16.0 REFERENCES ...................................................................................................................53 
17.0 APPENDICES ....................................................................................................................56 
17.1 
Appendix 1  Contact List of MC2 and Protocol Authors .........................................56 
17.2 
Appendix 2  Vendors ................................................................................................57 
 
LIST OF TABLES 
Table 7-1 Visit Schedule and Assessments .................................................................................28 
Table 7-2 Fitzpatrick Skin Type Classification ..........................................................................32 
Table 7-3 Physician’s Global Assessment (PGA) ......................................................................37 
Table 7-4 Local Skin Reaction Scores ........................................................................................39 
 
LIST OF FIGURES 
Figure 4-1  Trial Design ................................................................................................................18 
 
 
 

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Clinical Trial Protocol 
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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 
AR 
Adverse Reaction 
AUC0-t 
Area under the time-concentration curve from time zero to the last 
measurable concentration 
AUC0-5 
Area under the time-concentration curve from time zero to 5 hours imputing 
the lower limit of quantification (LLoQ) for concentrations below LLoQ 
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 
CYP 3A4 
Cytochrome P450 3A4  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
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 
LLoQ 
Lower Limit of Quantification 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MUsT 
Maximal Usage Trial 
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 

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Abbreviation 
Definition 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
SV1, SV2 
Screening Visit 1, Screening Visit 2 
Tmax 
Time to maximum plasma drug concentration 
UBC  
United BioSource Corporation 
US  
United States 
UVB 
Ultraviolet B 
WBC 
White blood cell 
 

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Clinical Trial Protocol 
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1.0 
SYNOPSIS 
Trial Title: 
A Multicentre, Open-label, Single-group Maximal Use Trial, Evaluating the 
Safety and Pharmacokinetic Profile of the Active Ingredients and their 
Metabolites after application of MC2-01 Cream in Adolescent Subjects (age 12 
to 16 years, 11 months) with Extensive Psoriasis Vulgaris 
Protocol Number: 
MC2-01-C6 
Sponsor:  
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
 
Development Phase: 
2 
Trial Objectives: 
The primary objectives are 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. 
The secondary objective is to evaluate the pharmacokinetic profile of the active 
ingredients and their main metabolites following once daily topical application 
of MC2-01 cream under maximum-use conditions in adolescent subjects (age 12 
to 16 years, 11 months) with extensive psoriasis vulgaris. 
Trial Design: 
This is a phase 2, open-label, single-group, multicentre trial in which the 
investigational product, MC2-01 cream, is investigated in adolescent subjects 
(age 12 to 16 years, 11 months) with clinically diagnosed extensive psoriasis 
vulgaris.  
After written informed assent/consent is obtained the subjects will undergo 
screening procedures. For subjects requiring a washout period, informed assent/ 
consent must be completed prior to washout. Subjects that fulfil the inclusion 
and exclusion criteria will be treated with the MC2-01 cream once-daily for 8 
weeks.  
At Week 4 and Week 8, the effect of once-daily use of MC2-01 cream on the 
HPA axis and the calcium metabolism will be evaluated. Other assessments 
(local skin reactions, AEs, laboratory tests, electrocardiogram (ECG), vital signs 
and physical examination) and efficacy assessments are also performed. At 
Week 4, the pharmacokinetic (PK) profile of calcipotriol (CAL), betamethasone 
dipropionate (BDP) and their main metabolites MC1080 and betamethasone 17-
propionate, respectively, will be assessed. 
The maximum trial duration for each subject will be approximately 18 weeks 
and includes a screening period of up to 6 weeks (if washout of medication is 
required), a treatment period of 8 weeks, and a follow-up period of up to 4 weeks. 
 
 

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Clinical Trial Protocol 
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Planned Sample Size: 
It is planned to enrol approximately 30 subjects. The choice of sample size in 
this trial is based on regulatory considerations with respect to common practice 
in maximum use studies. For the PK population, the aim is to have at least 20 
subjects included that have at least completed Week 4 (Visit 3). 
Trial Population: 
Generally healthy males or non-pregnant females, between 12 to 16 years, 11-
month-old, 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 scalp and body (trunk and/or limbs) and a 
treatment area between 10% and 30% of the body surface area (BSA), excluding 
psoriatic lesions on the face, genitals, and intertriginous areas. 
Investigational Product(s): 
MC2-01 cream (CAL and BDP, 50 micrograms/0.64 mg/g).  
Reference Product(s): 
Not applicable. 
Pharmacokinetics Evaluation 
Criteria: 
Blood samples for PK assessments will be collected at 
• 
SV2: single time point  
• 
Week 2 visit: single time point before IP application  
• 
Week 4 visit: before the planned IP application at the visit and then at 
1, 3, and 5 hours after the application 
• 
Week 8 visit: single time point. Subject should not apply IP on the day 
of the Week 8 visit  
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: 
The endpoint for the HPA axis evaluation will be a serum cortisol level of less 
than 18 µg/dL at 30 minutes after Adrenocorticotropic hormone (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; 
• 
Ratio of urinary calcium to creatinine. 
Other Safety Evaluation 
Criteria 
Adverse event incidence and severity, laboratory test results (haematology, 
clinical chemistry), vital signs, ECG, local skin reactions, physical 
examination.  
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. 
 

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Primary endpoint: 
HPA axis suppression: The proportion of subjects with HPA-axis suppression at 
Week 4 and Week 8 will be summarised using frequency counts.   
Calcium metabolism: 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 
– 
Ratio of urinary calcium to creatinine (spot analysis, second morning urine 
sample) 
Secondary Endpoints: 
Plasma PK parameters (AUC0-t, AUC0-5, Cmax, and Tmax) will be calculated at 
Week 4. The PK parameters AUC0-5 and Cmax will be calculated using standard 
formulas inserting the lower limit of quantification for non-quantifiable levels 
of the analyte; therefore, AUC0-5 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 and Tmax will be calculated if at least 
one time-point shows a quantifiable level of the analyte. The PK parameters will 
be summarised using appropriate descriptive statistics including median, lower 
and upper quartiles, minimum and maximum. 
A parametric model will be applied to estimate the geometric mean of Cmax and 
AUC0-5, respectively. The log-transformed values of the PK parameters will be 
assumed to be normally distributed. The mean of this normal distribution will be 
estimated taking the potential censoring of the values into account.  The mean 
will then be back-transformed to the original scale as the geometric mean. 
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). 
Other safety endpoints: Adverse events will be presented in data listings and 
summarised by frequency and severity. Laboratory, ECG, and vital sign data will 
be presented in data listings. Abnormal ECG and laboratory findings will be 
presented 
Trial Sites: 
Approximately 12 sites in Europe 
Planned Dates of Trial: 
Q4 2018 – Q4 2020 

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2.0 
INTRODUCTION   
2.1 
Background 
Psoriasis is a common condition that affects about 3.5% of the US population (1) and 2.5% of the 
German population (2). Epidemiological studies from other countries have presented prevalence 
data that have been much higher or lower, but the very different methodologies used in published 
studies makes it difficult to compare or draw conclusions about any geographical differences (3). 
Several prevalence studies have demonstrated that approximately one-third of psoriatic patients 
develop their symptoms sometimes during childhood (4, 0).  
A recent, thorough epidemiological study by Tollefson et al. (6) has demonstrated that the 
incidence of psoriasis increases steadily with age until approximately the 7th decade of life, with 
a more rapid increase in the incidence until age 30-35. Furthermore, an increase in incidence of 
psoriasis was observed throughout the study period from 1970 to 2000. Overall annual incidence 
in the pediatric population was 29.6 per 100.000 in 1970-1974, 42.6 per 100.000 in 1985-1989, 
and 62.7 per 100.000 in 1995-1999. This temporal trend is very similar to the trend seen in adults 
during the same time period (7). The prevalence of adolescents diagnosed with psoriasis in the age 
group 12-17 years can be calculated to up to 0.72% (age and sex adjusted to the 2000 US 
population) from incidence data presented by Tollefson (6). 
Plaque psoriasis with its variants is the most frequent type, also in infants and childhood. In a large 
series of more than 1200 Australian patients, 34% of the children presented this type of psoriasis 
manifestation (8). Lesions typically consist of well-defined, erythematous papules and scales of 
varying size with silvery scales. The lesions have close resemblance to those seen in adult patients 
(4, 0). 
It is well known that psoriasis in adults often are associated with comorbidities resulting in high 
cardiovascular morbidity (10-12). Also, children suffering from psoriasis seem to have a higher 
prevalence of comorbidities, including obesity, hyperlipidaemia, diabetes mellitus, hypertension, 
rheumatoid arthritis, and Crohn’s disease (2, 13-16)). In addition to comorbidities with effect on 
cardiovascular disease, pediatric patients with psoriasis have also reported to have an increased 
risk of anxiety, depression, and other psychiatric disorders (17). Because of the burden of disease 
and the associated comorbidities, early diagnosis and management in children are essential. 
Considering the many similarities – both related to pathophysiology, clinical presentation, and 
concomitant diseases – it is not surprising that most therapeutics effective in adult psoriasis are 
equally effective in pediatric psoriasis. Despite this, treatment of childhood psoriasis is often 
considered a therapeutic challenge. Various therapies are available, but only a limited number of 
trials have studied the use of anti-psoriatic agents in children. Furthermore, many treatments are 
not approved for use in children and guidelines are often missing for children and adolescents. 

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There is no cure for psoriasis. The goal of treatment of both adult and childhood psoriasis is to 
reduce or eliminate its signs and symptoms. Mild to moderate disease is often treated with topical 
therapies. Among topical therapies, a combination treatment of a Vitamin D analog and a topical 
glucocorticosteroid has become especially popular. Several studies show that the combination of 
Calcipotriol (CAL) and Betamethasone dipropionate (BDP) is superior to each of the single agents 
(18,19). There is strong scientific rationale for the combination of vitamin D and 
glucocorticosteroids both with respect to efficacy and safety (20-22), and combination treatment 
with a Vitamin D analog and a topical corticosteroid is recommended in both American and 
European guidelines (23-26). The CAL/BDP products Taclonex® Ointment and Taclonex® scalp 
solution is approved for use in the age group 12-17 years in the US. The CAL/BDP products are 
marketed as Daivobet® Ointment and Gel respectively in the EU. Clinical trials with combinations 
of CAL and BDP are not possible in children below the age of 12, due to the BDP component.     
CAL and BDP are incompatible in an aqueous environment, since CAL requires basic conditions 
to maintain stability while betamethasone requires acidic conditions. Currently marketed products 
are therefore restricted to non-aqueous, oil-based formulations. 
Sponsor (referred to as MC2 in remainder of the protocol) has developed the MC2-01 cream 
containing the fixed dose combination 50 micrograms CAL (as anhydrate) and 0.64 mg/g BDP 
using the proprietary PADTM Technology which protects the drug substances from degradation 
during storage. The MC2-01 cream is easy to apply, and the cosmetic appearance is that of a white, 
easily-spreadable cream that absorbs completely into the skin a few minutes after application and 
it is expected that MC2-01 cream will differentiate from marketed formulations of CAL/BDP by 
patient preference for the cream. 
2.2 
Rationale of the Trial 
MC2-01 cream is investigated following once daily topical application under maximum-use 
conditions in Adolescent Subjects (age 12 to 16 years, 11 months) with clinically diagnosed 
extensive psoriasis vulgaris of at least moderate disease severity.  
Subjects in this trial will have psoriasis on the body (trunk and/or limbs), and with or without scalp 
involvement that is at least moderate in severity according to PGA and involves 10-30% of BSA, 
excluding face, genitals and intrigenous areas. This disease extent is at the limit where topical 
treatment would be used, and systemic therapy or phototherapy would be considered.  
At Week 4, the PK profile of CAL, BDP and their main metabolites MC1080 and betamethasone 
17-propionate, respectively, will be assessed. Blood samples will be taken at selected intervals 
after topical dosing of each trial medication. The following PK parameters will be calculated: area 
under the concentration-time curve (AUC) from time zero to the planned last PK blood sampling 
time point of 5 hours (AUC0-5), maximum plasma drug concentration (Cmax), and time to 
maximum plasma drug concentration (Tmax).  

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At Week 4 and Week 8, the effect of once-daily use of MC2-01 cream on the HPA axis and the 
calcium metabolism will be evaluated. 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.  
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 trial, enrolled subjects will be subjected to an 
ACTH-challenge test before and after 4 and 8-week treatment.  
It is well known that safety analysis of oral or topical medication containing vitamin D or 
analogues hereof include an evaluation of effect on calcium metabolism. Generally, analysis of 
calcium in a 24-h urine collection is considered to be the most reliable method for evaluation of 
changes in calcium homeostasis. This method is not well accepted by many patients, and the low 
adherence to 24-h urine collection means that results of this test often are unreliable (27). A 
number of papers have presented data to suggest that a spot calcium/creatinine test may 
substitute for 24-hour urine calcium collection (28-30) Spot  calcium/creatinine tests may be 
done on random urine samples, first morning urine, or second morning urine. For this trial, 
second morning urine is preferred, both because it is convenient in relation to time of visit, and 
because reference ranges of this test for adolescent is well documented. Both the 24-h urine 
sample collection and calcium/creatinine spot testing suffer from high intra-patient variability, 
and repeated samples is often recommended to improve accuracy of either test (31). For this 
reason, subjects with second morning calcium/creatinine spot test above the upper reference 
value at week 4 or week 8 must have this test repeated at the following visit. Moreover, if the 
calcium-creatinine ratio is above the reference range at two consecutive visits during the trial, 
24-hour urine collection will be performed. 
It is well-established that there is a relationship between dietary calcium intake and the urinary 
calcium excretion in adults (32). The urinary excretion of calcium has been reported to increase 
by 6-19 mg with each additional 100 mg of calcium intake (32, 33). Subjects will not be asked to 
change their diet during the trial, 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 4 days prior to each second morning urine collection. Considering that dairy 
products account for the majority of the 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 

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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 
within 4 weeks prior to Visit 1/Day 0 in this trial with the exception of stable doses of oral vitamin 
D (up to 400 IU/day) at baseline with no dose adjustment during the trial period. Systemic safety 
of MC2-01 cream on calcium metabolism and HPA axis will be assessed at Week 4 and Week 8. 
2.3 
Benefit-risk Assessment 
The subject population will be composed of adolescent subjects (age 12 to 16 years, 11 months) 
with psoriasis on the body (trunk and/or limbs), and with or without scalp involvement. The 
psoriasis disease intensity should be at least moderate in severity according to PGA and involve 
10-30% of BSA, excluding face, genitals and intertriginous areas, in order to evaluate the trial 
medication under maximum use conditions. 
Topical treatment with CAL/BDP is a well-known topical treatment for psoriasis. Daivobet® 
Ointment was approved in adults more than 15 years ago. Three different topical CAL/BDP 
formulations are approved in EU today for use in adults – all showing similar safety profiles with 
very limited systemic exposure 
According to the SmPC for Daivobet® Gel, the common adverse reaction (AR)E (>1%) is pruritus. 
Uncommon (i.e., ≥0.1% and <1%) ARs are folliculitis, skin infections, exacerbation of psoriasis, 
dermatitis, erythema, rash, skin irritation, skin burning sensation, application site pain, as well as 
eye irritation (probably related to use on scalp). Rare ARs (≤0.1%) are skin striae, skin exfoliations, 
hypersensitivity, and rebound effect. The ARs for Daivobet® Ointment are remarkably like what 
has been observed with Daivobet® gel. In the US both the Ointment and Gel of CAL/BDP are 
approved for use in adolescents; Taclonex® Ointment (body psoriasis) for 4 weeks and Taclonex® 
Topical Suspension (scalp psoriasis) for 8 weeks, and the US prescribing information does not 
distinguish between ARs seen in adults and adolescents. 
The description of the AR profile in the US prescribing information for Taclonex® Ointment and 
Taclonex® Topical Suspension does not differ from the description in the SmPCs for Daivobet® 
Ointment and Gel.   
The systemic safety (HPA and calcium metabolism) of Daivobet® Ointment in body psoriasis has 
been evaluation a 4-week uncontrolled maximal usage trial clinical trial in the pediatric population 
age 12 to 17 years, as well as in two uncontrolled open 8-week trials with Daivobet® Gel including 
in total 109 adolescents aged 12-17 years with scalp psoriasis. The ARs seen in these trials were 
few and mild and did not differ from what is described from studies in adults.  
 

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The benign safety profiles observed in these trials are not surprising. There is no indication that 
children are more sensitive to HPA axis suppression than adults and there is no increased 
sensitivity of Vitamin D in children. Furthermore, based on considerations on skin penetration (34) 
and BSA to body mass ratio in adolescent (35), treatment of adolescents with topical therapies will 
only result in marginal increases in systemic exposure compared to what is seen in adults.  
The fact that the AR profiles for Daivobet® Ointment and Gel are so similar despite treatment 
periods of 4 and 8 weeks, respectively, suggest that the nature of the ARs are independent of the 
length of treatment. This fact is underscored by the ARs in a trial where subjects were treated with 
the ointment for up to 52 weeks (36). Despite the prolonged treatment regime, there were no ARs 
not already mentioned for trials of shorter duration.  
MC2-01 cream contains the same active ingredients at identical concentrations of CAL and BDP 
as the marketed products in Europe and in the US but in a novel cream formulation that is expected 
to provide better cosmetic acceptability to patients than the currently available formulations. A 
cream formulation of CAL and BDP may benefit subjects by providing improved convenience and 
ease of use resulting in increased patient adherence to therapy which will improve real-life 
treatment outcome. 
3.0 
TRIAL OBJECTIVES AND PURPOSE 
The primary objectives are to evaluate the effect of MC2-01 cream on the HPA axis and calcium 
metabolism following once daily topical application under maximum-use conditions in subjects 
with extensive psoriasis vulgaris. 
The secondary objective is to evaluate the pharmacokinetic profile of the active ingredients and 
their main metabolites following once daily topical application of MC2-01 cream under 
maximum-use conditions in adolescent subjects (age 12 to 16 years, 11 months) with extensive 
psoriasis vulgaris. 
4.0 
TRIAL DESIGN 
4.1 
Overall Trial Design 
This is a phase 2, open-label, single-group, multicentre trial in which the investigational product 
(IP), MC2-01 cream, is investigated in adolescent subjects (age 12 to 16 years, 11 months) with 
clinically diagnosed extensive psoriasis vulgaris of at least moderate disease severity (according 
to the Physician’s Global Assessment of Disease Severity; PGA) on body (trunk and/or limbs), 
and with or without scalp involvement. 
After written informed assent is provided by the subject and written informed consent is provided 
by the parent(s) or legal guardian(s) and the consent document is signed by the investigator or 
designee the subjects will undergo screening procedures. For subjects requiring a washout period, 
informed assent/informed consent must be completed prior to washout. Prior to Screening Visit 2 

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(SV2) the subject (or the parent(s) or legal guardian(s)) is instructed to keep a diary for a 4-day 
registration of the daily intake of calcium-rich nutrients. At SV2, a second morning urine sample 
will be collected at the site for analysis of the urinary calcium excretion. Subjects will have their 
HPA axis function assessed and a baseline PK sample is collected along with other baseline 
assessments to confirm the subject’s eligibility before Day 0/Visit 1. 
Subjects who fulfil all inclusion and exclusion criteria at Day 0/Visit 1 are enrolled in the trial 
and will apply one dose of trial medication topically once daily for 8 weeks.   
Please refer to Figure 4-1 for an overview of the trial design. 
Trial subjects will be enrolled at approximately 12 sites in Europe.  
At Week 4 and Week 8, the effect of once-daily use of MC2-01 cream on the HPA axis and the 
calcium metabolism will be evaluated. Other assessments (local skin reactions, AEs, laboratory 
tests, electrocardiogram (ECG), vital signs and physical examination) and efficacy assessments 
are also performed. At Week 4, the PK profile of calcipotriol (CAL), betamethasone dipropionate 
(BDP) and their main metabolites MC1080 and betamethasone 17-propionate, respectively, will 
be assessed. 
The maximum trial duration for each subject will be approximately 18 weeks and includes a 
screening period of up to 6 weeks (if washout of medication is required), a treatment period of 8 
weeks, and a follow-up period of up to 4 weeks. After Week 8 (Visit 5) a follow-up visit is required 
for all subjects. The end of trial is defined as last subject last visit. 
Figure 4-1  
Trial Design  
 
        
 
      Screening Period* 
      8 Weeks Treatment Period 
               Follow-up Period 
 
 
 
 
 
Baseline 
End of 
 
Days -42 to -8 
Visit SV1 
 Day -7 to -4 
Visit SV2 
  Day 0              Weeks 2, 4, 6 
 Visit 1               Visits 2, 3, 4 
Treatment 
Week 8 
Visit 5 
 
 
 
*There should be at least four days between SV1 and SV2 in order to keep the food diary for 4 days prior to SV2.  
 
 
 
MC2-01 cream 

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4.2 
Trial Endpoints 
Primary Endpoints 
HPA axis 
Subjects with serum cortisol level of less than 18 µg/dL at 30 minutes after ACTH challenge test 
at Week 4 and Week 8.  
 
Calcium metabolism 
Changes from Baseline to Week 4 and Week 8 in: 
• Albumin-corrected serum calcium; 
• Ratio of urinary calcium to creatinine*. 
*Spot analysis, second morning urine sample 
Secondary Endpoints  
Plasma PK parameters (AUC0-t, AUC0-5, Cmax and Tmax) will be calculated at Week 4. The PK 
parameters AUC0-5 and Cmax will be calculated using standard formulas inserting the lower limit 
of quantification (LLOQ) for non-quantifiable levels of the analyte; therefore, AUC0-5 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 and Tmax will be calculated if at least one time-point 
shows a quantifiable level of the analyte. The PK parameters will be summarised using appropriate 
descriptive statistics including median, lower and upper quartiles, minimum and maximum. 
Blood samples for PK assessments will be collected at 
• SV2 (baseline sample)   
• Week 2 (single time point before application of IP) 
• Week 4; before application of IP and then at 1, 3, and 5 hours after the application.  
• Week 8; (single time point. Subject should not apply IP on the day of the Week 8 visit) 
The samples will be assayed for concentrations of the active ingredients (BDP and CAL) and for 
their main metabolites; MC1080 and betamethasone 17-propionate, respectively.  
Safety Endpoints  
Safety endpoints include the following: 
• Adverse events (AEs) and serious adverse events (SAEs); 
• Local skin reaction; 

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• Changes in safety laboratory test results; 
• Changes in ECGs; 
• Changes in vital signs and physical examinations 
Other Endpoints 
• The proportion of subjects with treatment success, defined as a minimum 2-point decrease 
from baseline in the PGA on the body (trunk and/or limbs), and with or without scalp at Week 
4 and Week 8.  
• Subject assessment of treatment convenience at Week 8 using a Psoriasis Treatment 
Convenience Scale.   
5.0 
SELECTION OF TRIAL POPULATION 
5.1 
Subject Population 
It is planned to enroll approximately 30 subjects. The choice of sample size in this trial is based 
on regulatory considerations with respect to common practice in maximum use studies. For the PK 
population, the aim is to have at least 20 subjects included that have at least completed Week 4 
(Visit 3). 
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. 
A written informed assent will be signed and dated by the subject and an informed consent 
document (ICF) will be signed and dated by the parent(s) or legal guardian(s) 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. 
The parent(s), or legal guardian(s) (according to national law) have provided written 
informed consent following their receipt of verbal and written information about the trial; 
2. 
The subject (according to national law) has provided written assent to the trial following 
their receipt of verbal and written information about the trial; 
3. 
Generally healthy males or non-pregnant females, of any race or ethnicity, who are between 
12 to 16 years, 11-month-old at SV1;   
4. 
At Visit 1/Day 0, have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 
6 months duration involving body (trunk and/or limbs), with or without scalp;  

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5. 
Have a treatment area between 10% and 30% of the BSA on the body (trunk and/or limbs) 
and scalp, excluding psoriatic lesions on the face, genitals, and intertrigenous areas, at Visit 
1/Day 0;  
6. 
Have a PGA of at least moderate severity on the treatment area;  
7. 
A normal HPA axis function including a serum cortisol concentration above 4.5mcg/dl 
(160nmol/l) before ACTH-challenge and equal or above 18 mcg/dl (500 nmol/l) 30 minutes 
after ACTH challenge, at SV2;  
8. 
A serum albumin-corrected calcium below the upper reference limit at SV2; 
9. 
Female subjects must have a negative urine pregnancy test result at SV1, and if sexually 
active they must agree to use a highly effective method of contraception (i.e. a method with 
a failure rate of less than 1% per year when used consistently and correctly) for two months 
prior to Visit 1 and until the follow-up visit has been performed. Highly effective 
contraception allowed in this trial is defined as follows:  
• intrauterine device (IUD) 
• bilateral tubal occlusion  
• vasectomised partner (provided that is the sole sexual partner of the subject and that 
the vasectomised partner has received medical assessment of the surgical success.) 
• sexual abstinence (if in line with the preferred and usual lifestyle of the subject and 
defined as refraining from heterosexual intercourse during the entire period of the 
trial. Periodic methods of abstinence (e.g. calendar, ovulation, sympto-thermal, post-
ovulation methods) are not accepted methods of contraception.) 
5.3 
Exclusion Criteria 
Subjects who fulfil any of the following criteria will be ineligible to participate in the trial: 
1. 
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 infections in the treatment area (e.g. skin infection with bacteria (including 
tuberculosis), viruses, parasites or fungi) or skin manifestations of atrophic skin, atrophic 
striae, skin vein fragility, ichthyosis, acne vulgaris, acne rosacea, rosacea, ulcers and 
wounds in the treatment area. 
4. 
Presence of pigmentation, extensive scarring, pigmented lesions or sunburn in the 
treatment areas, which could interfere with the rating of efficacy parameters;  
5. 
Planned excessive or prolonged exposure to either natural or artificial sunlight, including 
tanning booths, sun lamps, etc;  

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6. 
Use of phototherapy (psoralen + ultraviolet A radiation [PUVA] and ultraviolet B 
radiation [UVB]) within 4 weeks prior to SV2 and during the trial; 
7. 
Current or past history of disorders of calcium metabolism associated with 
hypercalcemia, vitamin D toxicity, severe renal insufficiency, or severe hepatic disorders; 
8. 
Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within 
4 weeks prior to SV2.  
Note: Stable doses of oral vitamin D supplementation ≤400 IU/day is permitted provided 
there are no dose adjustments during the trial period; 
9. 
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; 
10. Use or planned initiation of estrogen and/or progestogen therapy (e.g. hormonal 
contraception) during the trial; 
11. Strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors or inducers (e.g., 
clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, 
darunavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir, rifampicin, 
phenobarbital, phenytoin) within 4 weeks prior to SV2 and during the trial period; 
12. Use of topical treatments (eg, corticosteroids, vitamin D analogs, retinoids, PDE4 
inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar), except for emollients 
and non-medicated shampoos, with a possible effect on psoriasis within 2 weeks prior to 
SV2 and during the trial period;  
13. Systemic treatment with biological therapies, whether marketed or not, with a possible 
effect on psoriasis vulgaris within the following time period prior to SV2 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) 
In general, subjects who are candidates for biological or other systemic therapy are 
excluded from the trial. 
14. 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; 
15. Any of the following conditions, whether known or suspected: 

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• Clinically diagnosed depression where the subject is in current treatment with 
medication approved for treatment of depression 
• Endocrine disorders (e.g. Cushing’s disease or Addison’s disease) known to affect 
cortisol levels or HPA axis integrity.  
• Non-nocturnal sleep patterns (e.g. irregular sleep patterns) 
16. 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 SV2 and during the trial period; 
17. Use of live vaccines 4 weeks before SV2 and during the trial period;   
18. Known human immunodeficiency virus (HIV) infection, active hepatitis B or hepatitis C; 
19. Known or suspected of hypersensitivity to any component of the test product; 
20. Known allergic asthma, serious allergies or allergies where recurrent acute or chronic 
treatment is necessary (excluding hay fever); 
21. Have any chronic or acute medical condition that, in the opinion of the investigator, may 
pose a risk to the safety of the subject, or may interfere with the assessment of safety or 
efficacy in this trial;  
22. 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 IP or will interfere with the 
interpretation of the trial results; 
23. Females who are pregnant, breast feeding, or planning a pregnancy; 
24. Subject with known abnormal reduction in muscle mass, as judged by the investigator; 
25. Participation in another clinical trial or received an IP or non-marketed drug substance 
within 30 days prior to SV2; 
26. Previously enrolled in this trial; 
27. 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 Harmonisation (ICH) – 
Good Clinical Practice (GCP) guidelines, every subject has the right to refuse further participation 
in this trial at any time and without providing reasons (see also Section 9.2). A subject's 
participation is to be terminated immediately upon his/her request. The investigator should seek to 
obtain the reason and record this on the electronic case report form (eCRF) whenever possible. If, 

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at the time of refusal, a trial product has already been administered, the subject should also be 
advised to have an Early Termination visit performed (see section 7.13 Early Termination) and 
follow up on treatment related AEs. 
In 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. 
Examples of SAEs that do not necessarily require discontinuation of treatment include but are not 
limited to a hospitalisation that is not related to the IP, for example removal of tonsils or polyps.  
The reasons for discontinuation of treatment may be among others;  
• HPA axis suppression is noted at Week 4 
• inconsistency with inclusion / exclusion criteria 
• intake of a prohibited medication(s)  
• AE / SAE 
• investigator’s discretion 
Subjects discontinued treatment due to a treatment-related AE will be monitored until the AE is 
resolved or until the medical condition of the subject is stable. 
In case the treatment is discontinued all efforts should be made to have the subject completing the 
trial, or at least come in for the Week 8 visit, even if not being on treatment anymore.  
Reasons for discontinuation of the trial may be among others;  
• lost to follow-up,  
• withdrawal of informed consent / informed assent  
• pregnancy  
• investigator’s discretion 
• sponsor’s decision to terminate or suspend the trial  
• termination of the trial by the Regulatory Authority. 
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 approximately 20 subjects are included in the 
PK population at Week 4. 

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6.0 
TRIAL TREATMENTS 
6.1 
Investigational Product  
MC2-01 cream is a combination product, calcipotriol and betamethasone dipropionate, 
administered as a cream formulation for topical administration. The MC2-01 cream is currently 
not a marketed product, which means that the product is still being tested and is not approved for 
sale. One concentration of the trial product will be studied: calcipotriol (50 micrograms) and 
betamethasone (0.64 mg/g, as dipropionate). The list of inactive ingredients present in MC2-01 
cream is presented in the Investigator Brochure (37). 
6.2 
Dosing Regimen 
Subjects are to apply the IP topically once daily, preferably in the evening, for 8 weeks. The 
subject should apply enough IP to treat the entire affected areas and rub in gently to ensure that 
the plaques are saturated with the medication. Up to 3 tubes of 60 gram will be dispensed for a 
treatment period of two weeks including the allowed visit window of 2 days.  
 
The IP is applied to affected areas on the:  
• scalp  
• trunk (including the neck)  
• limbs  
o arms (including the back of the hands)  
o legs (including the buttocks and the top of the feet).  
 
Only affected areas are to be treated. The subjects should therefore not continue treatment on a 
skin area which has been cleared but treatment may be restarted in case of recurrence at the subjects 
discretion (Section 6.3). 
The face, genitals, and intertriginous areas should not be treated with the IP. The first application 
is done at Day 0 under the supervision and instruction of the trial staff. Subsequent applications 
will be applied by the subject or by the parent(s) or legal guardian(s). 
All subjects are instructed to apply IP in the morning on the day before the Week 2, Week 4 and 
Week 8 visits. On the day of these visits, the subjects should not apply any IP before the visit.  
Subjects are to record the date and time of application in the subject dosing diary (with the 
assistance of the parent(s) or legal guardian(s), as needed). The treated area should not exceed 30% 
of the BSA.  

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In case an AE reported in one area of the body lead the investigator to the decision to discontinue 
treatment this will apply for treatment in general and not only to the area for which the AE was 
reported. 
Detailed application instructions will be provided in the subject instructions.  
6.3 
Dose Modification 
Dose modification can only occur after Week 4. 
Subjects classified as clear at any of the on-treatment visits may stop the IP treatment at the 
investigator’s discretion. They should remain in the trial and attend all visits up to and including 
the follow-up visit. The IP will continue to be dispensed to the subject, and IP 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 IP treatment on the advice of the investigator 
at a scheduled visit. 
6.4 
Packaging, Labeling, Storage and Destruction 
Medication labels for the IP will comply with the legal requirements of the country where the trial 
is performed and be printed in the local language.  
The IP will be supplied by MC2s 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 pharmacy/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.  
All medication – unused and used - will be returned for reconciliation and destruction.   
6.5 
Assignment to Treatment 
This is an open-label trial.  All subjects who fulfil the trial eligibility requirements will be assigned 
to treatment with MC2-01. Hence, neither randomisation nor blinding will be performed. 
6.6 
Prior, Concomitant, and Prohibited Therapy 
All medications, including over-the-counter (OTC) drugs and vitamins, herbal and dietary 
supplements, taken within 30 days prior to the start of the trial will be recorded at Screening. 
Thereafter, a record of all medications and supportive therapy taken during the course of the trial 
will be made. Information regarding the total daily dose, route of administration, start and 
discontinuation dates, and indication are to be recorded on the subject’s eCRF. 

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6.6.1 
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). 
6.6.2 
Prohibited medications during the trial 
Use of any medication that would exclude the subject from participation in the trial (as specified 
in Section 5.3 Exclusion Criteria) is also prohibited during the treatment and follow-up periods, 
which includes medications in the following categories:  
• 
Use of biological psoriasis therapies;  
• 
Use of oral systemic treatments with a possible effect on psoriasis (e.g., methotrexate, 
apremilast, retinoids, PDE4 inhibitors, corticosteroids, and other immunosuppressants). 
• 
Use of phototherapy (PUVA and UVB). 
• 
Use of topical treatments with a possible effect on psoriasis (e.g., corticosteroids, vitamin 
D analogs, retinoids, PDE4 inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, 
tar, 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 or initiation of estrogen and/or progestogen therapy (e.g. hormonal contraception).  
• 
Use of strong systemic 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. 
6.6.3 
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. 
6.7 
Treatment Compliance 
Records of trial product used, and dosages administered will be kept during the trial. The trial 
monitor will note product accountability during site visits and at the completion of the trial. 
At all on-treatment visits, the subject will be asked if he/she has used the medication as prescribed. 
If this is not the case, the degree and nature of noncompliance will be specified. In addition, 
subjects will be asked to complete a dosing diary during the treatment period (with assistance from 
the parent(s) or legal guardian(s), if needed) as a measure of treatment compliance. Subjects who 
are consistently noncompliant will be counseled. 

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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 will be weighed to determine the amount of the IP used 
per treatment phase.  
7.0 
VISIT SCHEDULE AND ASSESSMENTS 
Table 7-1 
Visit Schedule and Assessments 
 
 
 

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SV 1 a 
SV 2 
Visit  
1 
Visit  
2 
Visit  
3 
Visit  
4 
Visit 
 5  
Follow-
up 
 Visit b  
 
 
 
Day 0 
Week 
2 
Week 
4 
Week 
6 
Week 
8 
FU 
Examination 
Day  
 - 42 
to 
Day -
8 
Day 
-7 to  
- 4 
Day 0  
Day 
14 ± 2 
Day 
28 ± 2 
Day 
42 ± 2 
Day 
56 ± 2 
Day 70- 
84 ± 2   
Informed assent/Informed 
consent c 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
(X) 
 
X 
 
 
 
 
 
Urine pregnancy testd 
X 
 
X 
 
 
 
 
 
Serum pregnancy testd 
 
X 
 
 
X 
 
X 
 
Demographics, medical 
history 
X 
 
 
 
 
 
 
 
Prior and concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
 
Physical examination 
X 
 
X  
 
X 
 
X 
X 
PGA  
(X) 
(X) 
X 
X 
X 
X 
X 
 
Body Surface Area (BSA) 
involvement 
(X) 
(X) 
X 
 
X 
 
X 
 
Vital signs 
 
 
X 
X 
X 
X 
X 
 
Laboratory assessments 
 
X 
 
 
X 
(X)e 
X 
(X) 
ACTH challenge testf 
 
X 
 
 
X 
 
X 
(X) 
Morning urine assessment 
(second morning urine) 
Instruct 
X 
 
Instruct 
Instruct 
X 
Instruct 
(X)g 
Instruct 
X 
(X) 
Review food diary  
Instruct 
X 
 
Instruct 
Instruct 
X 
Instruct 
(X)g 
Instruct 
X 
(X) 
PK pre-dose blood sample 
(Single) 
 
X 
Instruct 
X 
 
Instruct 
X 
 
PK serial blood samplesh 
 
 
 
Instruct 
X 
 
 
 
12-Lead ECG 
 
X 
 
 
X 
 
X 
 
Psoriasis Treatment 
Convenience Scale 
 
 
 
X 
X 
 
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)i 
 
X 
X 
X 
X 
X 
X 
X 
Local Skin Reactions 
 
 
X 
X 
X 
X 
X 
 

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a) A washout period of up to 6 weeks must be completed if the subject has been treated with 
anti-psoriatic treatments or other relevant medication, as defined by exclusion criteria.  
There should be at least four days between SV1 and SV2 in order to keep the food diary 
for 4 days prior to SV2. 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) Follow-up visit is required 2 weeks after the Week 8 visit. For subject with HPA axis 
suppression at Week 8 the follow-up visit should be 4 weeks after the Week 8 visit.  
If the albumin-corrected serum calcium or the urinary calcium creatinine ratio is elevated 
at Week 8 a repeat test should be performed. In case of a repeat of the urinary calcium 
creatinine ratio the subject should be instructed to record the calcium intake 4 days prior 
to the visit. 
For Czech Republic and Hungary: if an on-site visit is not required the follow-up visit 
can be a telephone call 2 weeks after Week 8 to ask for the wellbeing of the subject. In 
Germany an on-site follow-up visit is mandatory.    
In addition, subjects discontinued due to a treatment-related AE will be monitored until 
the AE is resolved or until the medical condition of the subject is stable.  
c) Written informed assent must be provided by the subject and written informed consent 
must be provided by the parent(s), legal guardian(s) and the consent documents signed by 
the investigator or designee before any trial related procedures are carried out. For 
subjects requiring a washout period, informed assent/informed consent must be 
completed prior to washout. 
d) All female subjects.  
e) If serum albumin-corrected serum calcium is above the reference range at Week 4 a 
repeat test should be performed at Week 6. 
f) The ACTH challenge test must be performed between 7 and 9 am   
g) If the urinary calcium:creatinine ratio is above the reference range at Week 4, a repeat 
test should be performed, and the food diary filled in at Week 6. If the repeat test is also 
above the reference range, 24-hour urine collection must be performed.   
h) Blood samples for PK analysis are drawn before IP application (pre-dose sample) and 1, 
3, and 5 hours after IP application. 
i) AEs are to be collected from the date of signing informed assent/informed consent and 
first trial-related activity is performed. 

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Instruct: At the indicated visits (Table 7-1), instruct the parent(s), legal guardian(s) or the 
subjects as to appropriate trial procedures as specified below: 
• Food diary: instruct the parent(s), legal guardian(s) or subjects on how to use the food 
diary, especially recording their intake of calcium-rich nutrients. Consumption of 
calcium-rich foods should be kept constant during 4 days prior to each morning urine 
collection. 
• Second morning urine samples: Second morning urine samples must be collected at the 
site on specific visits as specified in the visit schedule (Table 7-1).  
Food diary and morning urine sampling before Week 6 and Follow-up Visit is only 
relevant if urinary calcium:creatinine ratio is above the reference range at previous visit. 
Inform by telephone call a few days before the scheduled visit whether applicable or not. 
• IP application and PK blood samples: instruct the parent(s), legal guardian(s) or 
subjects to apply the IP in the morning on the day before the Week 2, Week 4 and Week 
8 visits. On the day of these visits, the subjects should not apply any IP before the visit. A 
reminder to the parent(s), legal guardian(s) or subjects may be needed a few days before 
the scheduled visit. If the subject has applied the IP in the morning prior to the visit, the 
visit must be rescheduled.  
 

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7.1 
Demographics and Medical History 
The following demographic and medical history must be collected:  
• Year of birth 
• Sex 
• Race 
• Ethic origin 
• Complete skin disease history  
• The year diagnosed with psoriasis vulgaris. If diagnosis is within the ongoing or preceding 
year, also month should be collected 
• All other current and past medical/surgical conditions within the last 12 months. 
The Fitzpatrick skin type will be assessed according to the classification scheme in Table 7-2. 
Table 7-2 
Fitzpatrick Skin Type Classification 
I 
Pale white skin, blue/hazel eyes, blond/red 
hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
  
7.2 
Prior and Concomitant Medication 
Review and record prior medication and concomitant medication. 
All medications, including OTC drugs, herbals, vitamins, dietary supplements etc., taken within 
30 days prior to the start of the trial will be recorded at Screening (SV1 and/or SV2). Thereafter, 
a record of all medications and supportive therapy taken during the trial will be made. Information 
regarding the total daily dose, route of administration, start and discontinuation dates, and 
indication are to be recorded on the subject’s eCRF. 
7.3 
Physical Examination 
An abbreviated physical examination including general appearance, regional lymph nodes and a 
complete dermatological examination of the skin must be performed, including height and 

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weight. without shoes, as specified in the visit schedule  
(Table 7-1).  
7.4 
Vital Signs 
Blood pressure and pulse rate will be taken with the subject in the sitting position with 
approximately 5 minutes’ rest prior to measurement. Body temperature (oral or ear) will be also 
be measured.  
7.5 
Pregnancy Test 
All female subjects will undergo a routine urine pregnancy test at SV1 and V1 (Day 0) and a serum 
pregnancy test at SV2, Week 4 & Week 8 as specified in the visit schedule (Table 7-1). Instruct 
all sexually active female subjects to use approved form(s) of contraception.  
7.6 
Laboratory Assessments 
All clinical laboratory specimens will be analysed by a central licensed and accredited laboratory 
facility according to the laboratory’s standard operating procedures (SOPs).  
7.6.1 
Hematology and biochemistry  
The planned maximum amount of blood drawn at each visit and for each subject is: 
Visit 
Maximum amount of blood drawn 
Screening Visit 2 (SV2) 
17 ml 
Week 2 
8 ml 
Week 4 
41 ml 
Week 6 
4 ml 
(only if albumin-corrected serum calcium is above the reference 
range at Week 4 and repeat test is required) 
Week 8 
17 ml 
Follow-up Visit 
9 ml 
(blood draw at the follow-up visit is only required if albumin-
corrected serum calcium is above the reference range or HPA axis 
suppression is noted at Week 8) 
 
To avoid too many venipunctures and thereby to cause as little pain, discomfort, fear and any other 
foreseeable risk as possible, it is recommended to use butterfly needles. This applies especially at 
the Week 4 visit where blood draw for the PK analysis will be repeated 4 times. In the event that 
butterfly needles cannot be used, it is important to minimize the number of attempts and it should 

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be assessed individually in each situation and should always be in agreement with the individual 
subject. 
The following tests will be performed as specified in Table 7-1: 
• 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, only at SV2 
Week 4: If albumin-corrected serum calcium is above the reference range at Week 4, a repeat test 
should be performed at Week 6.  
Week 8: If the albumin-corrected serum calcium is above the reference range at Week 8, a repeat 
test is required 14 days (± 2 days) after at a follow-up visit (see Section 7.12).  
7.6.2 
HPA axis suppression/ ACTH challenge test 
Adrenal function will be assessed in a challenge test with an intravenous dose of 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 SV2, Week 4 and Week 8 visits. The test consists of blood 
sampling starting between 7 and 9 am. 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 stimulation of the adrenal glands induced by 
cosyntropin.  
The following criterion will define an adrenal suppression:  
•  the 30-minute post-stimulation level below18 µg/dL (500 nmol/l). 
Week 4: If HPA axis suppression is noted at Week 4, 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 ACTH challenge test 
has to be repeated at a follow-up visit 28 days (± 2 days) after the Week 8 visit (see Section 7.12).   
7.6.3 
Food diary: calcium-rich nutrients   
All subjects should record their consumption of calcium-rich nutrients (mainly milk, other dairy 
products, calcium-fortified products) four days before each second morning urine collection (see  
Table 7-1). 

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Based on the diary entries, the number of daily calcium servings should be calculated for each day 
and recorded in the eCRF.  
7.6.4 
Analysis of Morning Urine Spot Samples 
All subjects are to collect second morning urine spot samples at the visits indicated in Table 7-1.  
The following urine analyses will be performed: 
• Calcium, phosphate, creatinine, volume, total calcium excretion, total phosphate excretion, 
total creatinine excretion, urinary calcium:creatinine ratio, urinary phosphate:creatinine 
ratio. 
The following provisions will apply for subjects with hypercalciuria, defined as a morning urinary 
calcium:creatinine ratio above the reference range (as defined in the laboratory manual):  
Week 4: If the morning urinary calcium:creatinine ratio is above the reference range at Week 4, a 
repeat test should be performed at Week 6.  
Week 8: If the urinary calcium:creatinine ratio is above the reference range at Week 8, a repeat 
test is required at a follow-up visit 14 days (± 2 days) after Week 8 (see 7.12).  
If the calcium-creatinine ratio is above the reference range at two consecutive visits during the 
trial, 24-hour urine collection must be performed.  
7.6.5 
Pharmacokinetics  
Samples for PK analysis will be collected though an untreated area of the skin, at the following 
time points: 
• SV2: single time point  
• Week 2 visit: single time point before IP application  
• Week 4 visit: before the planned IP application at the visit and then at 1, 3, and 5 hours after 
the application 
• Week 8 visit: single time point. Subject should not apply IP on the day of the Week 8 visit 
Subjects are to be instructed to apply their daily dose of IP in the morning on the day before the 
Week 2, Week 4 and Week 8 visits. On the day of these visits, the subjects should not apply any 
IP before 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) 

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7.7 
Electrocardiogram 
A 12-lead ECG will be recorded at visits indicated in Table 7-1. 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 judgement of the 
investigator.  
Clinically significant findings will be reported as medical history if detected at SV2. 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. 
7.8 
The Psoriasis Treatment Convenience Scale 
The Psoriasis Treatment Convenience Scale must be completed by the subjects before any other 
assessments are performed. The assessments are to be performed as specified in the visit schedule 
(see Table 7-1).  
The aim of the Psoriasis Treatment Convenience Scale is to assess the impact and convenience of 
psoriasis treatment. The scale has been tested for content validity through focus group interview 
with 20 patients and adapted based on the responses. The scale consists of 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 greasy did your skin feel after applying the treatment? 
5. How much did treating your skin disrupt your daily routine? 
6. Overall, how satisfied were you with the medical treatment? 
 
7.9 
Investigator Assessments 
The investigator assessments are to be performed by a dermatologist, a physician or a pediatrician 
with at least 1 year of experience in dermatology. For physicians and pediatricians who do not 
fulfill the requirement regarding dermatological experience with at least 1 year of experience in 
dermatology, the person must be preapproved by MC2. The assessments are to be performed as 
specified in the visit schedule (see Table 7-1). 
7.9.1 
Physician’s global assessment of psoriasis severity 
The 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 7-3. The PGA assessment will represent the average lesion severity on the trunk, limbs, 
and/or scalp. 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 7-3 
Physician’s Global Assessment (PGA) 
Score 
Grade 
Definition 
0 
Clear 
Plaque thickening = no elevation or thickening of normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red colouration but post-inflammatory 
hypo or hyperpigmentation may be present) 
1 
Almost 
clear 
Plaque thickening = none or possible thickening but difficult to ascertain 
whether there is a slight elevation above normal skin level 
Scaling = none or residual surface dryness and scaling 
Erythema = light pink colouration 
2 
Mild 
Plaque thickening = slight but definite elevation 
Scaling = fine thin scales partially or mostly covering lesions 
Erythema = light red colouration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = coarse scale layer at least partially covering most lesions 
Erythema = definite red colouration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with hard or 
sharp edges 
Scaling = non-tenacious or thick tenacious scale predominates, covering most 
or all of the lesions 
Erythema = very bright red colouration, extreme red coloration, or deep red 
colouration 
 
7.9.2 
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) as specified in the visit 
schedule (see Table 7-1). 
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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7.9.3 
Local skin reactions 
The local skin reaction assessment involves signs assessed by the investigator or designee and 
symptoms 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 7-4. 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 7-4 and the subject will tell which one to mark.  

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Table 7-4 
Local Skin Reaction Scores 
Investigator assessment of the lesional area 
 
0 (absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erosion/ulceration 
in lesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
Vesicles 
in lesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Investigator assessment of the perilesional area 
 
0=absent 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erythema  
in perilesional area 
None 
Barely visible 
erythema 
Distinct erythema 
Dark red erythema 
Scaling 
in the perilesional area 
None 
Barely visible 
scaling 
Distinct scaling 
Gross scales 
Edema 
in perilesional area 
None 
 barely palpable 
swelling 
Easily palpable 
swelling 
Gross swelling 
Atrophy 
in perilesional area 
None 
Barely visible 
thinning 
Distinct thinning 
Striae 
Vesicles  
in perilesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Erosion/ulceration 
in perilesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
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  
 
 
 

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7.10 
Adverse Events 
7.10.1 
Adverse events assessments 
The investigator or designee is responsible for obtaining, assessing, and documenting all AEs 
during the trial. AE information will be collected from the time of the signature of the informed 
assent/informed consent form and first trial-related activity performed until the end of the trial. An 
AE is an untoward medical occurrence in any subject during the trial which does not necessarily 
have a causal relationship with the IP.  
All AEs will be documented in the eCRF, including a description of each AE, AE relationship to 
IP administration, start and stop dates, seriousness, severity, action taken and outcome.  
Any AE that meets the serious criteria must be reported on the eCRF and on a separate SAEs report 
form. SAEs must be reported immediately to MC2 or designee as soon as it becomes known to the 
investigator and not later than within 24 hours of his/her knowledge of the occurrence of an SAE.  
Throughout the trial, the occurrence of AEs should be sought by nondirective questioning of the 
subject at each visit during the trial. Information on AEs can also be obtained from signs and 
symptoms detected during examination, observations made by the trial site personnel, or 
spontaneous reports from subjects. Pre-existing conditions that worsen during the trial should also 
be recorded as AEs. This will also include worsening of the psoriasis vulgaris as judged by the 
Investigator. 
AEs requiring therapy must be treated with recognised standards of medical care to protect the 
health and well-being of the subject. Treatment due to an AE will be recorded in the subject’s 
records and on the appropriate eCRF. 
Any AE that is considered related to the IP must be followed by the investigator until it is resolved 
or until the medical condition of the subject is stable; all relevant follow-up information will be 
reported to the MC2 or designee. 
The outcome of an AE will be classified as recovered, recovered with sequelae, 
recovering/resolving, ongoing, or death. 
7.10.2 
Timing 
AEs will be collected/assessed from the time of the signature of the informed assent/informed 
consent form by the subject/parent(s) or legal guardian(s) and first trial-related activity performed.  
7.10.3 
Severity of adverse events 
The investigator is to classify the severity (intensity) of an AE according to the following 
definitions: 
• Mild – The subject was aware of the signs and symptoms, but the signs and symptoms were 
easily tolerated and does not interfere with daily activity. 

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• Moderate – The signs and symptoms were sufficient to restrict, but did not prevent, usual 
daily activity for the subject. The subject is still able to function.  
• Severe – The subject was unable to perform usual daily activity. 
The maximum intensity of an AE (mild, moderate, or severe) will be assessed taking into 
account the possible range of intensity of the symptom(s). 
7.10.4 
Relationship of an adverse event to trial treatment 
The investigator is responsible for assessing 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 IP 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 IP are temporally related, and the AE is more likely 
explained by IP administration than by other causes 
Definitely Related 
The AE and IP administration are related in time, and a direct 
association can be demonstrated. Concomitant medication, therapeutics 
interventions, or underlying conditions do not provide a sufficient 
explanation for the observed AE 
7.10.5 
Unexpected adverse events 
Any AE assessed 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 (37). 
 “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 IP but are not specifically mentioned as occurring with 
the particular IP under investigation. 

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7.10.6 
IP overdose 
An overdose of the IP, i.e., a dose that is higher than the highest dose under clinical investigation 
or the known therapeutic dose, will be fully documented even if no toxic effects were observed 
and will be considered an AE. 
The application should only be done once daily, and the treated area should not be >30% of the 
body surface area.  
Use of MC2-01 cream in excessive amounts may cause elevated serum calcium, which should 
rapidly subside when treatment is discontinued. Excessive prolonged use of topical corticosteroids 
may suppress the pituitary-adrenal functions, resulting in secondary adrenal insufficiency that is 
usually reversible. In such cases, symptomatic treatment is indicated. 
7.10.7 
Pregnancy 
Any pregnancy occurring from date of the informed assent/informed consent signature until trial 
completion must be reported immediately to MC2 or designee as soon as it becomes known to the 
investigator and not later than within 24 hours of his/her knowledge of the occurrence of the 
pregnancy (see Section 13.2).  
Investigator must actively follow-up, document and report to MC2 or designee the progress of the 
pregnancy until outcome is reached.  
7.10.8 
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 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.  
If the investigator becomes aware of an SAE after the end of the clinical trial that is possibly related 
to the IP, he/she must inform the sponsor immediately. 
A suspected unexpected serious adverse reaction (SUSAR) is an SAE that is both unexpected (not 
consistent with the current Investigator’s Brochure (37), and for which there is evidence to suggest 
a causal relationship between the IP 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. 
7.11 
Unscheduled Visit 
An unscheduled visit may be performed at any time during the trial if judged necessary by the 
Investigator, such as for a severe reaction, a suspected pregnancy, clinically significant AE, or 
clinically significant local skin reaction result. Details of the event are to be recorded in the 
subject’s records. 
7.12 
Follow-up Visit/ Follow-up Telephone Call 
A follow-up visit is required for all subjects to ensure capturing of safety signals 2 weeks after 
Week 8, except for subjects where HPA axis suppression is noted at Week 8.  
In case HPA axis suppression at Week 8 has been noted, the follow-up visit including an ACTH 
challenge test should be performed 28 days (± 2 days) after Week 8.  
Physical examination and AE Assessment will be mandatory for all subjects. Other assessments 
will be performed depending on the results received at Week 8.  
Additional laboratory assessments will be performed for the following reasons: 
• 
If the albumin-corrected serum calcium was above the normal reference range at the Week 8 
visit a repeat test should be done 14 days (± 2 days) after.  
• 
If the urinary calcium:creatinine ratio is above the reference range at Week 8, a repeat test 
should be done 14 days (± 2 days) after.  

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For Czech Republic and Hungary: if an on-site visit is not required the follow up visit can be a 
telephone call 2 weeks after Week 8 to ask for the wellbeing of the subject. In Germany an on-site 
follow-up visit is mandatory.    
Subjects discontinued due to a treatment-related AE will be monitored until the AE is resolved or 
until the medical condition of the subject is stable. 
7.13 
Early Termination 
If a subject withdraws from the trial 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. 
• 
Assess compliance 
• 
Review any concomitant medication used since the previous trial visit. 
• 
Record any AEs. 
• 
Physical examination and vital signs   
• 
Perform a serum pregnancy test for females  
• 
ECG  
• 
Haematology and biochemistry.  
• 
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. 

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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. 
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 visit and have had at least one blood draw for PK 
assessment at Week 4. 
• Safety population: all subjects who are enrolled in the trial and dispensed the trial 
medication at Visit 1/Day 0, excluding subjects who return all of the trial medication 
unused. 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 show normal HPA function at 
SV2.  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 enrolled 
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 enrolled 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). 

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Plasma PK parameters (AUC0-t, AUC0-5, Cmax, and Tmax) will be calculated at Week 4. The PK 
parameters AUC0-5 and Cmax will be calculated using standard formulas inserting the LLOQ for 
non-quantifiable levels of the analyte; therefore, AUC0-5 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 and Tmax will be calculated if at least one time-point shows a quantifiable level of the 
analyte. The PK parameters will be summarised using appropriate descriptive statistics including 
median, lower and upper quartiles, minimum and maximum. 
A parametric model will be applied to estimate the geometric mean of Cmax and AUC0-5, 
respectively. The log-transformed values of the PK parameters will be assumed to be normally 
distributed. The mean of this normal distribution will be estimated taking the potential censoring 
of the values into account.  The mean will then be back-transformed to the original scale as the 
geometric mean. 
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 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. Adverse events will be presented in 
data listings and summarised by frequency and severity.  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 proportion of subjects with HPA-axis suppression at Week 4 and Week 8 will be summarised 
using frequency counts.   
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 
– 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 AEs will be summarised by the overall incidence of at least one 
event, incidence by body system, and incidence by body system and preferred term.  Each subject 

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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 AE is treatment-emergent if its date of onset is Day 1 (Baseline) or later. 
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 summarised by presenting shift tables using extended normal 
ranges (baseline to most extreme post-baseline value), by presenting summary statistics of raw 
data and change from baseline values (means, medians, standard deviations (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. 
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 will be summarised. 
8.9.2 
Psoriasis treatment convenience scale 
Subject assessment of treatment convenience at Week 4 using a Psoriasis Treatment Convenience 
Scale will be summarized. 
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.  

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These requirements for approval should in no way prevent any immediate action from being taken 
by the investigator or MC2 in the interests of preserving the safety of all subjects included in the 
trial. If an immediate change to the protocol is felt to be necessary by the investigator and is 
implemented for safety reasons, MC2 or designee should be notified, and the IRB should be 
informed according to their reporting requirements. 
9.2 
Termination or Suspension of the Trial 
MC2, the IRB/IECs or competent authorities serve the right to terminate or suspend the trial, part 
of the trial or a trial site at any time. In case of premature termination or suspension of the trial, 
the contract research organisation (CRO) project manager will promptly inform the investigators, 
regulatory authorities, and IRBs about the premature termination or suspension, including the 
reason for it. In terminating the trial, MC2 and the investigator will ensure that adequate 
consideration is given to the protection of the subjects’ interests.  The trial must be terminated if 
the perception of the benefit/risk ratio (judged from clinical signs and symptoms, (S)AEs and/or 
remarkable safety laboratory changes) becomes unfavourable for the continuation of the trial.  
 
10.0 
DATA HANDLING AND RECORD KEEPING 
10.1 
Recording of Data 
10.1.1 
Source documents 
Source data are all the information in original records and copies of original records of clinical 
findings, observations, or other activities in the trial, which are necessary for the reconstruction 
and evaluation of the trial.  
Trial data collection procedures must ensure that each data element can be traced with a high level 
of confidence from its originator or recorder to its representation in the trial database and then to 
its place in the analysis and report of trial results. Once recorded, the trial data must be protected 
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. 

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

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well-being of the subjects have been adequately protected, and that all data relevant for the 
evaluation of the IP have been processed and reported in compliance with GCP/ICH and applicable 
regulatory requirements. 
The investigator is to notify 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 assent/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 has provided informed assent and each parent(s) or 
legal guardian(s) (according to national law) have provided written informed consent following 
their receipt of verbal and written information about the trial to participate in the trial. No trial-
specific procedures will be performed before a subject’s informed assent/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 assent/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 

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informed assent/informed consent. The Informed Consent document will include a request of the 
subject’s consent to release the collected data for research purposes in such a way that the 
individual’s identity remains masked. While all data records will be identified by the 
corresponding subject number, the identity of the subject will be held in confidential source 
documents at the trial site. All trial personnel with access to this information are legally bound not 
to disclose such information. 
13.0 
EMERGENCY PROCEDURES 
13.1 
Emergency Unblinding (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 immediately as 
it becomes known to the investigator (and not later than within 24 hours of his/her knowledge of 
the occurrence of an SAE) electronically to the UBC using the SAE Reporting Email address or 
fax number.  
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. 

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

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16.0 
REFERENCES 
 
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Arrabal-Polo MA, Arias-Santiago S, Giron-Prieto MS, Abad-Menor F, Lopez-Carmona Pintado 
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34. 
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Kragballe K, Austad J, Barnes L, Bibby A, de la Brassinne M, Cambazard F, et al. A 52-week 
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Mc2Therapeutics. Investigational brochure, version 4, 2018 or most current version. 
 
 

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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 Authors 
Marianne Thrane, Medical Writer, MC2 Therapeutics 
Johan Selmer, MD, VP Medical Affairs, MC2 Therapeutics  
Birgitte Vestbjerg, Director Clinical Operation, MC2 Therapeutics 
Charlotte Hindsberger, Principal consultant, Biostatistics, S-cubed 
 
 
 

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17.2 
Appendix 2  
Vendors  
Responsible for all services related to the conduct of the trial:  
Proinnovera GmbH; Contract Organization for Clinical Research and Development, 
Wienburgstraße 207; 48159 Münster, Germany. 
 
Responsible for all services related to central laboratory analysis:  
MLM Medical Labs GmbH, 41066 Moenchengladbach, Germany. 
 
Responsible for all services related to packaging, labeling, distribution and destruction of the 
investigational medical products:  
Rachel Hopkins BPharm (Hons), MRPharmS, PhD  
Director and Pharmacist, IMP Pharmaceutical Services Ltd.   
 
Responsible for providing electronic data capture services:  
Data MATRIX Ltd., 14a Nekrasova Street, Let.A, 4th Floor, Saint-Petersburg, 191014, Russian 
Federation. 
 
Responsible for ECG services:  
ERT, Peterborough Business Park, Lynch Wood, Peterborough, PE2 6FZ, UK. 
 
Responsible for services related to SAE reporting and tracking, as specified in the contract: 
United BioSource Corporation (UBC), Chemin des Coquelicots 16, CH-1214 Vernier Geneva, 
Switzerland.  
  
Responsible for PK analysis, as specified in the contract:  
ICON Laboratory Services Inc., 8282 Halsey Road, Whitesboro, NY 13492 USA.