Clinical trial NCT03819218
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics
Start date: 2018-12-27; Completion date: 2020-12-11
Enrollment: 7 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
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.

Detailed description:
The MC2-01 cream is designed for optimal patient satisfaction - it quickly absorbs into the skin leaving it nicely moisturized allowing patients to move on with daily routines. In this trial, subjects who fulfil all inclusion and exclusion criteria are enrolled in the trial and will apply one dose of trial medication topically once daily for 8 weeks. The purpose of the trial, is to determine the and pharmacokinetic parameters of MC2-01 cream in adolescent subjects under maximum use conditions.

Arms: arm 1: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) cream. One application daily for 8 weeks
Interventions: intervention 1: MC2-01 cream
Intervention descriptions: intervention 1: MC2-01 cream (Calcipotriene/betamethasone dipropionate, w/w 0.005%/ 0.064%)

Protocol documents:
Prot_000.pdf: 
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 
 
- 4 - 
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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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 
 


MC2 Therapeutics 
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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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. 
 


MC2 Therapeutics 
Clinical Trial Protocol 
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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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Clinical Trial Protocol 
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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 


MC2 Therapeutics 
Clinical Trial Protocol 
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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 


MC2 Therapeutics 
Clinical Trial Protocol 
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23 September 2018 
 
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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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Clinical Trial Protocol 
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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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Clinical Trial Protocol 
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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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Clinical Trial Protocol 
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23 September 2018 
 
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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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Fleming C, Ganslandt C, Guenther L, Johannesson A, Buckley C, Simon JC, et al. Calcipotriol 
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Calcium Measurements with Spot Urine. Eur J Gen Med. 2013;10(1):20. 
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Arrabal-Polo MA, Arias-Santiago S, Giron-Prieto MS, Abad-Menor F, Lopez-Carmona Pintado 
F, Zuluaga-Gomez A, et al. Hypercalciuria, hyperoxaluria, and hypocitraturia screening from 
random urine samples in patients with calcium lithiasis. Urol Res. 2012;40(5):511-5. 
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Strohmaier WL, Hoelz KJ, Bichler KH. Spot urine samples for the metabolic evaluation of 
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32. 
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O'Brien KO, Abrams SA, Stuff JE, Liang LK, Welch TR. Variables related to urinary calcium 
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34. 
Mack MC, Chu MR, Tierney NK, Ruvolo E, Jr., Stamatas GN, Kollias N, et al. Water-Holding 
and Transport Properties of Skin Stratum Corneum of Infants and Toddlers Are Different from 
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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.  
 
 
 
 
 
 
 
 
 
 
 
 

SAP_001.pdf: 
 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 1 out of 143 
 
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 
SAP version: 
SAP for Interim Analysis Final 3.0 dated 07 September 2020 
Effective date: 
07 September 2020 
 
 
Reviewed and 
Approved by 
Johan Selmer 
Chief Medical Officer, MC2 Therapeutics 
 
Date:_____________ 
Signature: _________________ 
Reviewed and 
Approved by 
Irene Sandholdt 
Senior Project Manager, MC2 Therapeutics 
 
Date:_____________ 
Signature: _________________ 
Reviewed and 
Approved by 
Cathrin Baum 
Project Manager, proinnovera GmbH 
 
Date:_____________ 
Signature: _________________ 
Reviewed and 
Approved by 
Leyla Tsakuginova 
Lead Clinical Data Manager 
 
Date:_____________ 
Signature: _________________ 
Reviewed and 
Approved by 
Georgiy Smirnov 
 
Head of Statistical Programming, 
Data MATRIX 
 
Date:_____________ 
Signature: _________________ 
Prepared by 
Kristina Bondareva 
Head of Biostatistics Department, 
Data MATRIX 
 
Date:_____________ 
Signature: _________________ 


 
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Revision History 
№ Date 
Changes Implemented 
Version Number 
1 
21JUL2020 
New document 
1.0 
2 
25AUG2020 
Updates for Finalization: 
List of laboratory parameters for analysis and 
corresponding units was corrected. 
Mistypes were corrected. 
2.0 
3 
07SEP2020 
Updates after Data Review Meeting: 
Listing of Study Drug Accountability was 
added.  
Numbering of TFLs was updated. 
Minor changes in the TFLs shells were 
implemented. 
In Section 10 it was specified that Cmax is 
determined as maximum of the observed 
concentration values after dosing. 
3.0 
 
 
 


 
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Table of Contents 
1. Abbreviations and Definitions ............................................................................................................................ 5 
2. Introduction ........................................................................................................................................................ 6 
3. Study Objectives and Endpoints ......................................................................................................................... 6 
3.1. Study Objectives .......................................................................................................................................... 6 
3.2. Endpoints ..................................................................................................................................................... 7 
4. Study Design ...................................................................................................................................................... 8 
4.1. General Study Design and Plan ................................................................................................................... 8 
4.2. Randomization and Blinding ..................................................................................................................... 11 
5. Sample Size ...................................................................................................................................................... 12 
6. General Considerations ..................................................................................................................................... 12 
6.1. Timing of Analyses.................................................................................................................................... 12 
6.2. Analysis Populations ................................................................................................................................. 12 
6.3. Missing Data .............................................................................................................................................. 13 
6.4. Interim Analyses and Data Monitoring ...................................................................................................... 14 
6.5. Multi-center Studies................................................................................................................................... 14 
6.6. Multiple Testing ........................................................................................................................................ 14 
7. Summary of Study Data.................................................................................................................................... 15 
7.1. Subject Disposition .................................................................................................................................... 16 
7.2. Protocol Deviations ................................................................................................................................... 17 
7.3. Demographic and Baseline Variables ........................................................................................................ 17 
7.4. Concurrent Illnesses and Medical Conditions ........................................................................................... 18 
7.5. Prior and Concurrent Medications ............................................................................................................. 19 
7.6. Prior and Concurrent Procedures ............................................................................................................... 20 
8. Efficacy Analyses ............................................................................................................................................. 20 
9. Safety Analyses ................................................................................................................................................ 20 
9.1. Exposure .................................................................................................................................................... 20 
9.2. Adverse Events .......................................................................................................................................... 21 
9.3. Pregnancies ................................................................................................................................................ 23 
9.4. Clinical Laboratory Evaluations ................................................................................................................ 23 
9.5. Other Safety Measures ............................................................................................................................... 24 
10. Pharmacokinetics ............................................................................................................................................ 28 
11. Other Analyses ............................................................................................................................................... 30 
12. Reporting Conventions ................................................................................................................................... 31 
13. Technical Details ............................................................................................................................................ 32 
14. Summary of Changes to the Protocol ............................................................................................................. 32 
15. References ...................................................................................................................................................... 32 
16. Listing of Tables, Listings and Figures .......................................................................................................... 33 
16.1. Tables ...................................................................................................................................................... 33 
16.2. Figures ..................................................................................................................................................... 34 
16.3. Listings .................................................................................................................................................... 35 
Appendix 1. TFLs Shells ...................................................................................................................................... 36 
Tables Shells ..................................................................................................................................................... 36 
Subject Disposition ........................................................................................................................................... 36 
Protocol Deviations .......................................................................................................................................... 40 
Demographic Characteristics ............................................................................................................................ 41 
Baseline Variables ............................................................................................................................................ 43 
Medical History ................................................................................................................................................ 47 
Prior and Concomitant therapy ......................................................................................................................... 49 
Exposure ........................................................................................................................................................... 51 
Pharmacokinetics Analyses .............................................................................................................................. 54 
Safety Analyses ................................................................................................................................................ 58 
Adverse Events ............................................................................................................................................. 58 
HPA Axis Suppression ................................................................................................................................. 66 
Calcium Metabolism ..................................................................................................................................... 70 
Clinical Laboratory Evaluation ..................................................................................................................... 72 
Local Skin Reactions Assessment ................................................................................................................ 78 


 
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Vital signs ..................................................................................................................................................... 83 
Physical Examination ................................................................................................................................... 88 
ECG .............................................................................................................................................................. 90 
Physician Global Assessment of Psoriasis Severity ..................................................................................... 96 
Body Surface Area Involvement Assessment ............................................................................................. 100 
Psoriasis Treatment Convenience Scale ..................................................................................................... 102 
Figures Shells ................................................................................................................................................. 104 
Listings Shells................................................................................................................................................. 106 


1. Abbreviations and Definitions 
The abbreviations and the definitions used in this document are listed below. 
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 
BLQ 
Below limit of quantification 
BSA 
Body surface area 
CAL 
Calcipotriene (United States term) / Calcipotriol 
(European Union term) 
Cmax 
Maximum plasma drug concentration 
CRO 
Contract Research Organisation 
CSR 
Clinical Study Report 
CYP 3A4 
Cytochrome P450 3A4  
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
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 
LSR 
Local Skin Reactions 
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 
PTCS 
Psoriasis Treatment Convenience Scale 
PTH 
Parathyroid hormone 
PUVA 
Psoralen + ultraviolet A 
RBC 
Red blood cell 
SAE 
Serious adverse event 
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 


 
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US  
United States 
UVB 
Ultraviolet B 
WBC 
White blood cell 
2. Introduction 
This SAP is written according to ICH E9 Guideline [1] and Data MATRIX LLC SOP [2, 3] using 
the Protocol Final version 5.0 dated 23SEP2018 including Amendment dated 09JUN2020 and CRF 
Final version 1.2 dated 09JUL2020. 
The purpose of this document is to provide a more technical and detailed elaboration of the 
principal features of the analysis, described in the Protocol, and to include detailed procedures for 
executing the statistical analysis. 
Based on FDA recommendation the trial is subject to a Temporary Halt, for non-safety reasons, 
to evaluate the study data in an interim analysis. It was decided to include data from all subjects 
who has been enrolled in the trial at the time of the interim analysis and perform analysis of all 
endpoints initially planned in the clinical study protocol.  
This SAP needs to be finalized and signed prior to database lock for interim analysis and 
applies to the interim data analysis. Revisions to the approved SAP may be made prior to database 
lock for the interim analysis. In case of deviation from the finalized SAP, explanation will be 
provided in the clinical study report (CSR). 
The interim report will be shared with FDA as post-approval supplement. Based on this report 
and subsequently feedback from FDA, it will be decided if the MC2-01-C6 study should be 
permanently closed or re-activated. In case the decision is made to resume the recruitment into the 
study, final statistical analysis will be conducted. A separate SAP will be prepared and finalized 
before the database lock for the final analysis. 
3. Study Objectives and Endpoints 
3.1. Study Objectives 
3.1.1. Primary Objective 
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. 
3.1.2. Secondary Objective 
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. 
 


 
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3.2. Endpoints 
3.2.1. Primary Endpoint 
• HPA axis 
Subjects with serum cortisol level of 18 µg/dL or less 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 
 
3.2.2. 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. 
 
3.2.3. Safety Endpoints 
• Adverse events (AEs) and serious adverse events (SAEs); 
• Local skin reaction; 
• Changes in safety laboratory test results; 
• Changes in ECGs; 
• Changes in vital signs and physical examinations. 
 
3.2.4. 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. 


 
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• Subject assessment of treatment convenience at Week 8 using a Psoriasis Treatment 
Convenience Scale. 
4. Study Design 
4.1. General Study Design and Plan1 
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 
 (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 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. 
 
Figure 1 
 
 
1 This section is based on the sections 4.1 “Overall Trial Design. 


 
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      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.  
 
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. 
 
Table 1 
Schedule of Activities 
MC2-01 cream 


 
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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 
 


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 intact 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 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, before IP 
application. 
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. 
 
4.2. Randomization and Blinding2 
This is an open-label trial. All subjects who fulfil the trial eligibility requirements will be 
assigned to treatment with MC2-01. Neither randomization nor blinding will be performed. 
 
2 This section is based on the section 6.5 “Assignment to Treatment” of clinical study Protocol. 


 
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5. Sample Size3 
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). 
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. 
6. General Considerations 
6.1. Timing of Analyses 
One interim analysis following study completion by 7 treated subjects will be prepared.  
 
The final analysis will be prepared in case the MC2-01-C6 is re-activated (refer to Section 6.4). 
6.2. Analysis Populations 
The main subject samples of interest are defined as follows. 
The ‘All enrolled subjects’: all subjects for whom Informed Consent/Assent were obtained: 
 
The ‘Allocated to treatment’: all subjects for whom Informed Consent/Assent were obtained and 
who had successfully completed Screening procedures and to whom any amount of trial 
medication was dispensed. 
 
The ‘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. 
 
The ‘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. 
 
The ‘HPA population’: all subjects in the Safety population that show normal HPA function at 
SV2:  
• 
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. 
 
The HPA population will be used for the HPA axis suppression analysis. 
 
 
3 This section is based on the section 5.1 “Subject Population” and 8.2 “Sample Size and Power Considerations” of 
clinical study Protocol. 


 
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For interim analyses Interim <Population Name> will be used for reporting.  
 
6.3. Missing Data 
No imputation will be made for missing data apart from missing or partial adverse event start 
date and concomitant medication end date necessary to calculate the treatment-emergent and 
prior/concomitant/post-treatment flags, correspondingly.  
 
If the information about end date for prior/concomitant therapy is missing or incomplete, the 
following rules (Table 2.1.1 and Table 2.1.2) will be used for the classification of therapy as prior, 
concomitant or post-treatment. 
 
Table 2.1.1  Management of partial and missing prior/concomitant therapy start date. 
Day 
Month 
Year 
Processing 
is missing 
is known 
is known 
Therapy will be classified as post-
treatment, if start month and year > 
month and year of the last IMP dose, 
else – as prior or concomitant according 
to the definition and Table 2.1.2 
is missing 
is missing 
is known 
Therapy will be classified as post-
treatment, if start year > year of the last 
IMP dose, else – as prior or 
concomitant according to the definition 
and Table 2.1.2 
is known 
is missing 
is known 
is missing 
is known 
is missing 
Therapy will be classified as prior or 
concomitant according to the definition 
and Table 2.1.2 
is known 
is missing 
is missing 
is missing 
is missing 
is missing 
 
 
Table 2.1.2  Management of partial and missing prior/concomitant therapy end date. 
Day 
Month 
Year 
Processing 
is missing 
is known 
is known 
Therapy will be classified as prior, if 
end month and year < month and year 
of the first IMP dose, else – as 
concomitant 
is missing 
is missing 
is known 
Therapy will be classified as prior, if 
end year < year of the first IMP dose, 
else – as concomitant 
is known 
is missing 
is known 
is missing 
is known 
is missing 
Therapy will be classified as 
concomitant 
is known 
is missing 
is missing 
is missing 
is missing 
is missing 
 
The medical history records will be categorized in prior/concurrent categories in a similar way. 


 
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If the information about adverse event start date and time is missing or incomplete, the 
following rules (Table 2.2) will be used for the classification of adverse events as TEAEs and non-
TEAEs (occurred before the start of study treatment) and for identification of TEAEs occurred up to 
Week 4. 
Table 2.2  Management of partial and missing AE start date. 
Day 
Month 
Year 
TEAE flag 
Occurrence up to Week 4 
is 
missing 
is 
known 
is 
known 
AE will be classified as 
TEAE, if month and year ≥ 
month and year of the first 
dose of study therapy  
TEAE will be classified as occurring 
up to Week 4, if month and year <= 
month and year of the Visit 3 / Week 
4 or subject discontinued before Visit 
3 / Week 4   
is 
missing 
is 
missing 
is 
known 
AE will be classified as 
TEAE, if year ≥ year of the 
first dose of study therapy  
TEAE will be classified as occurring 
up to Week 4, if year <= year of the 
Visit 3 / Week 4 or subject 
discontinued before Visit 3 / Week 4   
is known 
is 
missing 
is 
known 
is 
missing 
is 
known 
is 
missing 
AE will be classified as 
TEAE 
TEAE will be classified as occurring 
up to Week 4 
is known 
is 
missing 
is 
missing 
is 
missing 
is 
missing 
is 
missing 
 
Original dates (without imputation) will be used for data listings. 
 
6.4. Interim Analyses and Data Monitoring4 
Based on FDA recommendation the trial will be subject to a Temporary Halt to evaluate 
the study data in an interim analysis and create an interim report.  
The interim report will be shared with FDA as post-approval supplement. Based on this report and 
subsequently feedback from FDA, it will be decided if the MC2-01-C6 study should be 
permanently closed or re-activated.  
Interim analysis will be conducted on complete data from all subjects who had been 
enrolled into the trial at the time of interim analysis. Interim analysis will include the analysis of 
all endpoints initially planned in the clinical study protocol.  
  
6.5. Multi-center Studies 
Data from all centers will be merged and analyzed as one population for all study endpoints. 
6.6. Multiple Testing 
No adjustment for multiplicity is planned. 
 
4 This section is based on the section 8.11 “Interim analysis” of clinical study Protocol including Amendment. 


 
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7. Summary of Study Data 
Demographic and other baseline characteristics and safety data will be summarized by time 
point of assessment and listed.        
Default Summary Statistics 
The default summary statistics for quantitative and ordinal variables will be the number of 
observations (n), mean, standard deviation (SD), median, minimum (Min) and maximum (Max). 
Default Frequency Tabulations 
For qualitative variables, the number and percentage (n, %) of subjects with non-missing data per 
category and total number of subjects with non-missing data where applicable will be the default 
summary presentation. 
For AEs, medical history, concomitant medications and protocol deviations, however, the 
denominator for the percentage calculation will be the number of subjects in the corresponding 
population.  
The number of decimals for each descriptive statistic will be determined by the following rules: 
− mean, median: +1 decimal symbols compared to the analyzed variable values; 
− standard deviation: +1 decimal symbols compared to the analyzed variable values; 
− first (Q1) and third (Q3) quartiles: +1 decimal symbols compared to the analyzed variable 
values; 
− minimum and maximum values: the same as for the analyzed variable values; 
− percentages will be rounded to one decimal symbol; 
− confidence intervals will be presented with accuracy of the estimated value. 
The maximum number of decimal places in the statistical report is four. If some descriptive 
statistic has more than four decimal places after above mentioned rules application, this value will 
be rounded to four decimal places. 
Statistical Tests and Common Calculations 
Unless otherwise specified in the description of the analyses, the following arrangements will be 
applied: 
− 95% two-sided confidence intervals (CI); 
− CIs for mean values will be calculated based on normal distribution (SAS procedure 
UNIVARIATE with CIBASIC option); 
− CIs for proportions will be computed using the exact (Clopper-Pearson) method. 
For descriptive statistics, the following rules will be applied: 
− “<X.XX” results (e.g. below the limit of quantification, BLQ) for safety laboratory 
parameter values will be imputed with numeric result calculated as X.XX – 0.01. The 
number to be subtracted will be defined based on number of decimal places in observed 
values (e.g., if number of decimal places is 0 subtract 1, if number of decimal places is 1 
subtract 0.1, etc.). Imputed data will be used in summaries and calculations, but original 


 
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result will be listed. 
For quantitative measurements, changes from baseline will be calculated as [value at post-
baseline visit X – baseline value].  
The baseline value for a variable in common cases is defined as the last non-missing value 
collected before the first study drug application. 
Study day for each event will be calculated from the reference start date (date when subject was 
first exposed to study drug). 
If the date of the event is on or after the reference date, then 
study day = (date of event – reference date) + 1. 
If the date of the event is prior to the reference date, then 
study day = (date of event – reference date). 
For partial dates study day will not be calculated. 
 
The following visit windows were defined in the clinical study protocol: 
 
Visit Name 
Visit 
Short 
Name 
Anchor 
Target 
Day 
First day of 
the 
visit 
window  
Last day of 
the 
visit 
window 
Screening Visit 1 
SV1 
First application - 
-42 
-8 
Screening Visit 2 
SV2 
First application - 
-7 
-4 
Visit 1 (Day 0) 
V1 (Day 0) 
First application  1 
1 
1 
Visit 2 / Week 2 
V2/Week 2 
First application 15 
13 
17 
Visit 3 / Week 4 
V3/Week 4 
First application 29 
27 
31 
Visit 4 / Week 6 
V4/Week 6 
First application 43 
41 
45 
Visit 5 / Week 8 
V5/Week 8 
First application 57 
55 
59 
Follow-up Visit 
FU 
Last application 
15 
13 
17 
 
Assessments performed out of the planned visit windows will be assigned to the nearest of the 
surrounding planned visits if there is no valid result from a planned assessment for this visit. If 
assessments at both surrounding visits are missing and they are equidistant, the assignment is 
performed to the later one. Otherwise the assessments will not be included in summaries and 
will be listed only.  
 
Unscheduled and early termination visit assessment can be assigned to the planned visit in a 
similar manner. Unscheduled assessment can also be used in the derivations such as baseline or 
most extreme post-baseline assessments. All assessments including unscheduled should be 
presented by subject in the data listings. 
7.1. Subject Disposition 
The following disposition summaries will be provided: 
• A summary of the number of subjects who provided the informed consent / informed assent, 
the number of screen failures (including those subjects who satisfied the inclusion/exclusion 
criteria but for whom no study drug was dispensed) with reasons for premature study 
termination 
• A summary of the number of screen failure subjects violated any inclusion/exclusion criterion, 


 
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by criterion 
• A summary of the number of subjects allocated to treatment, the number and percentage of 
subjects attended each study visit (Allocated to treatment set) 
• A summary of the number and percentage of subjects included in each population for 
statistical analysis (Allocated to treatment set) 
• A summary of the number and percentage of subjects completed the study and prematurely 
discontinued from the study by reason for study discontinuation (Allocated to treatment set) 
• A summary of the number and percentage of subjects completed the study treatment and 
prematurely discontinued the study treatment before Week 8 visit by reason for 
discontinuation (Safety population).   
 
By-patient listings of disposition details will be provided for all enrolled subjects. 
 
 
7.2. Protocol Deviations 
Number and percentage of subjects with at least one protocol deviation and at least one major 
protocol deviation will be tabulated by category and subcategory and overall (Allocated to 
treatment set). All protocol deviations will be listed (All Enrolled subjects). 
Major protocol violations include but are not limited to: 
• Informed consent not received or provided after the first study visit; 
• Inclusion/exclusion criteria violations in subjects allocated to treatment; 
• Use of prohibited concomitant medication or non-drug therapy that may affect study results 
or their interpretation; 
• Week 4 assessments performed more than 14 days after the scheduled date; 
• Week 8 assessments performed more than 14 days after the scheduled date; 
Major protocol violations will be finalized and approved by MC2 at the data review meeting. 
 
7.3. Demographic and Baseline Variables  
eCRF form: “DEMOGRAPHICS”, “VITAL SIGNS”. 
Descriptive statistics for the following demographic, anthropometric and other baseline 
characteristics will be presented in accordance with section 7: 
− demographic characteristics: country, age, gender, race, ethnic origin; 
− anthropometric characteristics: height (cm), weight (kg), body mass index (BMI, kg/m2); 


 
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eCRF form: “FITZPATRICK SKIN TYPE ASSESSMENT”, “BODY SURFACE AREA 
INVOLVEMENT ASSESSMENT”, “PHYSICIAN’S GLOBAL ASSESSMENT OF PSORIASIS 
SEVERITY”, “MAIN DIAGNOSIS”, “LOCAL SKIN REACTIONS ASSESSMENT”. 
− Fitzpatrick skin type; 
− Scalp BSA psoriatic involvement (%), Neck, Trunk and/or Limbs BSA psoriatic 
involvement (%), Total psoriatic involvement (%); 
− Physician’s Global Assessment of psoriasis severity (PGA); 
− Duration of disease (months); 
Specific calculations and/or conversions include but are not limited to the following: 
Body mass index will be calculated as weight (kg) / [height (m)]2. 
Duration of disease will be calculated in months as (date of informed consent - date of 
diagnosis + 1) / 30.4375. In order to calculate disease duration partial diagnosis date will be 
imputed with 15th day of the same month, if month  and year of diagnosis are collected. If only 
year of diagnosis is collected, diagnosis date will be imputed as July 1st of the corresponding year.  
If the imputed date of diagnosis is later than the date of informed consent, the date of informed 
consent will be used.  
All data will be listed. 
 
7.4. Concurrent Illnesses and Medical Conditions5 
eCRF form: “MEDICAL HISTORY” 
Medical history findings will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA) version 22.0 (or more recent version if available) according to Data MATRIX SOP 
[4], and will be presented by Primary System Organ Class (SOC) and Preferred Term (PT) within 
SOC. 
Prior and concurrent diagnoses will be tabulated separately. 
Medical history findings will be reported on a by-patient basis. This implies that if the subject 
suffered the same event (mapped to same PT) repeatedly the event will be counted once and only 
once for appropriate PT. Within SOC subjects may have reported more than one PT. The SOCs 
and PTs within each SOC will be sorted in descending order of total incidence. 
Classification of condition/diagnosis as either Prior or Concurrent will be based on stop date 
of condition/diagnosis in “MEDICAL HISTORY” eCRF form. The number (%) of subjects 
reporting any medical history will be presented in tables by SOC and PT. 
Medical history records with stop date prior to the date of first dose of study therapy will be 
classified as Prior conditions/diagnoses. If a condition/diagnosis stops on or after the date of first 
 
5 This section is based on the section 7.1 “Demographics and Medical History” of clinical study Protocol. 


 
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dose of study therapy or is ongoing at the end of clinical study, then the condition/diagnosis will 
be classified as Concurrent. If the information about stop date of condition/diagnosis is missing or 
incomplete, the rules from section 6.3 will be applied for classification. Medical history record 
will be assumed to be Concurrent, unless there is clear evidence (through comparison of partial 
dates) to suggest that the condition/diagnosis stopped prior to the first dose of study therapy. If 
there is clear evidence to suggest that the condition/diagnosis stopped prior to the first dose of 
study therapy, the condition/diagnosis will be assumed to be Prior. 
 
All data will be listed. 
 
7.5. Prior and Concurrent Medications6 
eCRF form: “PRIOR/ CONCOMITANT THERAPY AND NON-DRUG THERAPY”. 
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.  
All prior and concomitant medications (including non-drug therapy) will coded using the World 
Health Organization Drug Dictionary (WHODD) version B2 September 2018 (or more recent 
version if available) according to Data MATRIX SOP [4]. The number (%) of subjects reporting 
the use of any prior or concomitant medication will be presented in tables by pharmacological 
subgroup (3rd level) and chemical substance (5th level). Post-treatment medications will be 
reported in listing only. 
Classification of treatment as either Prior, Concomitant or Post-Treatment will be based on start 
and stop date of medication in “PRIOR/CONCOMITANT THERAPY AND NON-DRUG 
THERAPY” eCRF form.  
Medications that stop prior to the date of first dose of study therapy will be classified as Prior 
medications. If a medication stops on or after the date of first dose of study therapy (or 
“ONGOING”) then the medication will be classified as Concomitant unless the medication started 
after the date of last IMP administration in which case it will be classified as Post-Treatment. If 
the information about stop date of medication is missing or incomplete, the rules from section 6.3 
will be applied for classification. Medications will be assumed to be concomitant, unless there is 
clear evidence (through comparison of partial dates) to suggest that the medication stopped prior 
to the first dose of study therapy or started after the last dose of study therapy. If there is clear 
evidence to suggest that the medication stopped prior to the first dose of study therapy, the 
medication will be assumed to be Prior. If there is clear evidence to suggest that the medication 
started after the last dose of study therapy, the medication will be assumed to be Post-Treatment. 
By-patient listings will be provided with appropriate flagging of prior, concomitant and post-
treatment records. 
 
 
6 This section is based on the section 7.2 “Prior and Concomitant Medication” of clinical study Protocol. 


 
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7.6. Prior and Concurrent Procedures 
 
eCRF form: “PRIOR/ CONCOMITANT PROCEDURES”. 
Procedures will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
version 22.0 (or more recent version if available) according to Data MATRIX SOP [4].  
All procedures recorded will be listed. 
 
8. Efficacy Analyses 
Not Applicable. 
9. Safety Analyses 
9.1. Exposure7 
Exposure and compliance will be evaluated based on the information from the “STUDY DRUG 
APPLICATION”, “STUDY DRUG COMPLIANCE”, “STUDY DRUG ACCOUNTABILITY”, 
“END OF TREATMENT”, “MISSING DOSES” eCRF form.  
 
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. 
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.  
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. 
The total duration of exposure is defined as the time interval in days between the first dose and 
the last dose, inclusive, of study drug as [(date of last dose – date of first dose+1)]. 
Total dose (g) administered during the study will be assessed based on study drug 
accountability data as [average weight of tube dispensed –weight of tube returned] summed over 
all tubes dispensed except for tubes assessed as unused or used but lost which will not be taken 
into account in the calculation. Average dispense weight is 75.54 g. 
 
7 This section is based on the section 6.2 “Dosing Regimen” and 6.3 “Dose Modification” of clinical study Protocol. 


 
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 Average weekly dose (g) will be calculated as [total dose (g) / (total duration of exposure / 
7)]. 
Compliance will be estimated as [100% * (number of required days in the time period assessed 
– number of missed doses during the time period assessed)/ number of required days in the time 
period assessed]. The number of required days is the total number of days between the first and 
the last application in the time period assessed excluding days with approved IMP discontinuation.  
If a dose is missed due to approved discontinuation at a given day this day will not be included 
in the calculation of compliance. The period of time between the approved discontinuation at a 
scheduled visit and treatment restart (not inclusive) will not be taken into account in the calculation 
of compliance.  
Treatment compliance will be categorized to less than 80% versus 80% or more. 
Extent of exposure (days) will be calculated as [number of required doses - total number of 
missed doses]. The number of required doses is the total number of days between the first and the 
last application in the time period assessed excluding days with approved IMP discontinuation.  
Number of missed doses will be summarized for subjects with at least one missed dose as a 
continuous variable, both using zero counts for those subjects from Safety Population who have 
not reported any missed dose and providing summary only for those subjects who reported at least 
one missed dose.  
Total duration of exposure (days), total dose (g), weekly dose (g), treatment compliance (%), 
extent of exposure (days), number of missed doses will be summarized by time period (up to Week 
2, up to Week 4 and Week 4 to Week 8) and for the entire treatment period to the Week 8 visit, 
using descriptive statistics in the Safety population.  
The periods that the kits were used as recorded on “STUDY DRUG ACCOUNTABILITY” 
eCRF form will be used to assign the kit to one of the time periods for calculation of total dose (g) 
administered during each period (up to Week 2, up to Week 4 or Week 4 – Week 8). If the use 
period starts at Week 4 or Week 6 visit the time period is Week 4 to Week 8, if the use period 
starts before Week 2 (Week 4) and ends on or before Week 2 (Week 4), the time period is up to 
Week 2 (Week 4), otherwise time period cannot be determined.  
The periods’ start and end date will be defined through the actual dates of subject’s visits. 
Week 2 (Week 4) visit date will be considered the last day of Week 0 – Week 2 (Week 4) period.  
 
All exposure data will be listed by study period. 
 
9.2. Adverse Events 
eCRF form: “ADVERSE EVENTS”. 
All registered AEs will be coded using the MedDRA version 22.0 (or a later version if available). 
Treatment-emergent AEs will be summarized by the overall incidence of at least one event, 
incidence by body system, and incidence by body system and preferred term. Each subject will 
contribute only once (e.g., the first occurrence) to each of the rates, regardless of the number of 
occurrences (events) the subject experiences. Treatment-emergent AEs will be summarized by 


 
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severity (mild, moderate, or severe), and by relationship to trial product (none, possible, probable, 
or definite). An AE is treatment-emergent if its date of onset is on or after the date of the first 
application of the IP. 
Only treatment emergent AEs will be summarized. In the listings, however, all occurrences 
of the AEs will be presented.  
Number (percentage) of subjects and number of AEs will be presented for the Safety 
population in the following tables: 
− All treatment-emergent AE / SAE; 
− Treatment-emergent AE / SAE related to the study drug (relationship to trial product 
assessed by the investigator as possible, probable, or definite including those events where 
assessment is missing); 
− TEAE by maximum severity; 
− TEAE by closest relationship to study drug; 
− TEAE related to study drug by maximum severity; 
− TEAE related to cosyntropin; 
− TEAE related to study procedures; 
− TEAE leading to the permanent discontinuation of study drug (Action taken with IP=“Drug 
withdrawn”); 
− TEAE leading to withdrawal (Did subject withdraw due to this AE?=“Yes”); 
− TEAE leading to death (Outcome = “Death”); 
− Non-serious TEAEs that occurred at a frequency of >= 5% (if no events occurred at the 
5% threshold all non-serious TEAEs will be tabulated). 
This set of tables will be repeated for the adverse events occurring up to Visit 3 / Week 4. 
Treatment-emergent adverse events with start dates on or prior to Visit 3 / Week 4 date will be 
summarized separately. If subject discontinued from the study prior to Visit 3 / Week 4 his/her adverse 
events will also be included in these summaries. If subject missed Visit 3 / Week 4 the planned date of 
visit (study day) will be used to subset the events occurring up to Week 4. 
Tables of TEAEs by maximum severity (closest relationship to study drug) will be prepared 
using the following rules: each SOC / PT category will include only the AEs with the worst severity 
(closest relationship) for each subject. In the Overall category, all AEs of the subjects will be presented. 
Each subject will be counted only once with the worst severity (closest relationship) in each SOC and 
each PT level as well as in the Overall level. 
In case if severity or relationship to study drug is missing, the worst case value will be assumed 
and used in the summary. 
All AEs/SAEs will be listed. Non-treatment emergent adverse events will be identified 
accordingly in the listing. Discontinuations from the trial due to AEs and SAEs will be listed by 
subject. 


 
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9.3. Pregnancies 
eCRF form: “URINE PREGNANCY TEST”, “SERUM 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 1). 
The results of these tests and pregnancies episodes will be reported in the listing. 
 
9.4. Clinical Laboratory Evaluations 
eCRF form: “LABORATORY ASSESSMENT”, “SERUM CHEMISTRY”, “MORNING 
URINE ASSESSMENT”, Central laboratory data. 
Clinical laboratory data will be summarized by presenting shift tables using extended normal 
ranges (baseline to most extreme post-baseline value), by presenting summary statistics of raw data 
and change from baseline values (means, medians, standard deviations (SDs), ranges), and by the 
flagging of notable values (out of range values) in data listings. 
Clinical laboratory evaluations as scheduled in the Table 1 include the following parameters: 
• 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, phosphate, alkaline phosphatase (ALP), plasma parathyroid 
hormone (PTH).  
• 25-OH Vitamin D, only at SV2 
• Morning urine assessment: calcium, phosphate, creatinine, volume, total calcium excretion, 
total phosphate excretion, total creatinine excretion, urinary calcium:creatinine ratio, urinary 
phosphate:creatinine ratio. 
Week 4: If albumin-corrected serum calcium is above the reference range at Week 4, a repeat 
test should be performed at Week 6. 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 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. 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. If the calcium-creatinine ratio is above the reference range at two consecutive visits 
during the trial, 24-hour urine collection must be performed. 
For laboratory parameters the following tables will be presented according to section 7: 
− descriptive statistics of measured values and changes from baseline by visit including 
highest/lowest post-baseline value; 


 
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− shift tables based on comparison with normal range (Low/Normal/High) by visit and to 
highest/lowest post-baseline value; 
− frequency tables for Out of range: Normal/Out of range (Low/High) for laboratory 
parameters by visit. 
Clinical laboratory values will be reported as complete listings of individual subject data. 
A separate listing will be prepared for all clinically significant abnormal results. 
 
9.5. Other Safety Measures 
 
HPA-axis suppression 
The primary outcome variable for HPA axis is serum cortisol level of less than 18 μg/dL (500 
nmol/L) at 30 minutes after ACTH challenge test (at Week 4 and Week 8).  
The number and proportion of subjects with HPA-axis suppression at Week 4 and Week 8 will 
be summarised using frequency counts, percentages and exact 95% CI. Percentage will be 
calculated based on number of valid measurements (number of subjects for whom ACTH 
challenge test was performed) at each post-baseline visit. Number and proportion (95% CI) of 
subjects for whom HPA-axis suppression was noted at least once during the study will be 
presented. For Week 8, number and proportion of subjects with HPA-axis suppression will be 
additionally presented by HPA suppression status at Week 4. 
Serum cortisol level at each time point (pre- and post- ACTH challenge test) will be 
summarized in tables with standard descriptive statistics for continuous variables and 95% CI for 
the means.  
 
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 
 
Descriptive statistics for measured parameters as well as changes from baseline will be 
presented by visit of assessment as scheduled in the Table 1.  
 
Vital signs 
eCRF form: “VITAL SIGNS”. 


 
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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.  
Vital signs (pulse rate (beats/minute), and systolic and diastolic blood pressure (mm Hg), and 
oral or tympanic temperature (ºC)), body weight (kg), body height (cm) and BMI (kg/m2) results will 
be presented in accordance with section 7. 
Vital signs results will be presented by visit of assessment as scheduled in the Table 1.  
Notable ranges are defined for vital signs according to Table 3.1. Notable values are post-
baseline values outside the notable ranges, whether above or below, and are indicated as notably 
abnormal. 
Table 3.1: Definition of Notable Ranges of Vital Signs 
Parameter 
Notable Values and Changes from Baseline 
Systolic blood 
pressure 
90 mmHg or lower and decreased by 20 mmHg or more,  
180 mmHg or greater and increased by 20 mmHg or more 
Diastolic blood 
pressure 
50 mmHg or lower and decreased by 15 mmHg or more,  
110 mmHg or greater and increased by 15 mmHg or more 
Pulse rate 
50 bpm or lower and decreased by 15 bpm or more, 
120 bpm or greater and increased by 15 bpm or more 
 
Normal ranges are defined for vital signs according to Table 3.2.  
 


 
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Table 3.2: Definition of Normal Ranges of Vital Signs 
Parameter 
Units of 
Measure 
Age 
Normal Ranges 
Any 
Low 
High 
Low 
High 
Systolic blood 
pressure 
mmHg 
- 
12 
17 
80 
160 
Diastolic blood 
pressure 
mmHg 
- 
12 
17 
50 
100 
Pulse rate 
Beats/min 
- 
12 
17 
50 
100 
Oral temperature 
°C 
- 
12 
17 
35.0 
37.5 
Tympanic 
temperature 
°C 
- 
12 
17 
35.0 
37.5 
 
 
Vital signs and body weight results will be presented as the following outputs: 
− descriptive statistics for measured values and changes from baseline (vital signs, body 
weight, body height, BMI) by visit and highest/lowest post-baseline assessment (vital 
signs); 
− frequency table for Out of range values, including frequency of Low and High values by 
visit and at any post-baseline assessment (vital signs); 
− frequency table for notably abnormal values and changes from baseline (systolic blood 
pressure, diastolic blood pressure, pulse rate) by visit and at any post-baseline assessment. 
All data will be listed. Notable values will be flagged. 
 
 
ECG 
eCRF form “ELECTROCARDIOGRAM”. 
A 12-lead ECG will be recorded at visits indicated in Table 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.  
Heart rate (beats/min), RR interval (msec), PR interval (msec), QRS duration (msec), QT 
interval (msec), QTC-F interval (msec), QTC-B interval (msec) will be summarized using standard 
descriptive statistics for continuous variables in accordance with section 7. 
Notable ranges are defined for electrocardiogram according to Table 4. Notable values are 
post-baseline values outside the notable ranges and are indicated as notably abnormal. 


 
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Table 4: Definition of Notable Ranges of ECG 
Parameter 
Notable Values and Changes from Baseline 
QTc 
  QTc interval > 450 msec 
 
  QTc interval > 480 msec 
 
  QTc interval > 500 msec 
 
  QTc interval increases from baseline >30 msec 
 
  QTc interval increases from baseline >60 msec 
 
A 12-lead electrocardiogram (ECG) results will be presented in accordance with section 7 by 
visit of assessment as scheduled in the Table 1 as the following outputs: 
− frequency table for Normal/Abnormal clinically significant (Abnormal CS) / Abnormal 
non-clinically significant (Abnormal NCS) evaluation for General assessment (Total 
assessment) by visit and any post-baseline Abnormal and clinically significant Abnormal 
assessment; 
− frequency table for notably abnormal values and changes from baseline (QTC-F interval, 
msec; QTC-B interval, msec) by visit and any post-baseline notably abnormal value;  
− descriptive statistics of ECG parameters and their changes from baseline (Heart rate, 
beats/min; RR interval, msec; PR interval, msec; QRS duration, msec; QT interval, msec; 
QTC-F interval, msec;  QTC-B interval, msec) by visit and highest/lowest post-baseline 
value. 
 
All ECG data will be listed. Notable values will be flagged. 
 
 
Physical examinations 
eCRF form: “PHYSICAL EXAMINATION”. 
An abbreviated physical examination including general appearance, regional lymph nodes and 
a complete dermatological examination of the skin must be performed as scheduled in the Table 1.  
Physical examination / dermatological examination results will be presented in accordance with 
section 7 by visit of assessment as the following output: 
− frequency table for Normal/Abnormal clinically significant (Abnormal CS) / Abnormal 
non-clinically significant (Abnormal NCS) evaluation. 
All physical examination / dermatological examination data will be listed. 
 


 
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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 
provided in Table 7-4 of the protocol. The most severe intensity observed for each category of the 
local skin reaction assessment is to be recorded. 
Local skin reactions (LSR) sum score is defined as the sum of intensity grades across all 
areas and signs per visit. Per sign, the most intense reaction is defined as the maximum intensity 
grade across visits. 
The subject will assess burning and pain after application. The investigator or designee will 
explain the scores provided in Table 7-4 of the Protocol and the subject will tell which one to mark. 
The local skin reaction assessment results will be presented in accordance with section 7 as the 
following outputs: 
− frequency table for investigator assessment of lesional/perilesional area and subject’s 
assessment of burning and pain after application by visit of assessment as scheduled in the 
Table 1 and most severe post-baseline assessment; 
− shift table from baseline to each post-baseline visit value and most severe post-baseline 
value; 
− descriptive statistics of LSR sum scores and their changes from baseline for 
lesional/perilesional area by visit 
 
10. Pharmacokinetics 
Samples for PK analysis will be collected through 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 


 
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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). 
 
All available concentration results will be summarised by analyte and time point using 
appropriate descriptive statistics.  Individual concentration versus time curves will be plotted 
(linear and semi-log plots) using actual time points.  
Measured PK concentrations will be presented using standard descriptive statistics as described 
in section 7. Additionally, geometric mean and CV(%) will be presented. 
Non-quantifiable (BLQ) levels of the analyte will be substituted by LLOQ for descriptive 
summaries and graphical presentation.  
Plasma PK parameters at Week 4 (AUC0-t, AUC0-5, Cmax, and Tmax) will be calculated. The PK 
parameters AUC0-5 and Cmax will be calculated using standard formulas inserting the LLOQ for 
non-quantifiable levels of the analyte. For a given analyte, the PK parameters AUC0-t and Tmax will 
be calculated if at least one post-dose time-point shows a quantifiable level of the analyte. PK 
parameter values will be rounded to the precision of the raw data from which it was derived (Cmax) 
or to 3 significant digits (AUC0-t, AUC0-5). Tmax will be rounded to two decimal places. 
 
Pharmacokinetic Parameters Derivations: 
AUC0-t (pg*h/mL): The area under the curve spanning time interval from 0 to t (up to the last 
time point with measurable concentration above the quantification limit) will be calculated using 
the linear trapezoidal rule based on actual relative time of sampling.  
1) Actual relative time of each sample will be derived as the difference between the datetime 
value of the corresponding sample and the datetime value of drug application, in hours. 
The time of the pre-dose sample will be set to 0. 
2)  For the calculation of AUC0-t BLQ values before the first reported measurable 
concentration (including pre-dose) will be substituted by LLOQ. The BLQ values after the 
last evaluable concentration will be set to missing.  
3) Linear trapezoidal method is used. The area under the curve is defined as the sum of 
trapezoids across all pairs of time points from pre-dose to 5h post-dose at Visit 3 / Week 
4. 
Linear trapezoidal rule: 
The area of the trapezoid between the two data points (t1, C1) and (t2, C2) where C2≥C1 will be 
computed by: 


 
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AUCt1-t2=0.5(t2-t1)(C1+C2). 
AUC0-5 (pg*h/mL): The area under the time-concentration curve from 0 to 5 hours will be 
calculated in a similar way to AUC0-t (pg*h/mL) while imputing the lower limit of quantification 
(LLoQ) for all concentrations below LLoQ. 
Cmax (pg/mL): Individual Cmax values are directly determined from the plasma concentration 
time profiles of each subject as maximum of the observed concentration values after dosing. All 
BLQ values are substituted by LLOQ. 
Tmax (h): The time to attain Cmax. If the same Cmax concentration occurs at different time points, 
Tmax is assigned to the first occurrence of Cmax. If all concentrations are BLQ, Tmax is not calculated. 
The PK parameters will be summarised by analyte using standard descriptive statistics as described 
in section 7. Additionally, geometric mean and CV(%) will be presented for Cmax, AUC0-t and 
AUC0-5. 
11. Other Analyses 
11.1. Physician global assessment 
eCRF form: “PHYSICIAN’S GLOBAL ASSESSMENT OF PSORIASIS SEVERITY”. 
Investigator ratings of disease severity (PGA) will be summarised by trial visit using frequency 
counts and percentages. 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. Only subjects having at least moderate severity at baseline will be included in the 
summary of treatment success. 
PGA results will be presented in accordance with section 7 by visit of assessment as scheduled 
in the Table 1 as the following outputs: 
− descriptive statistics of measured values and changes from baseline by visit; 
− number and proportion (95% CI) of subjects with treatment success, defined as a minimum 
2-point decrease from Baseline in the PGA; 
− Shift table by post-baseline visit compared to baseline for PGA. 
 
11.2. Body surface area involvement 
 
eCRF form: “BODY SURFACE AREA INVOLVEMENT ASSESSMENT”. 
The investigator or designee will assess the extent of the subject’s psoriatic involvement on the 
scalp, neck, trunk and limbs (excluding face, genitals, and intertriginous areas). 


 
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The total psoriatic involvement on the scalp, neck, 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. 
Investigator assessment of BSA involvement for scalp and neck, trunk and/or limbs and total 
BSA involvement will be summarised in accordance with section 7 by visit of assessment as 
scheduled in the Table 1 as the following outputs: 
− descriptive statistics of BSA values and changes from baseline by visit. 
 
11.3. Psoriasis treatment convenience scale 
eCRF form: “PSORIASIS TREATMENT CONVENIENCE SCALE”. 
The aim of PTCS is to assess the impact and convenience of psoriasis treatment. The scale 
consists of 6 disease-specific, self-reported 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? Answered by 1 = very difficult to 10 = very easy.  
2. How greasy was the treatment when applying it to the skin? Answered by 1 = very greasy to 10 = not 
greasy.  
3. How moisturised did your skin feel after applying the treatment? Answered by 1 = not moisturized to 
10 = very moisturized.  
4. How greasy did your skin feel after applying the treatment? Answered by 1 = very greasy to 10 = not 
greasy.  
5. How much did treating your skin disrupt your daily routine? Answered by 1 = very disturbing to 10 = 
not disturbing.  
6. Overall, how satisfied were you with the medical treatment? Answered by 1 = not satisfied to 10 = very 
satisfied. 
 
Ranging from 5 to 50, a PTCS total score is the sum of the scores on questions 1 to 5. If more than 
two questions are not answered, the PTCS total score is missing. If one or two questions remain 
unanswered, the missing scores are replaced by the average of the answered scores for the 
summation. 
 
Psoriasis treatment convenience scale results will be presented by visit of assessment as scheduled 
in the Table 1.  
Psoriasis treatment convenience scale results will be presented by visit as the following 
summaries: 
- 
descriptive statistics for patient ratings by question; 
- 
descriptive statistics for PTCS total score 
 
All ratings will be listed. 
12. Reporting Conventions 


 
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Not Applicable. 
13. Technical Details 
 
Statistical analysis will be performed using SAS 9.4. 
Interim and final statistical analysis report will be prepared in the Microsoft Office Word 
(.docx) format. The results of statistical analysis will be presented in the form of tables, figures 
and listings in English. 
14. Summary of Changes to the Protocol 
Due to small number of subjects at interim analysis  geometric mean values of pharmacokinetic 
parameters will be directly derived from values of PK parameters calculated based on substitution 
of BLQ concentrations with LLOQ rather than estimated using parametric modelling. Median 
concentration – time plots will be omitted. Individual concentration – time plots will be presented 
instead. 
15. References 
1) Committee for Proprietary Medicinal Products (CPMP). International Conference 
on Harmonisation (ICH) Topic E9: Note for Guidance on Statistical Principles for Clinical 
Trials; September 1998. 
2) DataMatrix_SOP_STAT001_Statistical Principles_ver.3.0_June 2019. 
3) DataMatrix_SOP_STAT002_Statistical Analysis Plan Development_ver.2.0_July 
2017. 
4) DataMatrix_SOP_DM010_Dictionary 
Management 
and 
Data 
Coding_ver.2.0_August 2018. 
 
 
 


 
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16. Listing of Tables, Listings and Figures 
16.1. Tables 
Table 14.1.1 Subject Disposition 
 
Table 14.1.2 Violation of Eligibility Criteria 
 
Table 14.1.4 Study Visits 
 
Table 14.1.5.1 Protocol Deviations  
Table 14.1.5.2 Major Protocol Deviations  
Table 14.1.6 Demographic Characteristics 
Table 14.1.7 Other Baseline Characteristics 
Table 14.1.8 Baseline Characteristics by Visit 
Table 14.1.9 Prior Medical Conditions/Diagnoses 
Table 14.1.10 Concurrent Medical Conditions/Diagnoses 
Table 14.1.11 Prior Therapy 
Table 14.1.12 Concomitant Therapy 
Table 14.1.13.1 Summary of Exposure and Compliance 
Table 14.1.13.2 Summary of Exposure and Compliance up to Week 2 
Table 14.1.13.3 Summary of Exposure and Compliance up to Week 4 
Table 14.1.13.4 Summary of Exposure and Compliance from Week 4 to Week 8 
Table 14.2.1.1 Individual and Summarized BDP Plasma Concentrations 
Table 14.2.1.2 Individual and Summarized Betamethasone 17-propionate Plasma Concentrations 
Table 14.2.1.3 Individual and Summarized CAL Plasma Concentrations 
Table 14.2.1.4 Individual and Summarized MC1080 Plasma Concentrations 
Table 14.2.2 Summary of Pharmacokinetic Parameters 
Table 14.3.1.1 Overall Summary of TEAEs 
Table 14.3.1.2.1 Incidence of Treatment-emergent Adverse Events 
Table 14.3.1.2.2 Incidence of Treatment-emergent Adverse Events up to Week 4 
Table 14.3.1.3.1 Incidence of Treatment-emergent Adverse Events Related to the Study Drug 
Table 14.3.1.3.2 Incidence of Treatment-emergent Adverse Events Related to the Study Drug up 
to Week 4 
Table 14.3.1.4.1 Incidence of Serious Treatment-emergent Adverse Events 
Table 14.3.1.4.2 Incidence of Serious Treatment-emergent Adverse Events up to Week 4 
Table 14.3.1.5.1 Incidence of Serious Treatment-emergent Adverse Events Related to the Study 
Drug 
Table 14.3.1.5.2 Incidence of Serious Treatment-emergent Adverse Events Related to the Study 
Drug up to Week 4 
Table 14.3.1.6.1 Incidence of Treatment-emergent Adverse Events by Maximum Severity 
Table 14.3.1.6.2 Incidence of Treatment-emergent Adverse Events up to Week 4 by Maximum 
Severity 
Table 14.3.1.7.1 Incidence of Treatment-Emergent Adverse Events by Closest Relationship 
Table 14.3.1.7.2 Incidence of Treatment-Emergent Adverse Events up to Week 4 by Closest 
Relationship 
Table 14.3.1.8.1 Incidence of Treatment-emergent Adverse Events Leading to Discontinuation 
of Study Drug  
Table 14.3.1.8.2 Incidence of Treatment-emergent Adverse Events Leading to Discontinuation 
of Study Drug up to Week 4 
Table 14.3.1.9.1 Incidence of Treatment-emergent Adverse Events Leading to Withdrawal 


 
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Table 14.3.1.9.2 Incidence of Treatment-emergent Adverse Events Leading to Withdrawal up to 
Week 4 
Table 14.3.1.10.1 Incidence of Non-serious treatment-emergent Adverse Events Occurred at a 
Frequency of >=5% 
Table 14.3.1.10.2 Incidence of Non-serious treatment-emergent Adverse Events Occurred at a 
Frequency of >=5% up to Week 4 
Table 14.3.1.11 Incidence of Treatment-emergent Adverse Events Related to Cosyntropin 
Table 14.3.1.12 Incidence of Treatment-emergent Adverse Events Related to Study Procedures 
Table 14.3.2.1 Incidence of Treatment-emergent Adverse Events Leading to Death 
Table 14.3.2.2 Incidence of Treatment-emergent Adverse Events Related to the Study Drug and 
Leading to Death 
Table 14.3.4.1.1 Summary of ACTH Challenge Test 
Table 14.3.4.1.2 Incidence of HPA Axis Suppression 
 
Table 14.3.4.2.1 Summary of Calcium Metabolism Evaluation 
Table 14.3.4.3.1 Summary of Hematology Parameters 
Table 14.3.4.3.2 Summary of Blood Chemistry Parameters 
Table 14.3.4.3.3 Summary of Morning Urine Assessment Parameters 
Table 14.3.4.4.1 Hematology Shifts from Baseline 
Table 14.3.4.4.2 Blood Chemistry Shifts from Baseline 
Table 14.3.4.4.3 Morning Urine Assessment Shifts from Baseline 
Table 14.3.4.5.1 Incidence of Hematology Assessments Outside of Normal Range 
Table 14.3.4.5.2 Incidence of Blood Chemistry Assessments Outside of Normal Range 
Table 14.3.4.5.3 Incidence of Morning Urine Assessments Outside of Normal Range 
Table 14.3.4.6.1 Summary of Local Skin Reactions Assessment 
Table 14.3.4.6.2 Local Skin Reactions Assessment Shifts from Baseline 
Table 14.3.4.6.3 Summary of LSR Sum Score 
 
Table 14.3.4.7.1 Summary of Vital Signs 
Table 14.3.4.7.2 Incidence of Vital Signs Assessments Outside of Normal Range 
Table 14.3.4.7.3 Incidence of Notably Abnormal Vital Signs Assessments 
Table 14.3.4.8 Summary of Physical Parameters 
Table 14.3.4.9 Summary of Physical Examination 
Table 14.3.4.10.1 Summary of Electrocardiogram 
Table 14.3.4.10.2 Incidence of Abnormal ECG Assessments 
Table 14.3.4.10.3 Incidence of Notably Abnormal ECG Assessments 
Table 14.4.1.1 Summary of PGA 
Table 14.4.1.2 Summary of Treatment Success 
Table 14.4.1.3 PGA Shifts from Baseline 
Table 14.4.2.1 Summary of Body Surface Area Involvement 
 
Table 14.4.3.1 Summary of Psoriasis Treatment Convenience Scale 
 
 
16.2. Figures 
Figure 16.2.5.4 Individual BDP Plasma Concentration-time Profiles on Linear and Semi-
logarithmic Scales Week 4 
Figure 16.2.5.5 Individual Calcipotriol (CAL) Plasma Concentration-time Profiles on Linear and 
Semi-logarithmic Scales Week 4 


 
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Figure 16.2.5.6 individual MC1080 Plasma Concentration-time Profiles on Linear and Semi-
logarithmic Scales Week 4 
Figure 16.2.5.7 individual Betamethasone 17-propionate, Plasma Concentration-time Profiles on 
Linear and Semi-logarithmic Scales Week 4 
 
 
16.3. Listings 
Listing 16.2.1.1 Analysis Populations 
Listing 16.2.1.2 Subject Visits 
Listing 16.2.1.3 Study Completion 
Listing 16.2.1.4 Study Treatment Completion 
Listing 16.2.2.1 Violation of Inclusion/Exclusion Criteria 
Listing 16.2.2.2 Protocol Deviations 
Listing 16.2.4.1 Demographics and Other Baseline Characteristics 
Listing 16.2.4.2 Baseline Variables 
Listing 16.2.4.3 Medical History 
Listing 16.2.4.4 Prior/Concomitant Therapy 
Listing 16.2.4.5 Prior/Concomitant Procedures 
Listing 16.2.5.1 Exposure 
Listing 16.2.5.2 Study Drug Compliance 
Listing 16.2.5.3 Missed Doses 
Listing 16.2.5.4 Study Drug Accountability 
Listing 16.2.7.1 Adverse Events 
Listing 16.2.7.2 Serious Adverse Events 
Listing 16.2.7.3 Listing of Adverse Events Leading Discontinuation of Study Drug 
Listing 16.2.7.4 Listing of Adverse Events Leading to Withdrawal 
Listing 16.2.8.1 Hematology in SI Units 
Listing 16.2.8.2 Serum Biochemistry in SI Units 
Listing 16.2.8.3 Morning Urine Assessment in SI Units 
Listing 16.2.8.4 24-hour Urine Assessment 
Listing 16.2.8.5 Serum Pregnancy Test 
Listing 16.2.8.6 Urine Pregnancy Test 
Listing 16.2.8.7 ACTH Challenge Test 
Listing 16.2.8.8 Clinically Significant Laboratory Abnormalities 
Listing 16.2.9.1 Food Diary. Calcium-rich Nutrients Consumption 
Listing 16.2.9.2 Local Skin Reactions Assessment 
Listing 16.2.9.3 Vital Signs 
Listing 16.2.9.4 Electrocardiogram 
Listing 16.2.9.5 Physical Parameters 
Listing 16.2.9.6 Physical Examination 
Listing 16.2.9.7 Physician Global Assessment of Psoriasis Severity 
Listing 16.2.9.8 Body Surface Area Involvement 
Listing 16.2.9.9 Psoriasis Treatment Convenience Scale 
Listing 16.2.9.10 Pharmacokinetic Concentrations 
Listing 16.2.9.11 Pharmacokinetic Parameters 
 
 


 
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Appendix 1. TFLs Shells 
Tables Shells 
Subject Disposition 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.1 Subject Disposition 
All Enrolled subjects 
Page Х of Х 
 
 
Total 
(N = XX) 
n (%) 
 
 
Subjects who provided the informed consent / informed assent 
XX 
Screening Failures [1] 
XX 
  Reasons for premature discontinuation 
 
    Inconsistency with inclusion / exclusion criteria 
XX 
    Withdrawal of informed consent / informed assent 
XX 
    ... 
XX 
 
 
Allocated to Treatment 
XX 
Safety Population 
XX 
HPA Population 
XX (XX.X) 
PK Population 
XX (XX.X) 
 
 
Completed the Study 
XX (XX.X) 
Discontinued the Study Prematurely 
XX (XX.X) 
  Reasons for premature discontinuation 
 
    Inconsistency with inclusion / exclusion criteria 
XX (XX.X) 
    Lost to follow-up 
XX (XX.X) 
    Withdrawal of informed consent / informed assent 
XX (XX.X) 
    Intake of a prohibited medication(s) 
XX (XX.X) 
    Pregnancy 
XX (XX.X) 
    Adverse event / Serious adverse event 
XX (XX.X) 
    Investigator’s discretion 
XX (XX.X) 
    Sponsor’s decision to terminate the study 
XX (XX.X) 


 
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    Termination of the study by the Regulatory Authority 
XX (XX.X) 
      Other 
XX (XX.X) 
        Other reason 1 
XX (XX.X) 
        Other reason 2 
XX (XX.X) 
        ... 
XX (XX.X) 
 
 
Discontinued Treatment before Week 8 visit 
XX (XX.X) 
  Primary reason for treatment discontinuation 
XX (XX.X) 
    Subject classified as clear at any of the on-treatment visits 
XX (XX.X) 
    HPA axis suppression is noted at Week 4 
XX (XX.X) 
   Premature study termination 
XX (XX.X) 
   Adverse event / Serious adverse event 
XX (XX.X) 
   Investigator’s discretion 
XX (XX.X) 
   Other 
XX (XX.X) 
     Other reason 1 
XX (XX.X) 
     Other reason 2 
XX (XX.X) 
     ... 
XX (XX.X) 
 
 
 
HPA=Hypothalamic-pituitary-adrenal; PK=Pharmacokinetics. 
[1] Including subjects who satisfied inclusion/exclusion criteria but who were not allocated to treatment (no drug dispensed). 
N: the number of subjects in the All Enrolled subjects set. 
n: the number of subjects within a specific category. Percentages are calculated based on the number of subjects in the Safety  
population. 
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. 
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. 
HPA population: all subjects in the Safety population that show normal HPA function at SV2. 
 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings/ Datasets used/ Referenced Data Listings  
 
 
 
 
 
 


 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.1.2 Violation of Eligibility Criteria 
Screening Failures 
Page Х of Х 
 
 
Total 
(N = XX) 
n 
Subjects with any violation of eligibility criteria 
XX 
 
 
Subjects with any violation of inclusion criteria 
XX 
  Inclusion criterion #1  
XX 
  Inclusion criterion #2 
XX 
  ... 
... 
 
 
Subjects with any violation of exclusion criteria 
XX 
  Exclusion criterion #1 
XX 
  Exclusion criterion #2 
XX 
  ... 
... 
 
Inclusion criterion #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.  
N: the number of Screening Failures. 
n: the number of subjects within a specific category.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming Note: Report only the criteria violated. If no criteria are violated suppress the printing of subsequent rows. Include description of all the 
criteria violated in the footnote. 
 


 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.1.4 Study Visits 
Allocated to treatment set 
Page Х of Х 
 
 
Total 
(N = XX) 
n (%) 
 
 
Screening Visit 1 (Days -42 to -8) 
XX (XX.X) 
Screening Visit 2 (Days -7 to -4) 
XX (XX.X) 
Visit 1 (Day 0) 
XX (XX.X) 
Visit 2 / Week 2 (Day 14 +/- 2) 
XX (XX.X) 
Visit 3 / Week 4 (Day 28 +/- 2) 
XX (XX.X) 
Visit 4 / Week 6 (Day 42 +/- 2) 
XX (XX.X) 
Visit 5 / Week 8 (Day 56 +/- 2) 
XX (XX.X) 
Follow-up Visit [1] 
XX (XX.X) 
Early Termination Visit 
XX (XX.X) 
 
 
 
 
 
[1] 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. 
 
N: the number of subjects in the Allocated to treatment set. 
n: the number of subjects within a specific category. Percentages are calculated as (100 x n/N). 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
 


 
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Protocol Deviations 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.5.1 Protocol Deviations 
Allocated to treatment set 
Page Х of Х 
 
 
Total 
(N = XX) 
n (%) 
 
 
Subjects with at least one protocol deviation 
XX (XX.X) 
 
 
  Deviation category #1 
XX (XX.X) 
    Deviation subcategory #1 
XX (XX.X) 
    Deviation subcategory #2 
XX (XX.X) 
    ... 
 
 
 
  Deviation category #2 
XX (XX.X) 
    Deviation subcategory #1 
XX (XX.X) 
    Deviation subcategory #2 
XX (XX.X) 
    ... 
 
 
 
 
N: the number of subjects in the Allocated to treatment set. 
n: the number of subjects with at least one protocol deviation. Percentages are calculated as (100 x n/N). 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Similar to table 14.1.5.1, the following tables will be constructed (with corrections of underlined fragments in the footnote: “n: the number of 
subjects with at least one major protocol deviation.” 
 
Table 14.1.5.2 Major Protocol Deviations 
 
 


 
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Demographic Characteristics 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.6 Demographic Characteristics 
Safety population 
Page Х of Х 
 
 
 
Total 
(N = XX) 
 
 
 
Country 
 
 
  n 
 
XX 
  Czech Republic 
n (%) 
XX (XX.X) 
  Germany 
n (%) 
XX (XX.X) 
  Hungary 
n (%) 
XX (XX.X) 
 
 
 
Age (full years) 
 
 
  n 
 
XX 
  Mean 
 
XX.X 
  SD 
 
XX.X 
  Median 
 
XX.X 
  Q1, Q3 
 
XX.X, XX.X 
  Min, Max 
 
XX.X, XX.X 
 
 
 
Sex  
 
 
  n 
 
XX 
  Male 
n (%) 
XX (XX.X) 
  Female 
n (%) 
XX (XX.X) 
  Unknown 
n (%) 
XX (XX.X) 
 
 
 
Ethnic origin 
 
 
  n 
 
XX 
  Hispanic or Latino 
n (%) 
XX (XX.X) 
  Not Hispanic or Latino 
n (%) 
XX (XX.X) 
  Unknown 
n (%) 
XX (XX.X) 
 
 
 
Race 
 
 
  n 
 
XX 
  American Indian or Alaska Native 
n (%) 
XX (XX.X) 
  Asian 
n (%) 
XX (XX.X) 
  Black or African American 
n (%) 
XX (XX.X) 
  Native Hawaiian or Other Pacific Islander 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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  White 
 
 
  Other / Multiple 
n (%) 
XX (XX.X) 
    Other race 1 
n (%) 
XX (XX.X) 
    Other race 2 
n (%) 
XX (XX.X) 
    ... 
... 
... 
  Unknown 
n (%) 
XX (XX.X) 
 
 
 
 
 
 
 
N: the number of subjects in the Safety population. 
n: the number of valid measurements or the number of subjects within a specific category. Percentages are calculated as (100 x n/N). 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
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Baseline Variables 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.7 Other Baseline Characteristics 
Safety population 
Page Х of Х 
 
 
 
Total 
(N = XX) 
 
 
 
Fitzpatrick skin type 
 
 
  n 
 
XX 
  I - Pale white skin, blue/hazel eyes, blond/red hair (Always burns, does not 
tan) 
n (%) 
XX (XX.X) 
  II - Fair skin, blue eyes (Burns easily, tans poorly) 
n (%) 
XX (XX.X) 
  III - Darker white skin (Tans after initial burn) 
n (%) 
XX (XX.X) 
  IV - Light brown skin (Burns minimally, tans easily) 
n (%) 
XX (XX.X) 
  V - Brown skin (Rarely burns, tans darkly easily) 
n (%) 
XX (XX.X) 
  VI - Dark brown or black skin (Never burns, always tans darkly) 
n (%) 
XX (XX.X) 
  Unknown 
n (%) 
XX (XX.X) 
 
 
 
... 
... 
... 
 
 
 
 
N: the number of subjects in the Safety population. 
n: the number of valid measurements or the number of subjects within a specific category. Percentages are calculated as (100 x n/N). 
Duration of disease is calculated in months as (date of diagnosis – date of informed consent + 1) / 30.4375. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming Note: Continue table for the following parameters:  
 
− Duration of disease (months) (Continuous); 
− Previous treatment (Biologics and systemic [TNF-a inhibitors, IL-12/23 inhibitors, IL-17 inhibitors, Fumarate, Other], Phototherapy (UVA or 
PUVA), Topical: fixed combination corticosteroid plus vitamin D analogs, Topical: corticosteroids, Topical: retinoids, Topical: salicylic acid, 
Topical: vitamin D analogs, Topical: calcineurin inhibitors, Topical: tar, Other). 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.1.8 Baseline Characteristics by Visit 
Safety population 
Page Х of Х 
Parameter: Physician global assessment of psoriasis severity (categorical) 
Visit 
Total 
(N = XX) 
n (%) 
 
 
Screening V1 
 
  n 
XX 
  0 - Clear 
XX (XX.X) 
  1 – Almost Clear 
XX (XX.X) 
  2 - Mild 
XX (XX.X) 
  3 - Moderate 
XX (XX.X) 
  4 - Severe 
XX (XX.X) 
 
 
Screening V2 
 
  n 
XX 
  0 - Clear 
XX (XX.X) 
  1 – Almost Clear 
XX (XX.X) 
  2 - Mild 
XX (XX.X) 
  3 - Moderate 
XX (XX.X) 
  4 - Severe 
XX (XX.X) 
 
 
Visit 1 (Day 0) 
 
  n 
XX 
  0 - Clear 
XX (XX.X) 
  1 – Almost Clear 
XX (XX.X) 
  2 - Mild 
XX (XX.X) 
  3 - Moderate 
XX (XX.X) 
  4 - Severe 
XX (XX.X) 
 
 
Baseline [1] 
 
  n 
XX 
  0 - Clear 
XX (XX.X) 
  1 – Almost Clear 
XX (XX.X) 
  2 - Mild 
XX (XX.X) 
  3 - Moderate 
XX (XX.X) 
  4 – Severe 
XX (XX.X) 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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BMI=Body Mass Index; BSA=Body Surface Area; PGA= Physician Global Assessment. 
N: the number of subjects in the Safety population. 
n: the number of subjects within a specific category or the number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
[1] Baseline is the last non-missing assessment prior to the first dose of the study drug. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings  
 
Programming note: 
Report the following visits: Screening V1, Screening V2, Visit 1 (Day 0), Baseline (where applicable). 
Continue table for the following parameters:  
− Physician global assessment of psoriasis severity (continuous); 
− Height (cm); 
− Weight (kg);  
− Body mass index (BMI, kg/m2); 
− Systolic blood pressure (mm Hg); 
− Diastolic blood pressure (mm Hg); 
− Pulse (beats/min); 
− Oral temperature (C);  
− Tympanic temperature (C); 
− 25-Hydroxyvitamin D3 (ug/L); 
− Serum Calcium Corrected for Albumin (mmol/L); 
− Scalp BSA psoriatic involvement (%); 
− Neck, Trunk and/or Limbs BSA psoriatic involvement (%); 
− Total psoriatic involvement (%); 
− Serum cortisol pre-stimulation (nmol/L);  
− Serum cortisol post-stimulation (nmol/L); 
− Investigator assessment of Erosion/ulceration in lesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)); 
− Investigator assessment of Vesicles in lesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe));  
− Investigator assessment of Erythema in perilesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)); 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
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− Investigator assessment of Scaling in the perilesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)); 
− Investigator assessment of Edema in perilesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)); 
− Investigator assessment of Atrophy in perilesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)); 
− Investigator assessment of Vesicles in perilesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)); 
− Investigator assessment of Erosion/ulceration in perilesional area (0 (Absent), 1 (Mild), 2 (Moderate), 3 (Severe)). 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Medical History 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.9 Prior Medical Conditions/Diagnoses 
Safety population 
Page Х of Х 
 
System Organ Class (SOC)   
    Preferred Term (PT) 
       
Total 
(N = XX) 
n (%) 
Overall 
XX (XX.X) 
 
 
System Organ Class 1 
XX (XX.X) 
  Preferred Term 1 
XX (XX.X) 
  Preferred Term 2 
XX (XX.X) 
      ... 
... 
System Organ Class 2 
XX (XX.X) 
  Preferred Term 1 
XX (XX.X) 
  Preferred Term 2 
XX (XX.X) 
      ... 
... 
 
 
... 
... 
 
MedDRA=Medical Dictionary for Regulatory Activities. 
N: the number of subjects in the Safety population. 
n: the number of subjects with at least one medical history event within a specific category. Percentages are calculated as (100 x n/N). 
Conditions/diagnoses are classified as 'Prior' if the condition/diagnosis end date is prior to study treatment start date or the subject did not 
receive any study treatment. 
Medical history events are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note: System organ classes (SOC) and preferred terms (PT) within each SOC are sorted in descending order of n(%). 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Similar to table 14.1.9, the following table will be constructed (with corrections of underlined footnote: “Conditions/diagnoses are classified as 
'Concurrent' if the condition/diagnosis end date is on or after the study treatment start date”) for the Safety population: 
 
Table 14.1.10 Concurrent Medical Conditions/Diagnoses 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
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Prior and Concomitant therapy 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.11 Prior Therapy 
Safety population 
Page Х of Х 
 
Pharmacological subgroup (3rd level) 
  Chemical substance (5th level) 
Total 
(N = XX) 
n (%) 
Overall 
XX (XX.X) 
 
 
Pharmacological subgroup 1 
XX (XX.X) 
  Chemical substance 1 
XX (XX.X) 
  Chemical substance 2 
XX (XX.X) 
  ... 
 
Pharmacological subgroup 2 
XX (XX.X) 
  Chemical substance 1 
XX (XX.X) 
  Chemical substance 2 
XX (XX.X) 
  ... 
 
  
... 
 
N: the number of subjects in the Safety population. 
n: the number of subjects with at least one prior medication within a specific category. Percentages are calculated as (100 x n/N). 
Medications are classed as 'Prior' if the medication end date is prior to study treatment start date or the subject did not receive any study 
treatment. 
Medications are coded by WHO drug dictionary version XX.X. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note: The pharmacological subgroups and chemical substances within each pharmacological subgroup are sorted in descending order 
of n (%). Each subject is counted only once per pharmacological subgroup and once per chemical substance. 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Similar to table 14.1.11, the following table will be constructed (with corrections of underlined fragments in the footnote: “Medication is classified 
as 'Concomitant' if either the medication start date is on or after study treatment start date and on or prior to study treatment end date, or the medication 
start date is before the study treatment end date and the medication end date is on or after the study treatment start date.” for the Safety population: 
 
Table 14.1.12 Concomitant Therapy 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
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Exposure 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.1.13.1 Summary of Exposure and Compliance 
Safety population 
Page Х of Х 
 
 
 
Total 
(N = XX) 
 
 
 
Total duration of exposure (days) 
 
 
  n 
 
XX 
  Mean 
 
XX.X 
  SD 
 
XX.X 
  Median 
 
XX.X 
  Q1, Q3 
 
XX.X, XX.X 
  Min, Max 
 
XX, XX 
 
 
 
Extent of exposure (days) 
 
 
  n 
 
XX 
  Mean 
 
XX.X 
  SD 
 
XX.X 
  Median 
 
XX.X 
  Q1, Q3 
 
XX.X, XX.X 
  Min, Max 
 
XX, XX 
 
 
 
Compliance (%) 
 
 
  n 
 
XX 
  Mean 
 
XX.XX 
  SD 
 
XX.XX 
  Median 
 
XX.XX 
  Q1, Q3 
 
XX.XX, XX.XX 
  Min, Max 
 
XX.X, XX.X 
 
 
 
Compliance category 
 
 
  < 80% 
n (%) 
XX (XX.X) 
  >= 80% 
n (%) 
XX (XX.X) 
 
 
 
Average weekly dose (g) 
 
 
  n 
 
XX 


 
SF_STAT001_ver 2_Eng 
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  Mean 
 
XX.XX 
  SD 
 
XX.XX 
  Median 
 
XX.XX 
  Q1, Q3 
 
XX.XX, XX.XX 
  Min, Max 
 
XX.X, XX.X 
 
 
 
Total dose (g) 
 
 
  n 
 
XX 
  Mean 
 
XX.XX 
  SD 
 
XX.XX 
  Median 
 
XX.XX 
  Q1, Q3 
 
XX.XX, XX.XX 
  Min, Max 
 
XX.X, XX.X 
 
 
 
Number of missed doses (subjects with at least 1 missed dose) [1] 
 
 
  n 
 
XX 
  Mean 
 
XX.X 
  SD 
 
XX.X 
  Median 
 
XX.X 
  Q1, Q3 
 
XX.X, XX.X 
  Min, Max 
 
XX, XX 
 
 
 
Number of missed doses (including zero counts) [2] 
 
 
  n 
 
XX 
  Mean 
 
XX.X 
  SD 
 
XX.X 
  Median 
 
XX.X 
  Q1, Q3 
 
XX.X, XX.X 
  Min, Max 
 
XX, XX 
 
N: the number of subjects in the Safety population. 
n: the number of valid measurements or the number of subjects within a specific category. Percentages are calculated as (100 x n/N). 
Total duration of exposure (days) is defined as (date of the last dose – date of the first dose + 1). 
Total dose (g) is assessed as (weight of the tube dispensed – weight of the tube returned) summed over all tubes used and returned. Lost and unused 
tubes were not accounted for in the calculation of total dose. 
Extent of exposure (days) is defined as (number of required days – number of missed doses).  
Compliance is estimated as [100% * (number of required days – number of missed doses)/ number of required days].  
Periods of approved discontinuations are not taken into account in the calculation of extent of exposure and compliance. 
[1] Only subjects with at least one missed dose were included into this summary. 
[2] Subjects with no missed doses during the period are included with zero counts. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Similar to table 14.1.13.1, the following tables will be constructed: 
 
 
Table 14.1.13.2 Summary of Exposure and Compliance up to Week 2 
Table 14.1.13.3 Summary of Exposure and Compliance up to Week 4 
Table 14.1.13.4 Summary of Exposure and Compliance from Week 4 to Week 8 


 
SF_STAT001_ver 2_Eng 
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MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Pharmacokinetics Analyses 
MC2 Therapeutics 
MC2-01-C6 
Table 14.2.1.1 Individual and Summarized BDP Plasma Concentrations 
PK population 
Page Х of Х 
 
Subject Number/ 
Statistic 
SV2 
Week 2  
pre-dose 
Week 4  
pre-dose 
1h 
3h 
5h 
Week 8  
pre-dose 
 
 
 
 
 
 
 
 
XXXXXXXXXXXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XXXXXXXXXXXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XXXXXXXXXXXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XXXXXXXXXXXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
... 
 
 
 
 
 
 
 
XXXXXXXXXXXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
XX.XXX 
 
 
 
 
 
 
 
 
n 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
nquant 
XX 
XX 
XX 
XX 
XX 
XX 
XX 
Mean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
SD 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
gMean 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
gCV(%) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Median 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
Q1, Q3 
XX.X, XX.XX 
XX.X, XX.XX 
XX.X, XX.XX 
XX.X, XX.XX 
XX.X, XX.XX 
XX.X, XX.XX 
XX.X, XX.XX 
Min, Max 
XX.XX, XX.X 
XX.XX, XX.X 
XX.XX, XX.X 
XX.XX, XX.X 
XX.XX, XX.X 
XX.XX, XX.X 
XX.XX, XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BDP=Betamethasone dipropionate; BLQ=Below Limit of Quantification; gCV=Geometric Coefficient of Variation; gMean=Geometric Mean; LLOQ=Lower Limit of 
Quantification; PK=Pharmacokinetic. 
BLQ concentrations were substituted with LLOQ for the calculation of summary statistics. LLOQ for BDP is XX.X pg/mL. 
The unit of concentration is pg/mL. 
n: the number of valid measurements; nquant: number of measurements with quantifiable level of analyte. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Similar to table 14.2.1.1, the following tables will be constructed (with modification of underlined fragments): 
 


 
SF_STAT001_ver 2_Eng 
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Table 14.2.1.2 Individual and Summarized Betamethasone 17-propionate Plasma Concentrations 
Table 14.2.1.3 Individual and Summarized CAL Plasma Concentrations  
Table 14.2.1.4 Individual and Summarized MC1080 Plasma Concentrations 
 
Programming note:  
Change the corresponding footnote to “CAL=Calcipotriene (Calcipotriol)”. 
 
 


 
SF_STAT001_ver 2_Eng 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.2.2 Summary of Pharmacokinetic Parameters 
PK population 
Page Х of Х 
Analyte: Betamethasone dipropionate (BDP) 
 
Total 
(N = XX) 
 
 
Cmax (pg/mL) 
 
  n 
XX 
  Mean 
XX.XX 
  SD 
XX.XX 
  gMean 
XX.XX 
  gCV(%) 
XX.X 
  Median 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
  Min, Max 
XX.XX, XX.XX 
 
 
AUC0-5 (pg*h/mL) 
 
  n 
XX 
  Mean 
XX.XX 
  SD 
XX.XX 
  gMean 
XX.XX 
  gCV(%) 
XX.X 
  Median 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
 
 
AUC0-t (pg*h/mL) 
 
  n 
XX 
  Mean 
XX.XX 
  SD 
XX.XX 
  gMean 
XX.XX 
  gCV(%) 
XX.X 
  Median 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
 
 
Tmax (h) 
 
  n 
XX 
  Mean 
XX.XX 
  SD 
XX.XX 


 
SF_STAT001_ver 2_Eng 
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  Median 
XX.XX 
  Q1, Q3 
X.XX, X.XX 
  Min, Max 
X.XX, X.XX 
 
 
 
AUC= Area under the time-concentration curve; BDP=Betamethasone dipropionate; CAL=Calcipotriene (Calcipotriol); Cmax= Maximum plasma drug concentration; 
gCV=Geometric Coefficient of Variation; gMean=Geometric Mean; PK=Pharmacokinetic; Tmax= Time to maximum plasma drug concentration.  
N: the number of subjects in the PK population. 
n: the number of valid measurements. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note: 
Continue table for the following analytes:  
− Betamethasone 17-propionate; 
− Calcipotriene (Calcipotriol, CAL); 
− MC1080.  
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
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Safety Analyses 
Adverse Events 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.1.1 Overall Summary of TEAEs 
Safety population 
Page Х of Х 
 
 
Total 
(N = XX) 
n (%) / E 
 
 
Any TEAE 
XX (XX.X) / XX 
Any TEAE related to study treatment 
XX (XX.X) / XX 
Any TEAE related to study procedures 
XX (XX.X) / XX 
Any TEAE related to Cosyntropin 
XX (XX.X) / XX 
Any Serious TEAE 
XX (XX.X) / XX 
Any Serious TEAE related to study treatment 
XX (XX.X) / XX 
Any TEAE leading to study treatment discontinuation 
XX (XX.X) / XX 
Any TEAE leading to withdrawal 
XX (XX.X) / XX 
 
 
Maximum Severity 
 
  Mild 
XX (XX.X) 
  Moderate 
XX (XX.X) 
  Severe 
XX (XX.X) 
 
 
Strongest Causal Relationship to Study Treatment 
 
  Not related  
XX (XX.X) 
  Possibly related 
XX (XX.X) 
  Probably related 
XX (XX.X) 
  Definitely related 
XX (XX.X) 
 
 
 
AE=Adverse Event; TEAE=Treatment-Emergent Adverse Event. 
N: the number of subjects in the Safety population. 
n: the number of subjects with at least one TEAE within a specific category. Percentages are calculated as (100 x n/N). 
E: total number of TEAEs reported within a specific category. 
A TEAE is defined as an AE that started after the first dose of the study treatment. 
If the severity is missing for a TEAE, then ‘Severe’ category is assigned. 
If the relationship is missing for a TEAE, then ‘Definitely related’ category is assigned. 


 
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Subjects with more than one TEAE will be counted once in the maximum severity or strongest relationship category. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 


 
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Approval Date 19 July 2017 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.3.1.2.1 Incidence of Treatment-emergent Adverse Events 
Safety population 
Page Х of Х 
 
System Organ Class (SOC) 
  Preferred Term (PT) 
Total 
(N = XX) 
n (%) / E 
Overall 
XX (XX.X) / XX 
 
 
System Organ Class 1 
XX (XX.X) / XX 
  Preferred Term 1 
XX (XX.X) / XX 
  Preferred Term 2 
XX (XX.X) / XX 
  ... 
 
System Organ Class 2 
XX (XX.X) / XX 
  Preferred Term 1 
XX (XX.X) / XX 
  Preferred Term 2 
XX (XX.X) / XX 
  ... 
... 
 
AE=Adverse Event; MedDRA=Medical Dictionary for Regulatory Activities; TEAE=Treatment-Emergent Adverse Event. 
N: the number of subjects in the Safety population. 
n: the number of subjects with at least one TEAE within a specific category. Percentages are calculated as (100 x n/N). 
E: total number of TEAEs reported within a specific category. 
Adverse events are coded by MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  
System organ classes (SOC) and preferred terms (PT) within each SOC should be sorted in descending order of n (%). 
Each subject is counted only once per preferred term (РТ) and once per system organ class (SOC). 
 
 
 


 
SF_STAT001_ver 2_Eng 
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Similar to table 14.3.1.2.1, the following tables will be constructed (with the corresponding corrections of underlined fragments in the note): 
 
 
Table 14.3.1.2.2 Incidence of Treatment-emergent Adverse Events up to Week 4 
Table 14.3.1.3.1 Incidence of Treatment-emergent Adverse Events Related to the Study Drug 
Table 14.3.1.3.2 Incidence of Treatment-emergent Adverse Events Related to the Study Drug up to Week 4 
Table 14.3.1.4.1 Incidence of Serious Treatment-emergent Adverse Events 
Table 14.3.1.4.2 Incidence of Serious Treatment-emergent Adverse Events up to Week 4 
Table 14.3.1.5.1 Incidence of Serious Treatment-emergent Adverse Events Related to the Study Drug 
Table 14.3.1.5.2 Incidence of Serious Treatment-emergent Adverse Events Related to the Study Drug up to Week 4 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
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MC2 Therapeutics 
MC2-01-C6 
Table 14.3.1.6.1 Incidence of Treatment-emergent Adverse Events by Maximum Severity 
Safety population 
Page Х of Х 
 
System Organ Class (SOC) 
  Preferred Term (PT) 
Severity 
 
Total 
(N = XX) 
n (%) / E 
Overall 
Mild 
 
XX (XX.X) / XX 
 
Moderate 
 
XX (XX.X) / XX 
 
Severe 
 
XX (XX.X) / XX 
 
 
 
 
System Organ Class 1 
Mild 
 
XX (XX.X) / XX 
 
Moderate 
 
XX (XX.X) / XX 
 
Severe 
 
XX (XX.X) / XX 
 
 
 
 
  Preferred Term 1 
Mild 
 
XX (XX.X) / XX 
 
Moderate 
 
XX (XX.X) / XX 
 
Severe 
 
XX (XX.X) / XX 
 
 
 
 
  Preferred Term 2 
Mild 
 
XX (XX.X) / XX 
 
Moderate 
 
XX (XX.X) / XX 
 
Severe 
 
XX (XX.X) / XX 
 
 
 
 
  ... 
... 
 
... 
 
 
 
 
System Organ Class 2 
Mild 
 
XX (XX.X) / XX 
 
Moderate 
 
XX (XX.X) / XX 
 
Severe 
 
XX (XX.X) / XX 
 
 
 
 
  ... 
... 
 
... 
 
AE=Adverse Event; MedDRA=Medical Dictionary for Regulatory Activities; TEAE=Treatment-Emergent Adverse Event. 
N: the number of subjects in the Safety population. 
n: the number of subjects with at least one TEAE within a specific category. Percentages are calculated as (100 x n/N). 
E: total number of TEAEs reported with appropriate severity. 
For ‘Overall’ and for each SOC and SOC/PT, each subject is counted once in the category of the maximum severity. 
For ‘Overall’, the number of all reported TEAEs are presented; for each SOC and SOC/PT, the number of TEAEs of maximum severity is given. 
If the severity is missing for a TEAE, then ‘Severe’ category is assigned. 
AEs are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 


 
SF_STAT001_ver 2_Eng 
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MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
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Programming note:  
System organ classes (SOC) and preferred terms (PT) within each SOC should be sorted in descending order of n (%). 
 
 
Similar to table 14.3.1.6.1, the following tables will be constructed: 
 
 
Table 14.3.1.6.2 Incidence of Treatment-emergent Adverse Events up to Week 4 by Maximum Severity  
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
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MC2 Therapeutics 
MC2-01-C6 
Table 14.3.1.7.1 Incidence of Treatment-Emergent Adverse Events by Closest Relationship 
Safety population 
Page Х of Х 
 
System Organ Class (SOC) 
  Preferred Term (PT) 
Relationship 
 
Total 
(N = XX) 
n (%) / E 
Overall 
Not related  
 
XX (XX.X) / XX 
 
Possibly related 
 
XX (XX.X) / XX 
 
Probably related 
 
XX (XX.X) / XX 
 
Definitely related 
 
XX (XX.X) / XX 
 
 
 
 
System Organ Class 1 
Not related  
 
XX (XX.X) / XX 
 
Possibly related 
 
XX (XX.X) / XX 
 
Probably related 
 
XX (XX.X) / XX 
 
Definitely related 
 
XX (XX.X) / XX 
 
 
 
 
  Preferred Term 1 
Not related  
 
XX (XX.X) / XX 
 
Possibly related 
 
XX (XX.X) / XX 
 
Probably related 
 
XX (XX.X) / XX 
 
Definitely related 
 
XX (XX.X) / XX 
 
 
 
 
  Preferred Term 2 
Not related  
 
XX (XX.X) / XX 
 
Possibly related 
 
XX (XX.X) / XX 
 
Probably related 
 
XX (XX.X) / XX 
 
Definitely related 
 
XX (XX.X) / XX 
 
 
 
 
  ... 
... 
 
... 
 
 
 
 
System Organ Class 2 
Not related  
 
XX (XX.X) / XX 
 
Possibly related 
 
XX (XX.X) / XX 
 
Probably related 
 
XX (XX.X) / XX 
 
Definitely related 
 
XX (XX.X) / XX 
 
 
 
 
  ... 
... 
 
... 
 
AE=Adverse Event; MedDRA=Medical Dictionary for Regulatory Activities; TEAE=Treatment-Emergent Adverse Event. 
N: the number of subjects in the Safety population. 
n: the number of subjects with at least one TEAE within a specific category. Percentages are calculated as (100 x n/N). 
E: total number of TEAEs reported with given category of relationship to study drug. 
For ‘Overall’ and for each SOC and SOC/PT, each subject is counted once in the category of the closest relationship. 
For ‘Overall’, the number of all reported TEAEs are presented; for each SOC and SOC/PT, the number of TEAEs of closest relationship is given. 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
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If the relationship is missing for a TEAE, then ‘Definitely related’ category is assigned. 
AEs are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  
System organ classes (SOC) and preferred terms (PT) within each SOC should be sorted in descending order of n (%). 
 
 
 
Similar to table 14.3.1.7.1, the following tables will be constructed (with the corresponding corrections of underlined fragments in the note): 
 
 
Table 14.3.1.7.2 Incidence of Treatment-Emergent Adverse Events up to Week 4 by Closest Relationship 
 
 
Similar to table 14.3.1.2.1, the following tables will be constructed (with the corresponding corrections of underlined fragments in the note): 
 
Table 14.3.1.8.1 Incidence of Treatment-emergent Adverse Events Leading to Discontinuation of Study Drug  
Table 14.3.1.8.2 Incidence of Treatment-emergent Adverse Events Leading to Discontinuation of Study Drug up to Week 4 
Table 14.3.1.9.1 Incidence of Treatment-emergent Adverse Events Leading to Withdrawal 
Table 14.3.1.9.2 Incidence of Treatment-emergent Adverse Events Leading to Withdrawal up to Week 4 
Table 14.3.1.10.1 Incidence of Non-serious treatment-emergent Adverse Events Occurred at a Frequency of >=5% 
Table 14.3.1.10.2 Incidence of Non-serious treatment-emergent Adverse Events Occurred at a Frequency of >=5% up to Week 4 
Table 14.3.1.11 Incidence of Treatment-emergent Adverse Events Related to Cosyntropin  
Table 14.3.1.12 Incidence of Treatment-emergent Adverse Events Related to Study Procedures 
Table 14.3.2.1 Incidence of Treatment-emergent Adverse Events Leading to Death  
Table 14.3.2.2 Incidence of Treatment-emergent Adverse Events Related to the Study Drug and Leading to Death  
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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HPA Axis Suppression 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.1.1 Summary of ACTH Challenge Test 
HPA population 
Page Х of Х 
 
Serum Cortisol (nmol/L) 
Total  
(N=XX) 
Pre-stimulation 
Post-stimulation 
 
 
 
Baseline 
 
 
    n 
XX 
XX 
    Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
XX.XX [XX.XX - XX.XX] 
    SD 
XX.XX 
XX.XX 
    Median 
XX.XX 
XX.XX 
    Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
    Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Visit 3 / Week 4 
 
 
    n 
XX 
XX 
    Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
XX.XX [XX.XX - XX.XX] 
    SD 
XX.XX 
XX.XX 
    Median 
XX.XX 
XX.XX 
    Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
    Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Visit 5 / Week 8 
 
 
    n 
XX 
XX 
    Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
XX.XX [XX.XX - XX.XX] 
    SD 
XX.XX 
XX.XX 
    Median 
XX.XX 
XX.XX 
    Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
    Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Follow-up 
 
 
    n 
XX 
XX 
    Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
XX.XX [XX.XX - XX.XX] 
    SD 
XX.XX 
XX.XX 
    Median 
XX.XX 
XX.XX 
    Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
    Min, Max 
XX.X, XX.X 
XX.X, XX.X 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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HPA=Hypothalamic-pituitary-adrenal. 
N: the number of subjects in the HPA population. n: the number of valid measurements.  
Measurements of serum cortisol levels pre- and post- stimulation with cosyntropin 0.25 mg are presented. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.1.2 Incidence of HPA Axis Suppression 
HPA population 
Page Х of Х 
 
 
 
 
Total 
(N = XX) 
 
 
 
 
HPA axis suppression 
 
 
 
 
 
 
 
Overall 
 
n’ (%) [1] 
 XX (XX.X)  
 
 
n (%) [2] 
XX (XX.X) 
 
 
95% CI 
XX.X, XX.X 
 
 
 
 
Visit 3 / Week 4  
 
n’ (%) [1] 
 XX (XX.X)  
     
 
n (%) [2] 
XX (XX.X) 
 
 
95% CI 
XX.X, XX.X 
 
 
 
 
Visit 5 / Week 8 
n’ (%) [1] 
 
XX (XX.X) 
     
 
n (%) [2] 
XX (XX.X) 
 
 
95% CI 
XX.X, XX.X 
 
 
 
 
 
HPA axis suppressed at Week 4 
n’ (%) [3] 
 XX (XX.X)  
 
 
n (%) [2] 
XX (XX.X) 
 
 
95% CI 
XX.X, XX.X 
 
 
 
 
 
HPA axis not suppressed at Week 4 
n’ (%) [3] 
 XX (XX.X)  
 
 
n (%) [2] 
XX (XX.X) 
 
 
95% CI 
XX.X, XX.X 
 
 
 
 
 
 
 
 
 
CI=Confidence Interval; HPA=Hypothalamic-pituitary-adrenal. 
N: the number of subjects in the HPA population. n: the number of subjects within a specific category. n’: the number of valid observations.  
[1] Subjects having any post-baseline values (for ‘Overall’ category) or values at the corresponding visit. Percentage is calculated as (100 x n/N).  
[2] Percentages are based on the corresponding number of valid observations. 
[3] Subjects with corresponding HPA suppression status at Week 4 having values at Visit 5 / Week 8. Percentage is calculated based on number of 
subjects with corresponding HPA suppression status at Week 4. 
Confidence interval is calculated using Clopper-Pearson method. 
Adrenal suppression is defined as the 30-minute post-stimulation serum cortisol level below 18 ug/dL (500 nmol/L). 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Calcium Metabolism 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.2.1 Summary of Calcium Metabolism Evaluation 
Safety population 
Page Х of Х 
       Parameter: Serum Calcium Corrected for Albumin (mmol/L) 
 
Total 
(N = XX) 
Change from the baseline  
 
 
 
Baseline 
 
 
  n 
XX 
 
  Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
 
  SD 
XX.XX 
 
  Median 
XX.XX 
 
  Q1, Q3 
XX.XX, XX.XX 
 
  Min, Max 
XX.X, XX.X 
 
 
 
 
Visit 3 / Week 4 
 
 
  n 
XX 
XX 
  Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
XX.XX [XX.XX - XX.XX] 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Visit 5 / Week 8 
 
 
  n 
XX 
XX 
  Mean [95% CI] 
XX.XX [XX.XX - XX.XX] 
XX.XX [XX.XX - XX.XX] 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
 
N: the number of subjects in the Safety population. n: the number of valid measurements.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  


 
SF_STAT001_ver 2_Eng 
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Report the following parameters: Serum Calcium (mmol/L), Urinary Calcium/Creatinine (mmol/mmol). 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Clinical Laboratory Evaluation 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.3.1 Summary of Hematology Parameters 
Safety population 
Page Х of Х 
 
       Parameter: XXXXXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
Change from the baseline  
 
 
 
Baseline 
 
 
  n 
XX 
 
  Mean 
XX.XX 
 
  SD 
XX.XX 
 
  Median 
XX.XX 
 
  Q1, Q3 
XX.XX, XX.XX 
 
  Min, Max 
XX.X, XX.X 
 
 
 
 
Visit 3 / Week 4 
 
 
  n 
XX 
XX 
  Mean 
XX.XX 
XX.XX 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Visit 5 / Week 8 
 
 
  n 
XX 
XX 
  Mean 
XX.XX 
XX.XX 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Highest post-baseline 
 
 
  n 
XX 
XX 
  Mean 
XX.XX 
XX.XX 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Lowest post-baseline 
 
 
  n 
XX 
XX 
  Mean 
XX.XX 
XX.XX 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
     
 
 
 
N: the number of subjects in the Safety population. 
n: the number of valid measurements. 
 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note: 
Report the following parameters: Hemoglobin (mmol/L), Hematocrit (L/L), Erythrocytes (10^12/L), MCV (fL), Leukocytes (10^9/L), Lymphocytes 
(10^9/L),  Lymphocytes/Leukocytes (%),  Monocytes (10^9/L),  Monocytes/Leukocytes (%),  Neutrophils (10^9/L),  Neutrophils/Leukocytes (%),  
Basophils (10^9/L),  Basophils/Leukocytes (%),  Eosinophils (10^9/L),  Eosinophils/Leukocytes (%),  Platelets (10^9/L).  
 
Similar to table 14.3.4.3.1, the following tables will be constructed: 
 
Table 14.3.4.3.2 Summary of Blood Chemistry Parameters 
 
Report the following parameters: Urea (mmol/L), Urea Nitrogen (mmol/L), Serum Glucose (mmol/L), Serum Creatinine (umol/L), Serum Albumin 
(g/L), Sodium (mmol/L), Potassium (mmol/L), Chloride (mmol/L), Serum Phosphate (mmol/L), Alkaline Phosphatase (U/L), Parathyroid Hormone 
(pmol/L). 
 
Table 14.3.4.3.3 Summary of Morning Urine Assessment Parameters 
 
Report the following parameters: Urinary Calcium (mmol/L), Total Calcium Excretion (mmol), Urinary Phosphate (mmol/L), Total Phosphate 
Excretion (mmol), Urinary Creatinine (g/L), Total Creatinine Excretion (g), Urinary Phosphate/Creatinine (mg/g), Volume (mL).  


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.4.1 Hematology Shifts from Baseline 
Safety population 
Page Х of Х 
 
Parameter: XXXXXXXXXXXXXXXXX (units) 
 
 
_____________________________________________Baseline_____________________________________________ 
 
Low 
Normal 
High 
Total 
 
 
 
 
 
 
Visit 3 / Week 4 
 
 
 
 
 
    Low 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Normal 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    High 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
Visit 5 / Week 8 
 
 
 
 
 
    Low 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Normal 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    High 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
Highest post-baseline 
 
 
 
 
 
    Low 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Normal 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    High 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
Lowest post-baseline 
 
 
 
 
 
    Low 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Normal 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    High 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
Percentages are based on the number of subjects with non-missing assessment at the corresponding time point and at baseline. 
For highest/lowest post-baseline values percentages are based on the number of subjects with non-missing assessment at baseline and at least one non-
missing post-baseline assessment for the corresponding parameter. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Page 75 out of 143 
 
 
Similar to table 14.4.2.2.1, the following tables will be constructed: 
 
Table 14.3.4.4.2 Blood Chemistry Shifts from Baseline 
Table 14.3.4.4.3 Morning Urine Assessment Shifts from Baseline 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Page 76 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.5.1 Incidence of Hematology Assessments Outside of Normal Range  
Safety population 
Page Х of Х 
       Parameter: XXXXXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
n (%) 
 
 
Overall 
 
    n [1] 
XX 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
Baseline 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
  Visit 3 / Week 4 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
  Visit 5 / Week 8 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
 
N: the number of subjects in the Safety population.  
n: the number of subjects within a specific category or number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
[1] Number of subjects with at least one non-missing post-baseline assessment of the corresponding parameter. 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Page 77 out of 143 
 
Similar to table 14.4.2.2.1, the following tables will be constructed: 
 
Table 14.3.4.5.2 Incidence of Blood Chemistry Assessments Outside of Normal Range 
Table 14.3.4.5.3 Incidence of Morning Urine Assessments Outside of Normal Range 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Page 78 out of 143 
 
Local Skin Reactions Assessment 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.6.1 Summary of Local Skin Reactions Assessment 
Safety population 
Page Х of Х 
 
       Parameter: XXXXXXXXXXXXXXXXXXXXXXXXXX 
Visit 
  Investigator Assessment 
Total 
(N = XX) 
n (%) 
 
 
Baseline 
 
  n 
XX 
  0 (Absent) 
XX (XX.X) 
  1 (Mild) 
XX (XX.X) 
  2 (Moderate) 
XX (XX.X) 
  3 (Severe) 
XX (XX.X) 
 
 
Visit 2 / Week 2 
 
  n 
XX 
  0 (Absent) 
XX (XX.X) 
  1 (Mild) 
XX (XX.X) 
  2 (Moderate) 
XX (XX.X) 
  3 (Severe) 
XX (XX.X) 
 
 
Visit 3 / Week 4 
 
  n 
XX 
  0 (Absent) 
XX (XX.X) 
  1 (Mild) 
XX (XX.X) 
  2 (Moderate) 
XX (XX.X) 
  3 (Severe) 
XX (XX.X) 
 
 
... 
 
  ... 
  ... 
 
 
 
 
 
N: the number of subjects in the Safety population. 
n: the number of subjects within a specific category or the number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 79 out of 143 
 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings  
 
Programming note: 
Report the following parameters: Investigator assessment of Erosion/ulceration in lesional area, Vesicles in lesional area, Erythema in perilesional area, 
Scaling in the perilesional area, Edema in perilesional area, Atrophy in perilesional area, Vesicles in perilesional area, Erosion/ulceration in 
perilesional area, Subject assessment of Burning or pain after application.  
Report the following visits: Baseline, Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8, Most severe post-baseline. 
 
Programming note: 
For parameter “Subject assessment of Burning or pain after application” report Visit 1/ Day 0 instead of Baseline assessment. 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Page 80 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.6.2 Local Skin Reactions Assessment Shifts from Baseline 
Safety population 
Page Х of Х 
 
Parameter: XXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
Baseline 
 
 
 
0 (Absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Total 
 
n (%) 
n (%) 
n (%) 
n (%) 
n (%) 
 
 
 
 
 
 
  Visit 2 / Week 2 
 
 
 
 
 
    0 (Absent) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    1 (Mild) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    2 (Moderate) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    3 (Severe) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
  Visit 3 / Week 4 
 
 
 
 
 
    ... 
... 
... 
... 
... 
... 
 
 
 
 
 
 
  ... 
 
 
 
 
 
    ... 
 
 
 
 
 
 
N: the number of subjects in the Safety population. 
n: the number of subjects within a specific category. Percentages are based on the number of non-missing values at baseline and at the corresponding 
visit. 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
Percentages are based on the number of subjects with non-missing assessment at the corresponding time point and at baseline. 
For the most severe post-baseline values percentages are based on the number of subjects with non-missing assessment at baseline and at least one non-
missing post-baseline assessment for the corresponding parameter. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note: 
Report the following parameters: : Investigator assessment of Erosion/ulceration in lesional area, Vesicles in lesional area, Erythema in perilesional 
area, Scaling in the perilesional area, Edema in perilesional area, Atrophy in perilesional area, Vesicles in perilesional area, Erosion/ulceration in 
perilesional area.  
Report the following visits: Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8, Most severe post-baseline. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Page 81 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.6.3 Summary of LSR Sum Score 
Safety population 
Page Х of Х 
 
 
Total 
(N = XX) 
Change from the baseline  
 
 
 
Baseline 
 
 
  n 
XX 
 
  Mean 
XX.X 
 
  SD 
XX.X 
 
  Median 
XX.X 
 
  Q1, Q3 
XX.X, XX.X 
 
  Min, Max 
XX, XX 
 
 
 
 
Visit 2 / Week 2 
 
 
  n 
XX 
XX 
  Mean 
XX.X 
XX.X 
  SD 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
  Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
  Min, Max 
XX, XX 
XX, XX 
 
 
 
Visit 3 / Week 4 
 
 
  n 
XX 
XX 
  Mean 
XX.X 
XX.X 
  SD 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
  Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
  Min, Max 
XX, XX 
XX, XX 
 
 
 
... 
 
 
  ... 
 
 
     
 
 
 
LSR=Local Skin Reactions. 
N: the number of subjects in the Safety population. 
n: the number of valid measurements. 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 82 out of 143 
 
 
Report the following visits: Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8. 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Page 83 out of 143 
 
Vital signs 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.7.1 Summary of Vital Signs 
Safety population 
Page Х of Х 
       Parameter: XXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
Change from the baseline  
 
 
 
  Baseline 
 
 
    n 
XX 
 
    Mean 
XX.X 
 
    SD 
XX.X 
 
    Median 
XX.X 
 
    Q1, Q3 
XX.X, XX.X 
 
    Min, Max 
XX, XX 
 
 
 
 
  Visit 2 / Week 2 
 
 
    n 
XX 
XX 
    Mean 
XX.X 
XX.X 
    SD 
XX.X 
XX.X 
    Median 
XX.X 
XX.X 
    Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
    Min, Max 
XX, XX 
XX, XX 
 
 
 
  ... 
 
 
    ... 
... 
... 
 
 
 
 
N: the number of subjects in the Safety population. 
n: the number of valid measurements. 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 84 out of 143 
 
Report the following parameters: Systolic blood pressure (mm Hg)/ Diastolic blood pressure (mm Hg)/ Pulse rate (beats/minute)/ Oral temperature (C), 
Tympanic temperature (C).  
 
Report the following visits: Baseline, Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8, Highest post-baseline, Lowest post-
baseline. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 85 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.7.2 Incidence of Vital Signs Assessments Outside of Normal Range 
Safety population 
Page Х of Х 
Parameter: XXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
n (%) 
 
 
Any Time After the Start of Treatment 
 
    n [1] 
XX 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
  Baseline 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
  Visit 2 / Week 2 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Out of Range 
XX (XX.X) 
      Low 
XX (XX.X) 
      High 
XX (XX.X) 
 
 
  ... 
 
    ... 
... 
 
 
 
N: the number of subjects in the Safety population.  
n: the number of subjects within a specific category or number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
[1] Number of subjects with at least one non-missing post-baseline assessment of the corresponding parameter. 
  
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 86 out of 143 
 
Report the following parameters: Systolic blood pressure (mm Hg)/ Diastolic blood pressure (mm Hg)/ Pulse rate (beats/minute)/ Oral temperature (C), 
Tympanic temperature (C).  
 
Report the following visits: Any Time After the Start of Treatment, Baseline, Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 87 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.7.3 Incidence of Notably Abnormal Vital Signs Assessments 
Safety population 
Page Х of Х 
Parameter: XXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
n (%) 
 
 
Any Time After the Start of Treatment 
 
  n [1] 
XX 
  Low (90 mmHg or lower and decreased by 20 mmHg or more) 
XX (XX.X) 
  High (180 mmHg or greater and increased by 20 mmHg or more) 
XX (XX.X) 
     
 
Baseline 
 
  n 
XX 
  Low (90 mmHg or lower) 
XX (XX.X) 
  High (180 mmHg or greater) 
XX (XX.X) 
 
 
Visit 2 / Week 2 
 
  n 
XX 
  Low (90 mmHg or lower and decreased by 20 mmHg or more) 
XX (XX.X) 
  High (180 mmHg or greater and increased by 20 mmHg or more) 
XX (XX.X) 
 
 
  ... 
 
    ... 
... 
 
 
 
N: the number of subjects in the Safety population.  
n: the number of subjects within a specific category or number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
[1] Number of subjects with at least one non-missing post-baseline assessment of the corresponding parameter. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  
Report the following parameters: Systolic blood pressure (mm Hg)/ Diastolic blood pressure (mm Hg)/ Pulse rate (beats/minute).  
Criteria for notable vital signs measurements are specified in SAP Section 9.5. 
 
Report the following visits: Any Time After the Start of Treatment, Baseline, Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8. 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Page 88 out of 143 
 
Physical Examination 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.8 Summary of Physical Parameters 
Safety population 
Page Х of Х 
       Parameter: Weight (kg) 
 
Total 
(N = XX) 
Change from the baseline  
 
 
 
  Baseline 
 
 
    n 
XX 
 
    Mean 
XX.X 
 
    SD 
XX.X 
 
    Median 
XX.X 
 
    Q1, Q3 
XX.X, XX.X 
 
    Min, Max 
XX, XX 
 
 
 
 
  Visit 3 / Week 4 
 
 
    n 
XX 
XX 
    Mean 
XX.X 
XX.X 
    SD 
XX.X 
XX.X 
    Median 
XX.X 
XX.X 
    Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
    Min, Max 
XX, XX 
XX, XX 
 
 
 
  ... 
 
 
    ... 
... 
... 
 
N: the number of subjects in the Safety population. 
n: the number of valid measurements. 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  
Report the following parameters: Weight (kg)/ Height (cm)/ BMI (kg/m2).  
Report the following visits: Baseline, Visit 3 / Week 4, Visit 5 / Week 8. 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 89 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.9 Summary of Physical Examination 
Safety population 
Page Х of Х 
Abbreviated physical examination 
 
Total 
(N = XX) 
n (%) 
 
 
Baseline 
 
  n 
XX 
  Normal 
XX (XX.X) 
  Abnormal NCS 
XX (XX.X) 
  Abnormal CS 
XX (XX.X) 
 
 
Visit 3 / Week 4 
 
  n 
XX 
  Normal 
XX (XX.X) 
  Abnormal NCS 
XX (XX.X) 
  Abnormal CS 
XX (XX.X) 
 
 
  ... 
 
    ... 
... 
 
 
 
CS=Clinically Significant; NCS=Not clinically significant. 
N: the number of subjects in the Safety population.  
n: the number of subjects within a specific category or number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
Programming note:  
Repeat for Complete dermatological examination.  
 
Report the following visits: Baseline, Visit 3 / Week 4, Visit 5 / Week 8, Follow-up. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 90 out of 143 
 
ECG 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.10.1 Summary of Electrocardiogram 
Safety population 
Page Х of Х 
       Parameter: XXXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
Change from 
the baseline  
 
 
 
  Baseline 
 
 
    n 
XX 
 
    Mean 
XX.X 
 
    SD 
XX.X 
 
    Median 
XX.X 
 
    Q1, Q3 
XX.X, XX.X 
 
    Min, Max 
XX, XX 
 
 
 
 
  Visit 3 / Week 4 
 
 
    n 
XX 
XX 
    Mean 
XX.X 
XX.X 
    SD 
XX.X 
XX.X 
    Median 
XX.X 
XX.X 
    Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
    Min, Max 
XX, XX 
XX, XX 
 
 
 
  Visit 5 / Week 8 
 
 
    n 
XX 
XX 
    Mean 
XX.X 
XX.X 
    SD 
XX.X 
XX.X 
    Median 
XX.X 
XX.X 
    Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
    Min, Max 
XX, XX 
XX, XX 
 
 
 
  ... 
 
 
    ... 
... 
... 
   
... 
... 
 
QTC-F=QT interval corrected according to Fridericia's formula; QTC-B=QT interval corrected according to Bazett's formula. 
N: the number of subjects in the Safety population. 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Page 91 out of 143 
 
n: the number of valid measurements. 
 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
Programming note:  
Report the following parameters: Heart rate (beats/min)/ RR interval (msec)/ PR interval (msec)/ QRS duration (msec), QT interval (msec), QTC-F 
interval (msec), QTC-B interval (msec).  
 
Report the following visits: Baseline, Visit 3 / Week 4, Visit 5 / Week 8, Highest post-baseline, Lowest post-baseline. 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 92 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.10.2 Incidence of Abnormal ECG Assessments 
Safety population 
Page Х of Х 
       Parameter: General Assessment 
 
Total 
(N = XX) 
n (%) 
 
 
Any Time After the Start of Treatment 
 
    n [1] 
XX 
    Abnormal 
XX (XX.X) 
    Abnormal CS 
XX (XX.X) 
 
 
  Baseline 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Abnormal NCS 
XX (XX.X) 
    Abnormal CS 
XX (XX.X) 
 
 
  Visit 3 / Week 4 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Abnormal NCS 
XX (XX.X) 
    Abnormal CS 
XX (XX.X) 
 
 
  Visit 5 / Week 8 
 
    n 
XX 
    Normal 
XX (XX.X) 
    Abnormal NCS 
XX (XX.X) 
    Abnormal CS 
XX (XX.X) 
 
 
    … 
… 
 
 
 
N: the number of subjects in the Safety population. n: the number of subjects within a specific category or number of valid observations. Percentages 
are based on the corresponding number of valid observations. 
[1] Number of subjects with at least one non-missing post-baseline assessment of the corresponding parameter. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 93 out of 143 
 
Programming note:  
Report the following visits: Any Time After the Start of Treatment, Baseline, Visit 3 / Week 4, Visit 5 / Week 8. 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 94 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.3.4.10.3 Incidence of Notably Abnormal ECG Assessments 
Safety population 
Page Х of Х 
Parameter: XXXXXXXXXXXXXX (units) 
 
Total 
(N = XX) 
n (%) 
 
 
Any Time After the Start of Treatment 
 
  n [1] 
XX 
  QTc interval > 450 
XX (XX.X) 
  QTc interval > 480 
XX (XX.X) 
  QTc interval > 500 
XX (XX.X) 
  QTc interval increases from baseline >30 
XX (XX.X) 
  QTc interval increases from baseline >60 
XX (XX.X) 
     
 
Baseline 
 
  n 
XX 
  QTc interval > 450 
XX (XX.X) 
  QTc interval > 480 
XX (XX.X) 
  QTc interval > 500 
XX (XX.X) 
 
 
Visit 3 / Week 4 
 
  n 
XX 
  QTc interval > 450 
XX (XX.X) 
  QTc interval > 480 
XX (XX.X) 
  QTc interval > 500 
XX (XX.X) 
  QTc interval increases from baseline >30 
XX (XX.X) 
  QTc interval increases from baseline >60 
XX (XX.X) 
 
 
... 
 
  ... 
... 
 
 
 
N: the number of subjects in the Safety population.  
n: the number of subjects within a specific category or number of valid observations. Percentages are based on the corresponding number of valid 
observations. 
[1] Number of subjects with at least one non-missing post-baseline assessment of the corresponding parameter. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 95 out of 143 
 
Programming note:  
Report the following parameters: QTC-F interval (msec), QTC-B interval (msec).  
Report the following visits: Any Time After the Start of Treatment, Baseline, Visit 3 / Week 4, Visit 5 / Week 8. 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 96 out of 143 
 
Physician Global Assessment of Psoriasis Severity 
MC2 Therapeutics 
MC2-01-C6 
Table 14.4.1.1 Summary of PGA 
Safety population 
Page Х of Х 
 
Visit 
Total 
(N = XX) 
 
Change from baseline 
 
 
 
Baseline 
 
 
  n 
XX 
 
  Mean 
XX.X 
 
  SD 
XX.X 
 
  Median 
XX.X 
 
  Q1, Q3 
XX.X, XX.X 
 
  Min, Max 
XX, XX 
 
 
 
 
Visit 2 / Week 2 
 
 
  n 
XX 
XX 
  Mean 
XX.X 
XX.X 
  SD 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
  Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
  Min, Max 
XX, XX 
XX, XX 
 
 
 
Visit 3 / Week 4 
 
 
  n 
XX 
XX 
  Mean 
XX.X 
XX.X 
  SD 
XX.X 
XX.X 
  Median 
XX.X 
XX.X 
  Q1, Q3 
XX.X, XX.X 
XX.X, XX.X 
  Min, Max 
XX, XX 
XX, XX 
 
 
 
... 
 
 
  ... 
 
 
 
 
 
 
 
 
 
PGA=Physician global assessment. 
N: the number of subjects in the Safety population. 
n: the number of valid observations.  


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
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Page 97 out of 143 
 
Baseline is the last non-missing assessment prior to the first dose of the study drug. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings  
 
Programming note: 
Report the following visits: Baseline, Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8. 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 98 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.4.1.2 Summary of Treatment Success 
Safety population 
Page Х of Х 
 
 
 
Total 
(N = XX) 
 
 
 
Treatment success 
 
 
 
 
 
Overall 
n’ (%) [1] 
 XX (XX.X)  
 
n (%) [2] 
XX (XX.X) 
 
95% CI 
XX.X, XX.X 
 
 
 
Visit 2 / Week 2  
n’ (%) [1]  
 XX (XX.X)  
     
n (%) [2] 
XX (XX.X) 
 
95% CI 
XX.X, XX.X 
 
 
 
Visit 3 / Week 4  
n’ (%) [1]  
 XX (XX.X)  
     
n (%) [2] 
XX (XX.X) 
 
95% CI 
XX.X, XX.X 
 
 
 
... 
... 
... 
 
 
 
 
PGA=Physician global assessment. 
N: the number of subjects in the Safety population. n: the number of subjects within a specific category. n’: the number of valid observations.  
[1] Subjects having any post-baseline values (for ‘Overall’ category) or values at the corresponding visit. Percentage is calculated as (100 x n/N).  
[2] Percentages are based on the corresponding number of valid observations. 
Confidence interval is calculated using Clopper-Pearson method. 
Treatment success is defined as at least 2-point decrease from Baseline in the PGA on the trunk, limbs, and scalp. 
Baseline is the last non-missing assessment prior to the first dose of the study drug. Only subjects having at least moderate severity at baseline will 
be included into the summary. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings  
 
Programming note: 
Report the following visits: Overall, Visit 2 / Week 2, Visit 3 / Week 4, Visit 4 / Week 6, Visit 5 / Week 8. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
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Page 99 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.4.1.3 PGA Shifts from Baseline 
Safety population 
Page Х of Х 
 
 
 
_____________________________________________Baseline_____________________________________________ 
 
0 - Clear 
1 – Almost Clear 
2 - Mild 
    3 - Moderate 
4 - Severe 
Total 
 
 
 
 
 
 
 
 
Visit 2 / Week 2 
 
 
 
 
 
 
 
    0 - Clear 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    1 – Almost Clear 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    2 - Mild 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    3 - Moderate 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    4 - Severe 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
 
 
Visit 3 / Week 4 
 
 
 
 
 
 
 
    0 - Clear 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    1 – Almost Clear 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    2 - Mild 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    3 - Moderate 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    4 - Severe 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
    Total 
n (%) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (100) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PGA=Physician global assessment. 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
Percentages are based on the number of subjects with non-missing assessment at the corresponding time point and at baseline. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 100 out of 143 
 
Body Surface Area Involvement Assessment 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.4.2.1 Summary of Body Surface Area Involvement 
Safety population 
Page Х of Х 
 
       Parameter: XXXXXXXXXXXXXXXXX (%) 
 
Total 
(N = XX) 
Change from the baseline  
 
 
 
Baseline 
 
 
  n 
XX 
 
  Mean 
XX.XX 
 
  SD 
XX.XX 
 
  Median 
XX.XX 
 
  Q1, Q3 
XX.XX, XX.XX 
 
  Min, Max 
XX.X, XX.X 
 
 
 
 
Visit 3 / Week 4 
 
 
  n 
XX 
XX 
  Mean 
XX.XX 
XX.XX 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
Visit 5 / Week 8 
 
 
  n 
XX 
XX 
  Mean 
XX.XX 
XX.XX 
  SD 
XX.XX 
XX.XX 
  Median 
XX.XX 
XX.XX 
  Q1, Q3 
XX.XX, XX.XX 
XX.XX, XX.XX 
  Min, Max 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
     
 
 
 
BSA=Body Surface Area. 
N: the number of subjects in the Safety population. 
n: the number of valid measurements. 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 101 out of 143 
 
 
The baseline value for a variable is defined as the last non-missing value collected before the first study drug application.  
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
Programming note: 
Report the following parameters: Scalp BSA psoriatic involvement (%), Neck, Trunk and/or Limbs BSA psoriatic involvement (%), Total psoriatic 
involvement (%).  
Report the following visits: Baseline, Visit 3 / Week 4, Visit 5 / Week 8. 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 102 out of 143 
 
Psoriasis Treatment Convenience Scale 
 
MC2 Therapeutics 
MC2-01-C6 
Table 14.4.3.1 Summary of Psoriasis Treatment Convenience Scale 
Safety population 
Page Х of Х 
 
Parameter: XXXXXXXXXXXXXXXXX 
 
Total 
(N = XX) 
 
 
Visit 2 / Week 2 
 
  n 
XX 
  Mean 
XX.X 
  SD 
XX.X 
  Median 
XX.X 
  Q1, Q3 
XX.X, XX.X 
  Min, Max 
XX, XX 
 
 
Visit 3 / Week 4 
 
  n 
XX 
  Mean 
XX.X 
  SD 
XX.X 
  Median 
XX.X 
  Q1, Q3 
XX.X, XX.X 
  Min, Max 
XX, XX 
 
 
... 
 
  ... 
... 
     
 
 
PTCS=Psoriasis Treatment Convenience Scale.  
N: the number of subjects in the Safety population. 
n: the number of valid measurements. 
Each question is rated on a 1-10 scale from least to most favorable response. PTCS total score is the sum of the scores on questions 1 to 5.  
If more than two questions are not answered, the PTCS total score is missing. If one or two questions remain unanswered, the missing scores are 
replaced by the average of the answered scores for the summation. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 103 out of 143 
 
 
Programming note:  
Report the following parameters: PTCS Total Score, Q1. How easy was the treatment to apply to the skin?, Q2. How greasy was the treatment when 
applying it to the skin?, Q3. How moisturized did your skin feel after applying the treatment?, Q4. How greasy did your skin feel after applying the 
treatment?, Q5. How much did treating your skin disrupt your daily routine?, Q6. Overall, how satisfied were you with the medical treatment?.  
 
Report the following visits: Visit 2 / Week 2, Visit 3 / Week 4, Visit 5 / Week 8. 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 104 out of 143 
 
Figures Shells 
MC2 Therapeutics 
MC2-01-C6 
Figure 16.2.5.4 Individual BDP Plasma Concentration-time Profiles on Linear and Semi-logarithmic Scales Week 4 
PK population 
Subject=XXXX 
 
 
 
 
 
 
 
0
1
2
3
4
5
6
Time (h)
0
10
20
30
40
50
60
70
80
90
100
Concentration (pg/mL)


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 105 out of 143 
 
 
 
 
BDP=Betamethasone dipropionate; BLQ=Below Limit of Quantification; LLOQ=Lower Limit of Quantification. 
BLQ concentrations were substituted with LLOQ for the calculation for graphic presentation. LLOQ for BDP is XX.X pg/mL. 
 
Path to the program code, date and time of output/ Datasets used/ Referenced Data Listings 
 
 
 
Similar to figure 16.2.5.4, the following figures will be constructed (with modification of underlined fragments): 
 
 
Figure 16.2.5.5 Individual Calcipotriol (CAL) Plasma Concentration-time Profiles on Linear and Semi-logarithmic Scales Week 4 
Figure 16.2.5.6 individual MC1080 Plasma Concentration-time Profiles on Linear and Semi-logarithmic Scales Week 4 
Figure 16.2.5.7 individual Betamethasone 17-propionate, Plasma Concentration-time Profiles on Linear and Semi-logarithmic Scales Week 4 
0
1
2
3
4
5
6
Time (h)
1
10
100
Concentration (pg/mL)


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 106 out of 143 
 
Listings Shells 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.1.1 Analysis Populations 
All Enrolled subjects 
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
All 
Enrolled 
subjects 
Date of Informed 
Consent/Assent 
Allocated 
to 
treatment  
Safety 
Population 
HPA 
Population 
Reason for 
Exclusion 
from HPA 
population 
PK 
Population 
Reason for 
Exclusion 
from PK 
population 
XXX/XX/XXXXX 
14/F/A/NHL 
Yes 
YYYY-MM-DD/ XX/ 
YYYY-MM-DD/ XX 
No 
No 
No 
XXXXXXXXXX 
No 
XXXXXXXXXX 
XXX/XX/XXXXX 
15/M/W/HL 
Yes 
YYYY-MM-DD/ XX/ 
YYYY-MM-DD/ XX 
Yes 
Yes 
Yes 
 
No 
XXXXXXXXXX 
XXX/XX/XXXXX 
16/F/A/NHL 
Yes 
YYYY-MM-DD/ XX/ 
YYYY-MM-DD/ XX 
Yes 
Yes 
Yes 
 
Yes 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
HPA=Hypothalamic-pituitary-adrenal; PK=Pharmacokinetics. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 107 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.1.2 Subject Visits 
All Enrolled subjects 
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Date / Study day 
Main reason for unscheduled visit 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXXX 
YYYY-MM-DD/ XX 
 
XXX/XX/XXXXX 
15/M/W/HL 
XXXXXX 
YYYY-MM-DD/ XX 
 
XXX/XX/XXXXX 
16/F/A/NHL 
XXXXXX 
YYYY-MM-DD/ XX 
XXXXXXXXXXX XXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 108 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.1.3 Study Completion 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Date of Study Completion or 
Discontinuation/ Study Day 
End of Study  
Status 
Reason for Study Discontinuation 
XXX/XX/XXXXX 
14/F/A/NHL 
YYYY-MM-DD/ XX 
Discontinued 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXX/XX/XXXXX 
15/M/W/HL 
YYYY-MM-DD/ XX 
Discontinued 
Other: XXXXXXXXXXXXXXXXXXXXX 
XXX/XX/XXXXX 
16/F/A/NHL 
YYYY-MM-DD/ XX 
Completed 
 
XXX/XX/XXXXX 
16/M/A/NHL 
YYYY-MM-DD/ XX 
Screening failure 
Inconsistency with inclusion / exclusion criteria: XXXXX 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 109 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.1.4 Study Treatment Completion 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Date of Study Treatment 
Completion or 
Discontinuation/ Study Day 
Was the IP 
discontinued before 
Week 8 visit? 
Reason for Study Treatment Discontinuation 
XXX/XX/XXXXX 
14/F/A/NHL 
YYYY-MM-DD/ XX 
Yes 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
XXX/XX/XXXXX 
15/M/W/HL 
YYYY-MM-DD/ XX 
Yes 
Other: XXXXXXXXXXXXXXXXXXXXX 
XXX/XX/XXXXX 
16/F/A/NHL 
YYYY-MM-DD/ XX 
No 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 110 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.2.1 Violation of Inclusion/Exclusion Criteria 
All Enrolled subjects 
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Category 
Criterion number/Criterion 
Result 
XXX/XX/XXXXX 
14/F/A/NHL 
Inclusion criteria 
XX/XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX No 
 
 
Exclusion criteria 
XX/XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX Yes 
 
 
Exclusion criteria 
XX/XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX Yes 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 111 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.2.2 Protocol Deviations 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Date of 
Deviation 
Revealed 
Visit 
Deviation Category/  
Subcategory 
Issue 
Description of deviation 
Assessment 
XXX/XX/XXXXX 14/F/A/NHL 
YYYY-MM-DD 
XXXXX 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
Major 
XXX/XX/XXXXX 15/M/W/HL 
YYYY-MM-DD 
XXXXX 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
Minor 
XXX/XX/XXXXX 16/F/A/NHL 
YYYY-MM-DD 
XXXXX 
XXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
XXXXXXXXXXXXXXXXXXXXXXXXX 
Minor 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 112 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.4.1 Demographics and Other Baseline Characteristics 
All Enrolled subjects 
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Year of 
Birth 
Fitzpatrick Skin 
Type 
Date of 
Diagnosis 
Duration of 
Disease (months) 
Previous Treatments 
XXX/XX/XXXXX 
14/F/A/NHL 
YYYY 
XXXXXXXXXXXXXX 
YYYY-MM 
XX.X 
Systemic: Biologics and systemic/ TNF-a 
inhibitors/ Topical: vitamin D analogs 
XXX/XX/XXXXX 
15/M/W/HL 
YYYY 
XXXXXXXXXXXXXX 
YYYY-MM 
XX.X 
 
XXX/XX/XXXXX 
16/F/A/NHL 
YYYY 
XXXXXXXXXXXXXX 
YYYY-MM 
XX.X 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 113 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.4.2 Baseline Variables 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter (Unit) 
Visit 
Result 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXXXXXX (XXXXXX) 
Scr V1 
XX.X 
 
 
 
Scr V2 
XX.X 
 
 
 
V1 Day0 
XX.X 
 
 
 
Baseline 
XX.X 
 
 
XXXXXXXXX (XXXXXX) 
Scr V1 
XX.X 
 
 
 
Scr V2 
XX.X 
... 
 
 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 114 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.4.3 Medical History 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
System Organ Class/ 
Preferred Term/ 
Lowest Level Term/ 
Condition/Diagnosis 
Prior/Concurrent 
Start Date/ 
Study Day 
End Date /  
Study Day 
Ongoing at the End 
of Clinical Trial 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
PR 
YYYY-MM-DD/ 
XX 
YYYY-MM-DD/ XX 
Resolved 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
PR=Prior, C=Concomitant. 
Terms are coded by MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
Programming note: 
Sort by ascending start date within subject. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 115 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.4.4 Prior/Concomitant Therapy 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
3rd Lvl, Pharmacological Subgroup/ 
4th Lvl, Chemical Subgroup/ 
5th Lvl, Chemical Substance/ 
Medication 
Prior/ 
Concomitant 
Start Date/  
Study Day/ 
Stop Date/ 
Study Day 
Dose (Units)/ 
Frequency/ 
Route 
Formulation/ 
Location 
Indication 
XXX/XX/XXXXX 14/F/A/NHL 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
PR 
YYYY-MM-DD/ 
XX/  
YYYY-MM-DD/ 
XX 
XXXXX (XXXXX)/ 
XXXXX/ 
XXXXX 
XXXXX/ 
XXXXX 
XXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
C 
YYYY-MM-DD/ 
XX/  
Ongoing 
XXXXX (XXXXX)/ 
XXXXX/ 
XXXXX 
XXXXX/ 
XXXXX 
XXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
… 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
PR=Prior, C=Concomitant, PT=Post-Treatment. 
Drug and non-drug therapy records are coded using WHODD version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
Programming note: 
Sort by ascending start date within subject. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 116 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.4.5 Prior/Concomitant Procedures 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
System Organ Class/ 
Preferred Term/ 
Lowest Level Term/ 
Therapy/Procedure 
Start date, Time/  
Study day/ 
Stop date, Time/ 
Study day 
Location 
Indication 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
YYYY-MM-DD HH:MM/ XX/  
YYYY-MM-DD HH:MM/ XX 
XXXXXXXXXXXXXX 
XXXXXXXXXX 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
Procedures are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
Programming note: 
Sort by ascending start date within subject. 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 117 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.5.1 Exposure 
Safety population 
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Study Period 
Date of First 
Application/ 
Study Day 
Date of Last 
Application/ 
Study Day 
Total 
Duration of 
Exposure 
(days) 
Extent of 
Exposure 
(days) 
Number 
of 
Missed 
Doses 
Total Dose (g)/ 
Average Weekly 
Dose (g)  
Compliance 
(%) 
XXX/XX/XXXXX 14/F/A/NHL 
Overall 
YYYY-MM-DD/ 1 
YYYY-MM-DD/ XX 
XX 
XX 
XX 
XX.X/ XX.X 
XX.X 
 
 
Up to Week 2 
YYYY-MM-DD/ 1 
YYYY-MM-DD/ XX 
XX 
XX 
XX 
XX.X/ XX.X 
XX.X 
 
 
Up to Week 4 
YYYY-MM-DD/ 1 
YYYY-MM-DD/ XX 
XX 
XX 
XX 
XX.X/ XX.X 
XX.X 
 
 
From Week 4 
to Week 8 
YYYY-MM-DD/ 
XX 
YYYY-MM-DD/ XX 
XX 
XX 
XX 
XX.X/ XX.X 
XX.X 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
Lost and unused tubes were not accounted for in the calculation of total dose. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 118 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.5.2 Study Drug Compliance 
Safety population 
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Was the subject 
diary completed by 
the patient 
(Reason, if Not 
Completed)? 
Did the subject apply 
the study drug once 
daily to the scalp, 
trunk and/or limbs 
since the last visit? 
 
Is the PGA “clear” and was the 
subject recommended to stop the 
treatment with study drug at the 
visit? 
Was the treatment with study 
drug restarted by the subject 
after interruption at the last 
visit?/ 
Restart Date 
XXX/XX/XXXXX 14/F/A/NHL 
V2/Week2 XXX 
XXX 
 
 
 
 
V3/Week4 XXX 
XXX 
XXX 
 
 
 
V5/Week8 XXX 
XXX 
 
XXX/ YYYY-MM-DD 
 
 
... 
... 
... 
 
... 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 119 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.5.3 Missed Doses 
Safety population 
Page Х of Х 
 
Country/Site ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Date/ Study Day 
 
Reason Not Administered 
XXX/XX/XXXXX 
14/F/A/NHL 
YYYY-MM-DD/ XX 
Approved Discontinuation 
 
 
YYYY-MM-DD/ XX 
Missed 
 
 
YYYY-MM-DD/ XX 
Missed 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 120 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.5.4 Study Drug Accountability 
Allocated to treatment 
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Dispensed 
Kit Number 
Date Dispensed/ Study Day/ 
Date Returned/ Study Day 
Tube Assessment 
Returned 
Amount 
Used Between 
 
XXX/XX/XXXXX 
14/F/A/NHL 
V1 (Day 0) 
XXXXXXXXX 
YYYY-MM-DD/ XX/ 
YYYY-MM-DD/ XX/ 
 
SEAL BROKEN 
XX.X g 
XXXXXXXXXXXX/ 
XXXXXXXXXXXX 
 
 
 
XXXXXXXXX 
YYYY-MM-DD/ XX/ 
YYYY-MM-DD/ XX/ 
 
SEALED 
 
 
 
 
 
XXXXXXXXX 
YYYY-MM-DD/ XX/ 
YYYY-MM-DD/ XX/ 
 
SEAL BROKEN 
XX.X g 
XXXXXXXXXXXX/ 
XXXXXXXXXXXX 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 121 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.7.1 Adverse Events 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
AE 
No/ 
TEAE 
[1]/ 
SAE 
[2] 
System Organ Class/ 
Preferred Term/ 
Lowest Level Term/ 
Reported Term 
Start Date, Time/  
Study Day/  
End Date, Time/  
Study Day 
Severity/ 
Relationship 
to IP/ 
Action taken 
with IP/ 
Outcome 
 
Concomitant therapy?/  
Concomitant non-drug therapy?/ 
Concomitant procedures?/ 
Did subject withdraw due to this AE?/ 
Is AE related to Cosyntropin?/ 
Is AE related to a study procedure 
(specify)? 
Location of AE to Treatment Area 
XXX/XX/XXXXX 
14/F/A/NHL 
XX/ 
XXX/ 
XXX 
(X,X) 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
YYYY-MM-DD HH:MM/ 
XXX/ 
YYYY-MM-DD HH:MM/ 
XXX 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX 
XXX/ XXX/ XXX/ 
XXX/ XXX/ XXX (XXXXXXXX XXXXXXXXXX)/ 
XXXXXXXXXXXXXXX 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
AE = Adverse Event, SAE = Serious Adverse Event, TEAE = Treatment-Emergent Adverse Event; IP=Investigational Product. 
[1] TEAE is any reported adverse event that starts after initiation of the study therapy. 
[2] Seriousness criteria: 1 = <<Death>>, 2 = <<Life-threatening>>, 3 = << Requires in-patient hospitalization or prolongation of existing hospitalization>>, 
4 = << Results in persistent or significant disability/incapacity>>, 5 = << Congenital anomaly/birth defect>>, 6 = << Other serious or important medical 
event>>. 
AEs are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 
 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 122 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.7.2 Serious Adverse Events 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)
/ 
Sex/Race/ 
Ethnicity 
AE No/ 
TEAE 
[1]/ 
SAE 
[2] 
System Organ Class/ 
Preferred Term/ 
Lowest Level Term/ 
Reported Term 
Start Date, Time/  
Study Day/  
End Date, Time/  
Study Day 
Severity/ 
Relationship 
to IP/ 
Action taken 
with IP/ 
Outcome 
 
Concomitant therapy?/  
Concomitant non-drug therapy?/ 
Concomitant procedures?/ 
Did subject withdraw due to this AE?/ 
Is AE related to Cosyntropin?/ 
Is AE related to a study procedure 
(specify)?/ 
Location of AE to Treatment Area 
XXX/XX/XXXXX 
14/F/A/NHL 
XX/ 
XXX/ 
XXX 
(X,X) 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
YYYY-MM-DD HH:MM/ 
XXX/ 
YYYY-MM-DD HH:MM/ 
XXX 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX 
XXX/ XXX/ XXX/ 
XXX/ XXX/ XXX (XXXXXXXX XXXXXXXXXX)/ 
XXXXXXXXXXXXXXX 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
AE = Adverse Event, SAE = Serious Adverse Event, TEAE = Treatment-Emergent Adverse Event; IP=Investigational Product. 
[1] TEAE is any reported adverse event that starts after initiation of the study therapy. 
[2] Seriousness criteria: 1 = <<Death>>, 2 = <<Life-threatening>>, 3 = << Requires in-patient hospitalization or prolongation of existing hospitalization>>, 
4 = << Results in persistent or significant disability/incapacity>>, 5 = << Congenital anomaly/birth defect>>, 6 = << Other serious or important medical 
event>>. 
AEs are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 123 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.7.3 Listing of Adverse Events Leading Discontinuation of Study Drug 
Safety population 
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
AE 
No/ 
TEAE 
[1]/ 
SAE 
[2] 
System Organ Class/ 
Preferred Term/ 
Lowest Level Term/ 
Reported Term 
Start Date, Time/  
Study Day/  
End Date, Time/  
Study Day 
Severity/ 
Relationship 
to IP/ 
Action taken 
with IP/ 
Outcome 
 
Concomitant therapy?/  
Concomitant non-drug therapy?/ 
Concomitant procedures?/ 
Did subject withdraw due to this AE?/ 
Is AE related to Cosyntropin?/ 
Is AE related to a study procedure 
(specify)?/ 
Location of AE to Treatment Area 
XXX/XX/XXXXX 
14/F/A/NHL 
XX/ 
XXX/ 
XXX 
(X,X) 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
YYYY-MM-DD HH:MM/ 
XXX/ 
YYYY-MM-DD HH:MM/ 
XXX 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX 
XXX/ XXX/ XXX/ 
XXX/ XXX/ XXX (XXXXXXXX XXXXXXXXXX)/ 
XXXXXXXXXXXXXXX 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
AE = Adverse Event, SAE = Serious Adverse Event, TEAE = Treatment-Emergent Adverse Event; IP=Investigational Product. 
[1] TEAE is any reported adverse event that starts after initiation of the study therapy. 
[2] Seriousness criteria: 1 = <<Death>>, 2 = <<Life-threatening>>, 3 = << Requires in-patient hospitalization or prolongation of existing hospitalization>>, 
4 = << Results in persistent or significant disability/incapacity>>, 5 = << Congenital anomaly/birth defect>>, 6 = << Other serious or important medical 
event>>. 
AEs are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 124 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.7.4 Listing of Adverse Events Leading to Withdrawal 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
AE 
No/ 
TEAE 
[1]/ 
SAE 
[2] 
System Organ Class/ 
Preferred Term/ 
Lowest Level Term/ 
Reported Term 
Start Date, Time/  
Study Day/  
End Date, Time/  
Study Day 
Severity/ 
Relationship 
to IP/ 
Action taken 
with IP/ 
Outcome 
 
Concomitant therapy?/  
Concomitant non-drug therapy?/ 
Concomitant procedures?/ 
Did subject withdraw due to this AE?/ 
Is AE related to Cosyntropin?/ 
Is AE related to a study procedure 
(specify)?/ 
Location of AE to Treatment Area 
XXX/XX/XXXXX 
14/F/A/NHL 
XX/ 
XXX/ 
XXX 
(X,X) 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX/ 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
YYYY-MM-DD HH:MM/ 
XXX/ 
YYYY-MM-DD HH:MM/ 
XXX 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX/ 
XXXXXXXXXX 
XXX/ XXX/ XXX/ 
Yes/ XXX (XXXXXXXX XXXXXXXXXX)/ 
XXXXXXXXXXXXXXX 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
AE = Adverse Event, SAE = Serious Adverse Event, TEAE = Treatment-Emergent Adverse Event; IP=Investigational Product. 
[1] TEAE is any reported adverse event that starts after initiation of the study therapy. 
[2] Seriousness criteria: 1 = <<Death>>, 2 = <<Life-threatening>>, 3 = << Requires in-patient hospitalization or prolongation of existing hospitalization>>, 
4 = << Results in persistent or significant disability/incapacity>>, 5 = << Congenital anomaly/birth defect>>, 6 = << Other serious or important medical 
event>>. 
AEs are coded using MedDRA version XX.X. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 125 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.1 Hematology in SI Units 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter 
(Units) 
Visit 
Date/ Study Day 
Result 
Reference 
Range 
Change from 
Baseline 
 
Reason if Not 
Done/ Comment 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @L 
XX.X-XX.X 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
XX.X 
 
 
 
 
V5/Week8 
 
Not Done 
XX.X-XX.X 
 
XXXXXXX XXXXXXx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @ 
XX.X-XX.X 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X H 
XX.X-XX.X 
XX.X 
XXXXXXXXXXXXXXX 
 
 
 
V5/Week 
YYYY-MM-DD/ XX 
XX.X H 
XX.X-XX.X 
XX.X 
 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit.  
@ indicates baseline assessment. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 126 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.2 Serum Biochemistry in SI Units 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter 
(Units) 
Visit 
Date/ Study Day 
Result 
Reference Range 
Change from 
Baseline 
 
Reason if Not 
Done/ Comment 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @L 
XX.X-XX.X 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
XX.X 
 
 
 
 
V5/Week8 
 
Not Done 
XX.X-XX.X 
 
XXXXXXX XXXXXXx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @H 
XX.X-XX.X 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X H 
XX.X-XX.X 
XX.X 
XXXXXXXXXXXX 
 
 
 
V5/Week 
YYYY-MM-DD/ XX 
XX.X H 
XX.X-XX.X 
XX.X 
 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit.  
@ indicates baseline assessment. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 127 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.3 Morning Urine Assessment in SI Units 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter 
(Units) 
Visit 
Date/ Study Day 
Result 
Reference Range 
Change from 
Baseline 
 
Reason if Not 
Done/ Comment 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @L 
XX.X-XX.X 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
XX.X 
 
 
 
 
V4/Week6 
 
Not 
Done 
XX.X-XX.X 
 
XXXXXXX XXXXXXx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @ 
XX.X-XX.X 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
XX.X 
 
 
 
 
V4/Week6 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
XX.X 
 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit.  
@ indicates baseline assessment. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 128 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.4  24-hour Urine Assessment 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter 
(Units) 
Visit 
Date/ Study Day 
Result 
Reference Range 
Reason if Not 
Done/ Comment 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXX (XXX) 
XXXXXXXX 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
 
 
 
 
XXXXXXXX 
YYYY-MM-DD/ XX 
XX.X L 
XX.X-XX.X 
 
 
 
 
XXXXXXXX 
 
Not Done 
XX.X-XX.X 
XXXXXXX XXXXXXx 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
XXXXX (XXX) 
XXXXXXXX 
YYYY-MM-DD/ XX 
XX.X 
XX.X-XX.X 
 
 
 
 
XXXXXXXX 
YYYY-MM-DD/ XX 
XX.X H 
XX.X-XX.X 
 
 
 
 
XXXXXXXX 
YYYY-MM-DD/ XX 
XX.X 
XX.X-XX.X 
 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit.  
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 129 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.5 Serum Pregnancy Test 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter 
(Units) 
Visit 
Date of Sample/ Study Day 
Result 
Reasons if Not Done 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXX (XXX) 
Scr V2 
YYYY-MM-DD/ XX 
XX.X 
 
 
 
 
V3/Week4 
 
Not Done 
XXXXXX XXXXXXXXX XXXX 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
XX.X 
 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 130 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.6 Urine Pregnancy Test 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Result 
Reasons if Not Done 
XXX/XX/XXXXX 
14/F/A/NHL 
Scr V2 
Negative 
 
 
 
V3/Week4 
Not Done 
XXXXXX XXXXXXXXX XXXX 
 
 
V5/Week8 
Negative 
 
... 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 131 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.7 ACTH Challenge Test  
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Date, Time of 
assessment/  
Study Day 
Parameter (Units) 
HPA Axis 
Suppression 
Noted 
Result 
Reason if 
Not Done 
XXX/XX/XXXXX 
14/F/A/NHL 
Scr V2 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol pre-stimulation 
(nmol/L) 
 
XX.X 
 
 
 
 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol post-stimulation 
(nmol/L) 
No 
XX.X 
 
 
 
V3/Week 4 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol pre-stimulation 
(nmol/L) 
 
XX.X 
 
 
 
 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol post-stimulation 
(nmol/L) 
No 
XX.X 
 
 
 
V5/Week 8 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol pre-stimulation 
(nmol/L) 
 
XX.X 
 
 
 
 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol post-stimulation 
(nmol/L) 
No 
XX.X 
 
 
 
FU 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol pre-stimulation 
(nmol/L) 
 
XX.X 
 
 
 
 
YYYY-MM-DD 
HH:MM/ XX 
Serum cortisol post-stimulation 
(nmol/L) 
No 
XX.X 
 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 132 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.8.8 Clinically Significant Laboratory Abnormalities 
Safety population 
Page Х of Х 
 
Country/Site ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Panel 
Visit 
Date/ Study Day 
Comments 
XXX/XX/XXXXX 
14/F/A/NHL 
Hematology 
V3/Week4 
YYYY-MM-DD/ XX 
XXXXXXXXXX XXXXXXXXXXXX 
 
 
XXXXXXXX 
V5/Week 8 
YYYY-MM-DD/ XX 
XXXXXXXXXXXXXX 
 
 
 
 
 
 
... 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 133 out of 143 
 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.1 Food Diary. Calcium-rich Nutrients Consumption 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Time Point 
Date of Assessment/ Study Day 
Number of Daily Calcium Servings 
XXX/XX/XXXXX 
14/F/A/NHL 
XXXXXXXX 
Day 1 
YYYY-MM-DD/ XX 
X 
 
 
 
Day 2 
YYYY-MM-DD/ XX 
X 
 
 
 
Day 3 
 
Not Assessed 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
XXXXXXXX 
Day 1 
YYYY-MM-DD/ XX 
X 
 
 
 
Day 2 
YYYY-MM-DD/ XX 
X 
 
 
 
Day 3 
YYYY-MM-DD/ XX 
X 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 134 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.2 Local Skin Reactions Assessment 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Assessment 
Visit 
Date/ Study Day 
Result 
Change from Baseline 
XXX/XX/XXXXX 
14/F/A/NHL 
LSR Sum Score 
V1 (Day 0) 
YYYY-MM-DD/ XX 
7 @ 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
6 
-1 
 
 
 
V3/Week4 
 
Not Done 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator assessment of 
erosion/ulceration in lesional 
area 
V1 (Day 0) 
YYYY-MM-DD/ XX 
2 (Moderate) @ 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
1 (Mild) 
 
 
 
 
V3/Week4 
 
Not Done 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator assessment of 
vesicles in lesional area 
V1 (Day 0) 
YYYY-MM-DD/ XX 
3 (Severe) @ 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
2 (Moderate) 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
2 (Moderate) 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
LSR=Local Skin Reactions. 
@ indicates baseline assessment. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 135 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.3 Vital Signs 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter (Units) 
Visit 
Date of Assessment/ Study 
Day 
Result 
Reference Range 
Change from 
Baseline 
XXX/XX/XXXXX 
14/F/A/NHL 
Systolic Blood 
Pressure (mm Hg) 
V1 (Day0) 
YYYY-MM-DD/ XX 
XXX @ 
XXX - XXX 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
XXX 
XXX - XXX 
XX 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XXX L 
XXX - XXX 
XX 
 
 
 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
Diastolic Blood 
Pressure (mm Hg) 
V1 (Day0) 
YYYY-MM-DD/ XX 
XX @ 
XXX - XXX 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
XX * 
XXX - XXX 
X 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX 
XXX - XXX 
X 
 
 
 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit.  
@ indicates baseline assessment. * indicates notable value. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 136 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.4 Electrocardiogram 
All Enrolled subjects  
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter 
(Units) 
Visit 
Date of Visit/ 
Study Day 
Result 
Change from 
Baseline 
Findings 
Comments/ Technical 
Quality 
XXX/XX/XXXXX 14/F/A/NHL 
General 
Assessment 
V1 (Day0) 
YYYY-MM-DD/ XX 
Normal @ 
 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
Abnormal NCS 
 
XXXXXXXX; XXXXX 
XXXXXXXXXXXXXXX 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
Abnormal NCS 
 
 
 
 
 
 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
RR Interval 
(msec) 
V1 (Day0) 
YYYY-MM-DD/ XX 
XX @ 
 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX * 
XX 
 
 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
XX 
XX 
 
 
 
 
 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit. CS = Clinically Significant. NCS = Not Clinically Significant. 
@ indicates baseline assessment. * indicates notable value.  
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 137 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.5 Physical Parameters 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter (Units) 
Visit 
Date of Visit/ Study Day 
Result 
Change from Baseline 
XXX/XX/XXXXX 
14/F/A/NHL 
Weight (kg) 
V1 (Day0) 
YYYY-MM-DD/ XX 
XX.X @ 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
XX.X 
X 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X 
X 
 
 
 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
Height (cm) 
V1 (Day0) 
YYYY-MM-DD/ XX 
XXX.X @ 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
XXX.X 
X 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XXX.X 
X 
 
 
 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BMI (kg/m2) 
... 
... 
 
 
 
 
 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 138 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.6 Physical Examination 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Examination 
Visit 
Date of Visit/ Study Day 
Result 
XXX/XX/XXXXX 
14/F/A/NHL 
Abbreviated Physical 
Examination 
Scr V1 
YYYY-MM-DD/ XX 
Normal 
 
 
 
V1 (Day 0) 
YYYY-MM-DD/ XX 
Abnormal NCS 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
Normal 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
Not Done 
 
 
 
... 
... 
... 
 
 
 
 
 
 
 
 
Complete Dermatological 
Examination 
Scr V1 
YYYY-MM-DD/ XX 
Abnormal CS 
 
 
 
V1 (Day 0) 
YYYY-MM-DD/ XX 
Normal 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
Normal 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
Normal 
 
 
 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
CS = Clinically Significant. NCS = Not Clinically Significant. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 139 out of 143 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.7 Physician Global Assessment of Psoriasis Severity 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Date/ Study Day 
Result 
Change from Baseline 
 
Treatment Success 
XXX/XX/XXXXX 
14/F/A/NHL 
Scr V1 
YYYY-MM-DD/ XX 
3 - Moderate 
 
 
 
 
Scr V2 
YYYY-MM-DD/ XX 
3 – Moderate 
 
 
 
 
V1 (Day 0) 
YYYY-MM-DD/ XX 
3 - Moderate @ 
 
 
 
 
V2/Week2 
YYYY-MM-DD/ XX 
2 - Mild 
-1 
 
 
 
V3/Week4 
 
Not Done 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
XXX/XX/XXXXX 
15/M/W/HL 
Scr V1 
YYYY-MM-DD/ XX 
3 – Moderate 
 
 
 
 
Scr V2 
YYYY-MM-DD/ XX 
3 – Moderate @ 
 
 
 
 
V1 (Day 0) 
 
Not Done 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
0 - Clear 
-3 
Yes 
 
 
V5/Week 
YYYY-MM-DD/ XX 
0 - Clear 
-3 
Yes 
... 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
L = below lower reference limit. H = above upper reference limit.  
@ indicates baseline assessment. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
Treatment success is defined as at least 2-point decrease from Baseline in the PGA on the trunk, limbs, and scalp. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 140 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.8 Body Surface Area Involvement 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Parameter (Units) 
Visit 
Date/ Study Day 
Result 
Change from Baseline 
 
XXX/XX/XXXXX 
14/F/A/NHL 
Scalp BSA psoriatic involvement (%) 
Scr V1 
YYYY-MM-DD/ XX 
XX.X 
 
 
 
 
Scr V2 
YYYY-MM-DD/ XX 
XX.X 
 
 
 
 
V1 (Day 0) 
YYYY-MM-DD/ XX 
XX.X @ 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X 
XX.X 
 
 
 
V5/Week8 
 
Not Done 
 
 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
 
Neck, Trunk and/or Limbs BSA 
psoriatic involvement (%) 
Scr V1 
YYYY-MM-DD/ XX 
XX.X 
 
 
 
 
Scr V2 
YYYY-MM-DD/ XX 
XX.X @ 
 
 
 
 
V1 (Day 0) 
 
Not Done 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
XX.X 
XX.X 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
... 
 
 
... 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
BSA=Body Surface Area. 
@ indicates baseline assessment. 
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 141 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.9 Psoriasis Treatment Convenience Scale 
All Enrolled subjects  
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Visit 
Date/ Study Day 
Parameter/Question 
Score/Answer 
XXX/XX/XXXXX 
14/F/A/NHL 
V2/Week 2 
YYYY-MM-DD/ XX 
PTCS Total Score 
XX 
 
 
 
 
1. How easy was the treatment to apply to the skin? 
X 
 
 
 
 
2. How greasy was the treatment when applying it to the skin? 
X 
 
 
 
 
3. How moisturized did your skin feel after applying the 
treatment? 
Not Done 
 
 
... 
 
... 
... 
 
 
 
 
 
 
 
 
V3/Week4 
YYYY-MM-DD/ XX 
PTCS Total Score 
XX 
 
 
 
 
1. How easy was the treatment to apply to the skin? 
X 
 
 
 
 
2. How greasy was the treatment when applying it to the skin? 
X 
 
 
 
 
3. How moisturized did your skin feel after applying the 
treatment? 
Not Done 
 
 
 
 
... 
... 
 
 
 
 
 
 
 
 
V5/Week8 
YYYY-MM-DD/ XX 
PTCS Total Score 
XX 
 
 
 
 
1. How easy was the treatment to apply to the skin? 
X 
 
 
 
 
2. How greasy was the treatment when applying it to the skin? 
X 
 
 
 
 
3. How moisturized did your skin feel after applying the 
treatment? 
Not Done 
 
 
 
 
... 
... 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
PTCS=Psoriasis Treatment Convenience Scale. Question 1: From 1 = Very difficult to 10 = Very easy. Question 2: From 1 = Very greasy to 10 = Not greasy. 
Question 3: From 1 = Not moisturized to 10 = Very moisturized. Question 4: From 1 = Very greasy to 10 = Not greasy. Question 5: From 1 = Very 
disturbing to 10 = Not disturbing. Question 6: From 1 = Not satisfied to 10 = Very satisfied.  
PTCS total score is the sum of the scores on questions 1 to 5.  
^ indicates reported visit is different from the analysis visit after windowing was performed. 
 
Path to the program code, date and time of output/ Datasets used 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 142 out of 143 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.10 Pharmacokinetic Concentrations 
All Enrolled subjects 
Page Х of Х 
 
Country/Site 
ID/ Subject 
ID 
Age(Years)
/ 
Sex/Race/ 
Ethnicity 
Analyte 
Visit 
Time Point 
Date, Time of Sample/  
Study Day/ Relative Time 
(hours) 
Date, Time of Last 
Administration of 
Study Drug/  
Study Day 
Result 
Reason if Not 
Done 
XXX/XX/XXXXX 
14/F/A/NHL 
Betamethasone 
17P plasma 
concentration 
(pg/mL) 
Scr V2 
 
 
 
XX.X 
 
 
 
 
V2/Week2 Pre-Dose 
YYYY-MM-DD HH:MM/ XX 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
V3/Week4 Pre-Dose 
YYYY-MM-DD HH:MM/ XX (-X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
1h Post-Dose 
YYYY-MM-DD HH:MM/ XX (X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
3h Post-Dose 
YYYY-MM-DD HH:MM/ XX (X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
5h Post-Dose 
YYYY-MM-DD HH:MM/ XX (X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
V5/Week8  
YYYY-MM-DD HH:MM/ XX 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
BDP plasma 
concentration 
(pg/mL) 
Scr V2 
 
 
 
XX.X 
 
 
 
 
V2/Week2 Pre-Dose 
YYYY-MM-DD HH:MM/ XX 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
V3/Week4 Pre-Dose 
YYYY-MM-DD HH:MM/ XX (-X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
1h Post-Dose 
YYYY-MM-DD HH:MM/ XX (X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
3h Post-Dose 
YYYY-MM-DD HH:MM/ XX (X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
5h Post-Dose 
YYYY-MM-DD HH:MM/ XX (X.XX) 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
V5/Week8  
YYYY-MM-DD HH:MM/ XX 
YYYY-MM-DD HH:MM/ XX 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
... 
... 
... 
... 
... 
... 
 
 
 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
BDP=Betamethasone dipropionate; BLQ=Below Limit of Quantification. 
 
Path to the program code, date and time of output/ Datasets used 
 
 
 
 
 


 
SF_STAT001_ver 2_Eng 
Approval Date 19 July 2017 
MC2-01-C6_STATISTICAL ANALYSIS PLAN_Final 3.0_07 September 2020  
APPENDIX 1 TFLs Shells 
 
 
CONFIDENTIAL AND PROPRIETARY 
Data MATRIX Ltd. 
Page 143 out of 143 
 
 
 
MC2 Therapeutics 
MC2-01-C6 
Listing 16.2.9.11 Pharmacokinetic Parameters 
PK population 
Page Х of Х 
 
Country/Site ID/ 
Subject ID 
Age(Years)/ 
Sex/Race/ 
Ethnicity 
Analyte 
Parameter (Units) 
Result 
Reason Not Estimated 
XXX/XX/XXXXX 
14/F/A/NHL 
BDP 
Cmax (pg/mL) 
XX.X 
 
 
 
 
Tmax (h) 
X.XX 
 
 
 
 
AUC0-5 (h*pg/mL) 
NE 
XXXXXXXXXXXX XXXXXXX 
 
 
 
AUC0-t (h*pg/mL) 
NE 
XXXXXXXXXXXX XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Betamethasone 17-propionate 
Cmax (pg/mL) 
XX.X 
 
 
 
 
Tmax (h) 
X.XX 
 
 
 
 
AUC0-5 (h*pg/mL) 
XX.X 
 
 
 
 
AUC0-t (h*pg/mL) 
XX.X 
 
 
 
 
 
 
 
 
 
... 
... 
... 
 
 
 
 
 
 
 
 
Country: CZE=Czech Republic, HUN=Hungary, DEU=Germany; Sex: F=Female, M=Male; 
Race: A=Asian, B=Black or African American, W=White, O=Other; Ethnicity: HL=Hispanic or Latino, NHL=Not Hispanic or Latino. 
BDP=Betamethasone dipropionate, NE=Not Estimated. 
 
Path to the program code, date and time of output/ Datasets used