Clinical trial NCT03462927
Conditions: Psoriasis Vulgaris
Sponsor: MC2 Therapeutics
Start date: 2018-02-08; Completion date: 2018-08-04
Enrollment: 63 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a phase 2, randomised, open-label, parallel-group, multicentre trial in which MC2-01 cream and calcipotriene \[CAL\]/betamethasone \[BDP\] ointment (comparator) is investigated in subjects 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, the MC2-01 cream will be compared to a marketed calcipotriene \[CAL\]/betamethasone dipropionate \[BDP\] ointment. The purpose of the trial, is to determine the pharmacokinetic parameters of MC2-01 cream and the comparator under maximum use conditions.

Arms: arm 1: MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%). arm 2: CAL/BDP ointment (w/w 0.005%/0.064%).
Interventions: intervention 1: MC2-01 Cream intervention 2: CAL/BDP combination
Intervention descriptions: intervention 1: MC2-01 (calcipotriene/betamethasone dipropionate, w/w 0.005%/0.064%) intervention 2: Calcipotriene/betamethasone (calcipotriene/ betamethasone dipropionate, w/w 0.005%/0.064%)

Protocol documents:
Prot_000.pdf: 
MC2 Therapeutics 
 
Protocol MC2-01-C3 
Date: 20 Dec 2017 
 
Clinical Trial Protocol 
 
Trial Title: 
A Randomised, Multicentre, Open-label, Parallel-group 
Maximal Use Trial, Evaluating the Pharmacokinetic Profile 
of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream compared with Active 
Comparator in Subjects with Extensive Psoriasis Vulgaris
  
Investigational product: 
MC2-01 (calcipotriene/betamethasone dipropionate, w/w 
0.005%/0.064%) Cream 
 
Active Comparator: 
Taclonex® (calcipotriene and betamethasone dipropionate, 
w/w 005%/0.064%) Ointment 
 
Protocol No: 
MC2-01-C3 
 
IND: 
127152 
 
Development phase: 
2 
 
Documents status: 
Final 
 
Document version: 
Version 3.0 
 
Document date:  
20 December 2017 
 
  
 
 
 
 
Sponsor: 
 
 
Drug Delivery Solutions Ltd (part of MC2 Therapeutics) 
 
 
 
 
c/o Agern Alle 24-26 
 
 
 
 
2970 Hørsholm 
 
 
 
 
Denmark 
 
 
 
 
(“MC2”) 
 
 
Property of MC2 Therapeutics 
Confidential 
The confidential information provided in this document is for use by parties directly involved in this 
investigation. This document is delivered in confidence that such information will not be copied or 
made available to any third party without the written consent of MC2 Therapeutics   


MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
- 2 - 
CLINICAL TRIAL PROTOCOL APPROVAL 
Product: MC2-01 (calcipotriene/betamethasone dipropionate) cream 
Protocol number: MC2-01-C3 
Protocol title: A Randomised, Multicentre, Open-label, Parallel-group Maximal Use Trial, 
Evaluating the Pharmacokinetic Profile of the Active Ingredients and their Metabolites after 
application of MC2-01 Cream compared with Active Comparator in Subjects with Extensive 
Psoriasis Vulgaris. 
The following persons have approved this clinical trial protocol, which are separate 
document adjoined to this document: 
  
Johan Selmer, MD, VP Medical Affairs, MC2 Therapeutics                          
 
Carol Udell, Senior Director, Clinical Data Management and Biostatistics, Novella Clinical   
 
 
George Han, MD, PhD, International Coordinating Investigator, Department of Dermatology, 
Mount Sinai Beth Israel                             
 
 
 
 
 


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


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


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


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


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


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


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


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


MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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Sample Size: 
It is planned to enrol approximately 60 subjects with the aim to have 25 subjects 
included in the PK population after 4 weeks of treatment in each treatment arm.  
The choice of sample size in this trial is not based on statistical considerations, 
but rather on regulatory considerations with respect to common practice in 
maximum use studies evaluating pharmacokinetic profiles and evidence of HPA 
safety 
Trial Population: 
Generally healthy males or non-pregnant females, at least 18 years of age, with 
a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 6 months 
duration, with a Physician Global Assessment (PGA) of disease severity of at 
least moderate on the trunk, limbs and/or scalp and a treatment area between 
20% and 30% of the BSA, excluding psoriatic lesions on the face, genitals, and 
intertriginous areas. 
Investigational Product(s): 
MC2-01 cream (CAL and BDP, w/w 0.005%/ 0.064%).  
Reference Product(s): 
CAL/BDP ointment (w/w 0.005%/0.064%). Approved in the United States 
(US) as Taclonex® Ointment and in rest of the world as Daivobet® 
Ointment/Dovobet® Ointment. 
Pharmacokinetics Evaluation 
Criteria: 
Blood samples for PK assessments will be collected at 
• 
SV2 (baseline sample)   
• 
Week 2 
• 
Week 4 and for subjects assigned to the MC2-01 cream at Week 8; 
before application of trial medication and then at 0.5, 1, 2, 3, 5, and 7 
hours after the application.  
The samples will be assayed for concentrations of the active ingredients (BDP 
and CAL) and for their main metabolites; betamethasone 17-propionate and 
MC1080, respectively. 
HPA axis and calcium 
metabolism Evaluation 
Criteria: 
For subjects assigned to the MC2-01 cream, the endpoint for the HPA axis 
evaluation will be a serum cortisol level of 18 µg/dL or less at 30 minutes after 
ACTH challenge at Week 4 and Week 8: 
The primary response criteria for calcium metabolism will be changes from 
Baseline to Week 4 and Week 8 in: 
• 
Albumin-corrected serum calcium; 
• 
24-hour urinary calcium excretion; 
• 
Ratio of urinary calcium to creatinine. 


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


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


MC2 Therapeutics 
Clinical Trial Protocol 
Protocol MC2-01-C3 
20 December 2017 
 
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2.0 
INTRODUCTION   
2.1 
Background 
Psoriasis is a common, immune-mediated, inflammatory skin disease that is found world-wide. 
The prevalence of diagnosed psoriasis in the US is approximately 3%1 whereas the prevalence in 
Europe varies anywhere from 0.6 to 6.5%2 with an average of approximately 3%3. The clinical 
course is unpredictable but in most cases, psoriasis is a chronically remitting and relapsing disease. 
Chronic stable plaque psoriasis (psoriasis vulgaris) is the most common form of the disease, 
accounting for 85-90 % of cases4. Plaque-type psoriasis or psoriasis vulgaris is the most common 
form of the disease, and manifests as raised, red, scaly patches with silver scales. The lesions are 
usually distributed symmetrically, and occur most commonly on the extensor parts of elbows and 
knees; scalp, lumbosacral region and umbilicus5. Patients with psoriasis have reduced quality of 
life with reduced levels of employment and income6, and studies have shown that patients with 
psoriasis are emotionally and physically impaired by their disease comparable to that seen with 
cancer, heart disease, rheumatoid arthritis, diabetes or depression7;8. 
Individuals with psoriasis appear to be at an elevated risk of developing other chronic and serious 
health conditions, such as metabolic syndrome/type 2 diabetes, cardiovascular disease, psoriatric 
arthritis and other chronic inflammatory diseases9;10 
There is no cure for psoriasis. The goal of treatment is to reduce or eliminate its signs and 
symptoms. Mild to moderate disease is often treated with topical therapies. Among topical 
therapies, a combination treatment of a Vitamin D analog and a topical glucocorticosteroid has 
become especially popular. Several studies show that the combination of Calcipotriene (CAL) and 
betamethasone (BDP) is superior to each of the single agent11-12.There is strong scientific rationale 
for the combination of vitamin D and glucocorticosteroids both with respect to efficacy and 
safety13-15, and combination treatment with a Vitamin D analog and a topical corticosteroid is 
recommended in both American and European guidelines16-19 
CAL and BDP are incompatible in an aqueous environment, since CAL requires basic conditions 
to maintain stability while betamethasone requires acidic conditions. Currently marketed products 
are therefore restricted to non-aqueous, oil-based formulations. 
The sponsor has developed the MC2-01 cream containing the fixed dose combination 0.005 w/w% 
CAL (as anhydrate) and 0.064 w/w% BDP using the proprietary PADTM Technology which 
protects the drug substances from degradation during storage. The MC2-01 cream is easy to apply, 
and the cosmetic appearance is that of a white, easily-spreadable cream that absorbs completely 
into the skin a few minutes after application. It is expected that MC2-01 cream will differentiate 
from marketed formulations of CAL/BDP by patient preference for the cream. 


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


MC2 Therapeutics 
Clinical Trial Protocol 
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20 December 2017 
 
- 16 - 
To evaluate the safety of the MC2-01 cream, all adverse events (AEs), reported by the subject or 
observed by the investigator, are recorded. In addition, any effects resulting from systemic 
absorption of the active components, BDP and CAL, are evaluated by assessing adrenal function 
and calcium metabolism, respectively. Adrenal function can therefore be measured by injection 
of a synthetic subunit of ACTH into the subject, and then measuring the production of cortisol by 
the adrenal glands in response to this. In the present study, enrolled subjects in the MC2-01 arm 
of the study will be subjected to an ACTH-challenge test before and after 4 and 8 weeks’ 
treatment.  
Overdosage with topical CAL can cause hypercalcemia20 due to the systemic absorption of CAL, 
which then affects calcium metabolism as it is a vitamin D analogue. However, extensive 
experience with topical use of CAL in psoriasis has demonstrated no significant impact on 
calcium metabolism, when used in the recommended amounts (maximum weekly dose in adults 
of 100 g of a 50 mcg/g concentration). Doses up to 300 g have been used with serum calcium 
remaining within the reference range21. Calcium metabolism will be evaluated in the present 
study by measurement of albumin corrected serum calcium, phosphate, alkaline phosphatase and 
plasma PTH before, during and after treatment. A 24-hour urine sample will be collected and the 
urinary calcium phosphate, sodium and creatinine will be measured and the urinary 
calcium:creatinine and phosphate:creatinine ratios will be calculated. It is well-established that 
there is a relationship between dietary calcium intake and the urinary calcium excretion in 
adults22. The urinary excretion of calcium has been reported to increase by 6-19 mg with each 
additional 100 mg of calcium intake22;23. Subjects will not be asked to change their diet during 
the study, but in order to limit diet-related variability in urinary calcium excretion, their normal 
consumption of calcium-rich foods will be reviewed and should be kept constant during 3 days 
prior to and during each 24-hour urinary collection. Considering that dairy products account for 
the majority of the of calcium absorption in most people, this protocol focusses on the intake of 
dairy products. The subjects will keep a diary of the daily intake of dairy products, calcium-
fortified products (e.g. bread, cereals, orange juice or soy milk) and other specified calcium-rich 
products. The number of daily servings of calcium defined as 240 mL (one US cup) in dairy 
products such as milk or yoghurt or of a calcium-fortified product with corresponding calcium 
content (300 mg calcium per 240mL/one US cup) or 42g (1.5 ounces) of cheese. As an extreme 
calcium intake has been shown to significantly increase urinary excretion of calcium, subjects 
will be instructed not to consume more than five daily calcium servings (i.e. 1500 mg calcium). 
The combination of high calcium intake with vitamin D supplementation significantly increases 
urinary calcium. Hence the use of calcium or vitamin D supplements were excluded in this study 
with the exception of stable doses of oral vitamin D (up to 400 IU/day) at baseline with no dose 
adjustment during the study period. Systemic safety of MC2-01 cream on calcium metabolism 
and HPA axis will be assessed at Week 4 and Week 8. Experience with the current commercially 
available fixed-dose combinations of CAL and BDP has shown that effects on HPA axis 
suppression or calcium homeostasis are infrequent events. For this reason, post-Baseline HPA 


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axis suppression and calcium homeostasis testing will be performed only in subjects receiving 
the MC2-01 cream, without any comparison to the reference compound.  
 
Data from this trial, together with the measurements of albumin-corrected serum calcium and the 
calcium:creatinine ratio in urine samples in the phase 3 trial with MC2-01 cream are expected to 
provide adequate information with respect to the systemic safety of the MC2-01 cream. 
 
2.3 
Benefit-risk Assessment 
The subject population will be composed of subjects with psoriasis that is at least moderate in 
severity according to PGA and involves 20-30% of body surface area (BSA), excluding face, 
genitals and intrigenous areas, in order to evaluate the trial medication under maximum use 
conditions.  
The active ingredients in the investigational products (CAL and BDP) are known to be effective 
for the treatment of psoriasis. The safety and efficacy profiles for marketed products with these 
ingredients (formulated as ointment, gel/topical suspension and more recently aerosol foam) are 
well known.  
MC2-01 cream contains the same active ingredients at identical concentrations of CAL and BDP 
as the marketed products (w/w 0.005%/0.064%) but in a novel cream formulation that is expected 
to provide better cosmetic acceptability to patients than the currently available formulations.  
The side effects reported with CAL/BDP topical formulations are mild and reversible upon 
stopping therapy. It is therefore not considered necessary to have analysis of calcium homeostasis 
prior to initiation of treatment. Subjects in this trial will be monitored for both systemic and local 
safety during the trial.  
Clinical signs or symptoms of systemic safety (e.g., hypercalcemia, HPA axis suppression, or 
cardiac safety) will be part of the periodic assessment of subjects throughout this trial. In addition, 
for subjects assigned to the MC2-01 Cream, an ACTH challenge test supplemented with 
measurement of albumin corrected calcium, and total calcium excretion will be performed at Week 
4 and Week 8. 
A cream formulation of CAL and BDP may benefit subjects by providing improved convenience 
and ease of use resulting in increased patient adherence to therapy which will improve real-life 
treatment outcome24. 
3.0 
TRIAL OBJECTIVES AND PURPOSE 
The primary objective is to evaluate the pharmacokinetic profile of the active ingredients after 
application of MC2-01 cream and their main metabolites, and compare with the active 


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


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


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


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• For subjects assigned to the MC2-01 cream:  
The proportion of subjects with treatment success, defined as a minimum 2-point 
decrease from Baseline in the PGA on the trunk, limbs, and scalp at Week 8. 
• For all subjects:  
Subject assessment of treatment convenience at Week 4 using a Psoriasis Treatment 
Convenience Scale.  
5.0 
SELECTION OF TRIAL POPULATION 
5.1 
Subject Population 
A sufficient number of subjects will be enrolled in order to provide 25 subjects in each treatment 
arm, who are included in the PK analysis at Week 4. An individual subject will be allowed to 
participate in the trial one time only. A rationale for the choice of sample size is provided in Section 
8.2 of this protocol. 
Each potential subject will sign and date an informed consent document (ICF) before any trial-
specified procedures are performed. Subjects will provide authorisation for use of their personal 
data in accordance with the applicable regulations regarding privacy and data protection.  
5.2 
Inclusion Criteria 
Subjects must meet all the following criteria to be eligible for participation in the trial: 
1. 
Have provided written informed consent. 
2. 
Generally healthy males or non-pregnant females, of any race or ethnicity, who are at least 
18 years of age at the time of screening.   
3. 
At Visit 1/Day 0, have a clinical diagnosis of plaque psoriasis (psoriasis vulgaris) of at least 
6 months duration involving trunk, limbs and/or scalp that is amenable to topical treatment 
with a maximum of 100 g of trial medication per week. 
4. 
Have a PGA of severity of at least moderate on the trunk, limbs and/or scalp, excluding 
psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0. 
5. 
Have a treatment area between 20% and 30% of the BSA on the trunk, limbs and/or scalp, 
excluding psoriatic lesions on the face, genitals, and intertriginous areas, at Visit 1/Day 0. 
6. 
Female subjects must be of either: 
• Non-childbearing potential, i.e., post-menopausal for a least 1 year or have a clinical 
history of sterility (e.g., hysterectomy or tubal ligation) or, 
• Childbearing potential with a negative urine pregnancy test prior to initiation of trial 
treatment, to rule out pregnancy. 


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7. 
Female subjects of childbearing potential must be willing to use effective contraception at 
trial entry and until completion. Effective contraception is defined as follows:  
• Oral/implant/injectable/transdermal/estrogenic vaginal ring contraceptives, 
intrauterine device, condom with spermicide, diaphragm with spermicide.  
• Abstinence or partner’s vasectomy are acceptable if the female agrees to implement 
one of the other acceptable methods of birth control if these conditions do not any 
longer apply. 
5.3 
Exclusion Criteria 
Subjects who fulfil any of the following criteria will be ineligible to participate in the trial: 
1. 
Have a current diagnosis of unstable forms of psoriasis, including erythrodermic or 
pustular psoriasis. 
2. 
Other inflammatory skin disease in the treatment area that may confound the evaluation of 
the psoriasis vulgaris (e.g., atopic dermatitis, contact dermatitis, tinea corporis);  
3. 
Presence of pigmentation, extensive scarring, pigmented lesions or sunburn in the 
treatment areas, which could interfere with the rating of efficacy parameters;  
4. 
Planned excessive or prolonged exposure to either natural or artificial sunlight, including 
tanning booths, sun lamps, etc.  
5. 
Use of phototherapy (psoralen + ultraviolet A radiation [PUVA] and ultraviolet B 
radiation [UVB]) within 4 weeks prior to Visit 1/Baseline and during the trial; 
6. 
Current or past history of disorders of calcium metabolism associated with 
hypercalcemia, vitamin D toxicity, severe renal insufficiency, or severe hepatic disorders; 
7. 
Oral calcium supplements, vitamin D supplements, bisphosphonates or calcitonin within 
4 weeks prior to Visit 1/Day 0 during the trial period.  
Note: Stable doses of oral vitamin D supplementation ≤400 IU/day are permitted 
provided there are no dose adjustments during the trial period; 
8. 
Planned initiation of, or changes to concomitant medication that could affect calcium 
metabolism (e.g., antacids, thiazide and/or loop diuretics, antiepileptics) during the trial; 
9. 
Planned initiation of, or changes to, concomitant estrogen therapy during the trial; 
10. Strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., clarithromycin, 
telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, 
lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir) within 4 weeks prior to Vist 1/Day 
0 and during the trial period; 
11. Use of topical treatments (eg, corticosteroids, vitamin D analogs, retinoids, PDE4 
inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar), except for emollients 


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and non-medicated shampoos, with a possible effect on psoriasis within 2 weeks prior to 
Visit 1/Day 0 and during the trial period;  
12. Systemic treatment with biological therapies (whether marketed or not marketed), with a 
possible effect on psoriasis vulgaris within the following time period prior to Visit 1/Day 
0 and during the trial period; 
• etanercept – within 4 weeks 
• adalimumab, alefacept, infliximab – within 8 weeks 
• ustekinumab – within 16 weeks 
• other products – within 4 weeks/5 half-lives (whichever is longer) 
13. Initiation of, or expected changes to, concomitant medication that may affect psoriasis (e.g., 
beta-blockers, chloroquines, lithium, and angiotensin converting enzyme [ACE] inhibitors) 
and during the trial period; 
14. Any of the following conditions, whether known or suspected: 
• depression and endocrine disorders (e.g. Cushing’s disease, Addison’s disease, 
diabetes mellitus) known to affect cortisol levels or HPA axis integrity  
• Non-nocturnal sleep patterns (e.g. night shift workers); 
15. Use of systemic medication that suppresses the immune system (e.g, methotrexate, 
retinoids, PDE4 inhibitors, corticosteroids (excluding inhaled, nasal, auricular or ocular 
corticosteroids), ciclosporin [cyclosporine], and other systemic chemotherapeutic 
antineoplastic therapy) within 4 weeks prior to the Visit 1/Day 0 and during the trial 
period; 
16. Have clinical signs of skin infection with bacteria, viruses, or fungi; 
17. Known human immunodeficiency virus (HIV) infection; 
18. Known or suspected of hypersensitivity to any component of the test product or reference 
product; 
19. Have any chronic or acute medical condition that, in the option of the investigator, may 
pose a risk to the safety of the subject, or may interfere with the assessment of safety or 
efficacy in this trial; 
20. Require the use of any concomitant medication that, in the investigator’s opinion, has the 
potential to cause an adverse effect when given with the investigational product or will 
interfere with the interpretation of the trial results; 
21. Females who are pregnant, breast feeding, or planning a pregnancy; 


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22. Participation in another clinical trial or received an investigational product or non-
marketed drug substances within 30 days; 
23. Previously enrolled in this trial; 
24. In the opinion of the (sub)investigator, the subject is unlikely to comply with the clinical 
trial protocol; 
 
5.4 
Withdrawals and Discontinuation of Treatment 
In accordance with legal requirements and International Conference on Harmonization (ICH) – 
Good Clinical Practice (GCP) guidelines, every subject has the right to refuse further participation 
in this trial at any time and without providing reasons (see also Section 9.2).  A subject's 
participation is to be terminated immediately upon his/her request.  The investigator should seek 
to obtain the reason and record this on the electronic case report form (eCRF) whenever possible. 
If, at the time of refusal, a trial product has already been administered, the subject should be 
advised on follow-up safety evaluations.  
If HPA axis is suppressed at Visit 1/Day 0 or Week 4, the subject should be contacted and the 
application with the investigational product (IP) should be discontinued (see Section 7.9.2 and 
Section 7.16).  
If albumin corrected serum calcium is above upper limit at Visit1/Day 0, the application with the 
investigational product (IP) should be discontinued (see Section 7.9.2).   
In the case of an SAE or development of a condition that would have met the trial safety-related 
exclusion criteria, the subject should be evaluated by the investigator. The investigator should use 
his/her discretion to determine whether the subject should continue treatment with the IP.  
A subject may be withdrawn from the trial at any time at the discretion of the investigator. The 
reasons for early termination are to be fully documented on the eCRF. 
In addition, the MC2 reserves the right to end or suspend the trial at any time (see Section 9.2). 
If a subject withdraws from the trial, all efforts will be made to complete a final evaluation if 
possible. Protocol-specified withdrawal procedures are defined in Section 7.16 Early Termination. 
Subjects discontinued for an AE will be monitored until the AE is resolved, a reasonable 
explanation is provided for the event, or the subject is referred to his/her own primary medical 
doctor. The specific AE in question will be recorded on the appropriate eCRF. 


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5.5 
Replacement Policy 
After trial enrolment, has been completed, subjects who prematurely discontinue the trial after 
randomisation can be replaced if necessary to ensure 25 subjects in both treatment arms are 
included in the PK population at Week 4. 
6.0 
TRIAL TREATMENTS 
6.1 
Investigational Product  
MC2-01 cream is a combination product, calcipotriene and betamethasone dipropionate, 
administered as a cream formulation for topical administration. One concentration of the trial 
product will be studied: calcipotriene (w/w 0.005%) and betamethasone (w/w 0.064%, as 
dipropionate). The list of inactive ingredients present in MC2-01 cream is presented in the 
Investigator Brochure. 
6.2 
Active Comparator 
The active comparator is CAL and BDP Ointment, 0.005%/0.064%, approved in the US as 
Taclonex Ointment and in the rest of the world as Daivobet® Ointment/Dovobet® Ointment.  
Taclonex® Ointment contain the following inactive ingredients: 
• mineral oil,  
• polyoxypropylene stearyl ether  
• all-rac-alpha-tocopherol 
• butylhydroxytoluene 
• white petrolatum  
  
6.3 
Dosing Regimen 
Subjects are to apply the trial product topically once daily, preferably in the evening, to affected 
areas on the scalp and the trunk (including the neck) and/or limbs, i.e., arms (including the back 
of the hands) and/or legs (including the buttocks and the top of the feet). The face, genitals, and 
intertriginous areas should not be treated with the investigational product. The first application is 
done under the supervision and instruction of the trial staff. 
All subjects are instructed to apply the dose of trial medication in the morning on the day before 
the Week 2, Week 4 and for subjects assigned to the MC2-01 cream also at the Week 8 visit. On 
the day of the visit, the subjects should not apply any investigational product before the visit 
Subjects are to record the date and time of application in the subject dosing diary. The weekly dose 
is not to exceed 100 g for the MC2-01 cream or for the comparator. The treated area should not 
exceed 30% of the BSA.  
Detailed application instructions will be provided in the subject instructions.  


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6.4 
Dose Modification 
Until Week 4:  
Subjects classified as clear at the Week 2 visit are to continue use of the treatment unless 
investigator finds further treatments unacceptable.  
After Week 4:  
Subjects classified as clear at any of the on-treatment visits may stop the treatment at the 
investigator’s discretion. They should remain in the trial and attend all visits up to and including 
the follow-up visit. The IPs will continue to be dispensed to the subject, and treatment may be 
restarted at the subject’s discretion. The subject should not discontinue treatment themselves 
between visits, but is only allowed to stop using the treatment on the advice of the investigator at 
a scheduled visit. 
6.5 
Packaging, Labeling and Storage 
Medication labels for the investigational products will comply with the legal requirements of the 
country where the trial is performed and be printed in the local language.  
The investigational products will be supplied by MC2’s designated vendor and will be stored 
securely at the site under the control of the investigator. The temperature will be monitored and 
documented.    
The MC2-01 cream will be supplied to the clinical site(s) as tubes containing 60 g of product. The 
MC2-01 cream is to be stored at a temperature of 2°- 8°C (35°- 46°F) at the site, and below 25°C 
(below 77°F) after dispensing to the subject. At all times, the MC2-01 cream should be protected 
from light.  
The active comparator will be supplied to the clinical sites as tubes containing 60 g of product. 
The active comparator is to be stored at 20°- 25°C (68° -77°F).  
6.6 
Assignment to Treatment 
6.6.1 
Randomisation 
Randomisation will be performed using a validated system that automates the random assignment 
of treatment groups to randomisation numbers. Treatment assignment will be via a central 
interactive web response (IWR) system in accordance with a pre-planned computer-generated 
randomisation schedule in a 1:1 ratio.  
A subject who fulfils the trial eligibility requirements will be randomly assigned to treatment. 
6.6.2 
Blinding 
This is an open-label trial with the treatment assignment known by the subjects, the investigators 
and their staff, and the clinical research team. No blinding will be performed.   


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6.7 
Prior, Concomitant, and Prohibited Therapy 
All medications, including over-the-counter (OTC) drugs, taken within 30 days prior to the start 
of the trial will be recorded at Screening. Thereafter, a record of all medications and supportive 
therapy taken during the course of the trial will be made. Information regarding the total daily 
dose, route of administration, start and discontinuation dates, and indication are to be recorded on 
the subject’s eCRF. 
6.7.1 
Washout of prohibited medications prior to enrolment 
A washout period must be completed if the subject has been treated with any medication as 
specified in the exclusion criteria (Section 5.3). 
6.7.2 
Prohibited medications during the trial 
Use of any medication that would exclude the subject from participation in the trial (as specified 
in Section 5.3 Exclusion Criteria) is also prohibited during the treatment and follow-up periods, 
which includes medications in the following categories:  
• 
Use of biological psoriasis therapies;  
• 
Use of oral systemic treatments with a possible effect on psoriasis (eg, methotrexate, 
retinoids, PDE4 inhibitors, corticosteroids, and other immunosuppressants). 
• 
Use of phototherapy (PUVA and UVB). 
• 
Use of topical treatments with a possible effect on psoriasis (eg, corticosteroids, vitamin D 
analogs, retinoids, PDE4 inhibitors, salicylic acid, pimecrolimus, tacrolimus, anthralin, tar, 
etc.). 
• 
Initiation of dosing or changes in dosage of drugs that are known to have an effect on 
psoriasis should be avoided. This includes, but is not limited to, beta-blockers, 
chloroquines, lithium, and ACE inhibitors. 
• 
Use of strong systemic cytochrome P450 3A4 (CYP 3A4) inhibitors (e.g., clarithromycin, 
telithromycin, nefazodone, itraconazole, ketoconazole, atazanavir, darunavir, indinavir, 
lopinavir, nelfinavir, ritonavir, saquinavir, tipranavir. 
• 
Emollients on the psoriasis affected areas. 
• 
Any medications with proven or purported activity against psoriasis (including OTC 
medications) should be discussed with the Investigator prior to use. 
6.7.3 
Allowed treatment on the face, skin folds, and genital skin only 
Subjects may receive laser treatment and use an emollient on the face, skin folds, and genital skin. 
6.8 
Treatment Compliance 
Records of trial product used and dosages administered will be kept during the trial. The trial 
monitor will note product accountability during site visits and at the completion of the trial. 


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At all on-treatment visits, the subject will be asked if he/she has used the medication as prescribed. 
If this is not the case, the degree and nature of noncompliance will be specified. In addition, 
subjects will be asked to complete a dosing diary during the treatment period as a measure of 
treatment compliance. Subjects who are consistently noncompliant will be counseled. 
Subjects will be asked to return all used and unused tubes in the outer box at each visit. All returned 
tubes that had been dispensed to a subject and have broken seals will be weighed to determine the 
amount of the investigational product used per treatment phase.  
 
 


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


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a) A washout period of up to 4 weeks must be completed if the subject has been treated with 
anti-psoriatic treatments or other relevant medication, as defined by exclusion criteria. Items 
denoted in [brackets] must be reviewed during screening, to assess if the subject is 
otherwise eligible. Such items must be checked for any change in eligibility status at  
Visit 1/Day 0 after the washout is completed.  
b) Informed consent must be signed both by subject and investigator or designee before any 
trial related procedures are carried out. For subjects requiring a washout period, informed 
consent must be completed prior to washout. 
c) For female subjects of childbearing potential. 
d) Including height and weight  
e) AEs are to be collected from the date of signing informed consent, i.e., during the washout 
period. 
Instruct: At the indicated visits, instruct the subjects as to appropriate trial procedures as 
specified below: 
• Food diary: instruct the subjects on how to use the food diary, especially recording their 
intake of calcium-rich nutrients 
• 24-hour urine collection: instruct the subjects on how to perform the 24-hour urine 
collection. 
 
 


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


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


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


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


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7.4 
Demographics and Medical History 
The following demographic and medical history must be collected:  
• Date of birth 
• Sex 
• Race 
• Ethic origin 
• Complete skin disease history  
• All other current and past medical/surgical conditions within the last 12 months 
• The year diagnosed with psoriasis vulgaris 
The Fitzpatrick skin type will be assessed according to the classification scheme in Table 7-4. 
Table 7-4 
Fitzpatrick Skin Type Classification 
I 
Pale white skin, blue/hazel eyes, blond/red 
hair 
Always burns, does not tan 
II 
Fair skin, blue eyes 
Burns easily, tans poorly 
III 
Darker white skin 
Tans after initial burn 
IV 
Light brown skin 
Burns minimally, tans easily 
V 
Brown skin 
Rarely burns, tans darkly easily 
VI 
Dark brown or black skin 
Never burns, always tans darkly 
  
7.5 
Prior and Concomitant Medication 
Review and record prior medication and concomitant medication. 
All medications, including OTC drugs, taken within 30 days prior to the start of the trial will be 
recorded at Screening. Thereafter, a record of all medications and supportive therapy taken during 
the trial will be made. Information regarding the total daily dose, route of administration, start and 
discontinuation dates, and indication are to be recorded on the subject’s eCRF. 
7.6 
Physical Examination 
An abbreviated physical examination and dermatological examination of the skin must be 
performed, including height and weight at Visit 1/Day 0. The height and weight can be self-
reported.  


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


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


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


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7.11 
The Psoriasis Treatment Convenience Scale 
The Psoriasis Treatment Convenience Scale must be completed by the subjects before any other 
assessments are performed. The PRO assessments are to be performed as specified in the visit 
schedule (see Table 7-2, and Table 7-3).  
The aim of the Psoriasis Treatment Convenience Scale is to assess the impact and convenience of 
psoriasis treatment. The scale has been tested for content validity through focus group interview 
with 20 patients and adapted based on the responses. The scale consists of 5 disease-specific, self-
report questions with a recall period of 1 week and rated on a 1-10 scale.  
1. How easy was the treatment to apply to the skin?   
2. How greasy was the treatment when applying it to the skin? 
3. How moisturised did your skin feel after applying the treatment? 
4. How much did treating your skin disrupt your daily routine? 
5. Overall, how satisfied were you with the medical treatment? 
 
7.12 
Investigator Assessments 
The investigator assessments are to be performed by a dermatologist, a physician with at least 
1 year of experience in dermatology, or a Nurse Practitioner or Physician Assistant with at least 
2 years of experience in dermatology. For physicians, Nurse Practitioners and Physician Assistants 
who do not fulfill the requirement regarding dermatological experience, the person must be 
preapproved by the sponsor. The assessments are to be performed as specified in the visit schedule 
Table 7-1, Table 7-2 and Table 7-3. 
7.12.1 
Physician’s global assessment of psoriasis severity 
The Physician’s Global Assessment (PGA) measures the investigator’s or designee’s impression 
of the disease at a single point using a defined, 5-point, static PGA scale (clear, almost clear, 
mild, moderate or severe); see Table 7-5. The PGA assessment will represent the average lesion 
severity on scalp, trunk and limbs (excluding face, genitals, and intertriginous areas). The 
assessments will be based on the condition of the disease at the time of evaluation, and not in 
relation to the condition at a previous visit.  


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Table 7-5 
Physician’s Global Assessment (PGA) 
Score 
Grade 
Definition 
0 
Clear 
Plaque thickening = no elevation or thickening of normal skin 
Scaling = no evidence of scaling 
Erythema = none (no residual red colouration but post-inflammatory 
hypo or hyperpigmentation may be present) 
1 
Almost 
clear 
Plaque thickening = none or possible thickening but difficult to ascertain 
whether there is a slight elevation above normal skin level 
Scaling = none or residual surface dryness and scaling 
Erythema = light pink colouration 
2 
Mild 
Plaque thickening = slight but definite elevation 
Scaling = fine thin scales partially or mostly covering lesions 
Erythema = light red colouration 
3 
Moderate 
Plaque thickening = moderate elevation with rounded or sloped edges 
Scaling = coarse scale layer at least partially covering most lesions 
Erythema = definite red colouration 
4 
Severe 
Plaque thickening = marked or very marked elevation typically with hard or 
sharp edges 
Scaling = non-tenacious or thick tenacious scale predominates, covering most 
or all of the 
lesions 
Erythema = very bright red colouration, extreme red coloration or deep red 
coloration 
 
7.12.2 
Body surface area involvement of psoriasis vulgaris 
The investigator or designee will assess the extent of the subject’s psoriatic involvement on the 
scalp, trunk and limbs (excluding face, genitals, and intertriginous areas).  
The total psoriatic involvement on the scalp, trunk and limbs will be recorded as a percentage of 
the total BSA, estimating that the surface of the subject’s full, flat palm (including the five digits) 
correlates to approximately 1% of the total BSA. If the subject has psoriasis of guttatae character, 
these elements will be part of the estimation of total psoriatic involvement. The purpose of this is 
to obtain an estimate of the area on the trunk and limbs to be treated with trial medication. 


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7.12.3 
Local skin reactions 
The local skin reaction assessment involves signs assessed by the investigator or designee and 
symptom reported by the subject. 
The investigator will assess the treatment area and/or immediate surrounding for the following 
identified signs:  
• Perilesional erythema, scaling, edema, atrophy, vesicles and erosion/ulceration;  
• Lesional vesicles, and erosion/ulceration.  
The intensity of each local skin reaction category is to be graded according to the scale in  
Table 7-6. The most severe intensity observed for each category of the local skin reaction 
assessment is to be recorded. 
 
The subject will assess burning and pain after application. The investigator or designee  
will explain the scores in Table 7-6 and the subject will tell which one to mark.  
Signs and symptoms fulfilling the adverse advent definition should be reported as adverse 
events. 


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Table 7-6 
Local Skin Reaction Scores 
Investigator assessment of the lesional area 
 
0 (absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erosion/ulceration 
in lesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
Vesicles 
in lesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Investigator assessment of the perilesional area 
 
0=absent 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Erythema  
in perilesional area 
None 
Barely visible 
erythema 
Distinct erythema 
Dark red erythema 
Scaling 
in the perilesional area 
None 
Barely visible 
scaling 
Distinct scaling 
Gross  scales 
Edema 
in perilesional area 
None 
 barely palpable 
swelling 
Easily palpable 
swelling 
Gross swelling 
Atrophy 
in perilesional area 
None 
Barely visible 
thinning 
Distinct thinning 
Striae 
Vesicles  
in perilesional area 
None 
Barely visible 
vesicles 
Distinct vesicles 
Bullae 
Erosion/ulceration 
in perilesional area 
None 
Barely visible 
erosion 
Distinct erosion 
Ulceration 
Subject Assessment 
 
0 (absent) 
1 (Mild) 
2 (Moderate) 
3 (Severe) 
Burning 
or 
pain  
after application 
None 
Barely present and 
disappears within 
few minutes 
Distinct and lasts 
for up to an hour 
Pronounced and 
lasts for several 
hours  
 
7.13 
Adverse Events 
7.13.1 
Adverse events assessments 
The investigator or designee is responsible for obtaining, assessing, and documenting all AEs 
during the study. Adverse Events information will be collected from the time of the signature of 
the informed consent form and first trial-related activity performed until the end of the study. An 


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AE is an untoward medical occurrence in any subject during the trial which does not necessarily 
have a causal relationship with the trial drug treatment.  
All AEs will be documented in the eCRF, including a description of each AE, AE relationship to 
trial product administration, start and stop dates, seriousness, severity, action taken and outcome.  
Any AE that meet the serious criteria must be reported on the eCRF and on a separate SAEs report 
form. SAEs must be reported to the United BioSource Corporation (UBC) within 24 hours of 
awareness.  
Throughout the trial, the occurrence of AEs should be sought by nondirective questioning of the 
subject at each visit during the trial. Information on AEs can also be obtained from signs and 
symptoms detected during examination, observations made by the trial site personnel, or 
spontaneous reports from subjects. Pre-existing conditions that worsen during the trial should also 
be recorded as AEs. 
AEs requiring therapy must be treated with recognised standards of medical care to protect the 
health and well-being of the subject. Treatment due to an AE will be recorded in the subject’s 
records and on the appropriate eCRF. 
Any AE that is considered related to the trial product must be followed by the investigator until it 
is resolved or until the medical condition of the subject is stable; all relevant follow-up information 
will be reported to the MC2 or designee. 
The outcome of an AE will be classified as recovered, recovered with sequelae, 
recovering/resolving, ongoing, or death. 
7.13.2 
Timing 
AEs will be collected/assessed during the period from the time of the signature of the informed 
consent form by the subject and first trial-related activity performed.  
7.13.3 
Severity of adverse events 
The investigator is to classify the severity (intensity) of an AE according to the following 
definitions: 
• Mild – The subject was aware of the signs and symptoms but the signs and symptoms were 
easily tolerated and does not interfere with daily activity. 
• Moderate – The signs and symptoms were sufficient to restrict, but did not prevent, usual 
daily activity for the subject. The subject is still able to function.  
• Severe – The subject was unable to perform usual daily activity. 


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The maximum intensity of an AE (mild, moderate, or severe) will be assessed taking into 
account the possible range of intensity of the symptom(s). 
7.13.4 
Relationship of an adverse event to trial treatment 
The investigator is responsible to assess the relationship of an AE to the IP using good clinical 
judgment and the following definitions: 
Not Related 
The AE is clearly explained by another cause not related to the trial 
product administration; the temporal relationship of the AE to IP 
administration makes a causal relationship unlikely, or, concomitant 
medication, therapeutics interventions, or underlying condition provide 
a sufficient explanation for the observed AE 
Possibly Related 
The AE and administration of trial product are temporally related, but 
the AE can be explained equally well by causes other than the trial 
product administration 
Probably Related 
The AE and use of trial product are temporally related, and the AE is 
more likely explained by trial product administration than by other 
causes 
Definitely Related 
The AE and trial product administration are related in time, and a direct 
association can be demonstrated. Concomitant medication, therapeutics 
interventions, or underlying conditions do not provide a sufficient 
explanation for the observed AE 
7.13.5 
Unexpected adverse events 
Any AE assessed as related to the IP will be assessed for expectedness by the sponsor or designee. 
An AE is considered “unexpected” if its nature or severity is not consistent with information in the 
MC2-01 Investigator’s Brochure (for MC2-01 cream)26 or Taclonex® Ointment prescribing 
information27 (for active comparator). 
 “Unexpected” as used in this definition, also refers to AEs that are mentioned in the Investigator’s 
Brochure or product prescribing information as occurring with a class of drugs or as anticipated 
from the pharmacological properties of the drug, but are not specifically mentioned as occurring 
with the particular drug under investigation. 
 
 
 


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7.13.6 
Trial medication overdose 
An overdose of the investigational product, i.e., a dose that is higher than the highest dose under 
clinical investigation or the known therapeutic dose, will be fully documented even if no toxic 
effects were observed and will be considered an AE. 
The maximum weekly dose of the MC2-01 cream and the comparator is 100 g. The treated area 
should not be >30% of the body surface area.  
 
Use above the recommended dose may cause elevated serum calcium, which should rapidly 
subside when treatment is discontinued. Excessive prolonged use of topical corticosteroids may 
suppress the pituitary-adrenal functions, resulting in secondary adrenal insufficiency that is usually 
reversible. In such cases, symptomatic treatment is indicated. 
7.13.7 
Pregnancy 
Any pregnancy occurring from date of the Informed Consent signature until study completion must 
be reported immediately to the MC2 or designee as soon as it becomes known to the investigator 
and not later than within 24 hours of his/her knowledge of the occurrence of the pregnancy (see 
Section 13.2).  
Investigator must actively follow-up, document and report to MC2 or designee the progress of the 
pregnancy until outcome is reached.  
7.13.8 
Serious adverse event 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death 
• Is life-threatening 
• Requires in-patient hospitalisation or prolongation of existing hospitalisation 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect, or is an important medical event 
• Other serious or important medical event  
The death of a subject enrolled in a trial is per se not an event, but an outcome. Any event resulting 
in a fatal outcome must be fully documented and reported, regardless of the causality relationship 
to the IP. 
Any medical important events that may not result in death, be life-threatening, or require 
hospitalisation may be considered an SAE when, based on appropriate medical judgment, they 
may jeopardise the subject or the subject may require medical or surgical intervention to prevent 
one of the outcomes listed in the above definitions.  


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Any pre-planned hospitalisations that are known at the time of signing the ICF will not be recorded 
as SAEs, however they will be recorded as AEs only.  
Any SAE, whether or not deemed drug-related or expected, must be reported immediately to the 
MC2 or designee as soon as it becomes known to the investigator and not later than within 24 hours 
of his/her knowledge of the occurrence of an SAE (see Section 13.2). The investigator will 
document such events in the best possible detail on the SAE Report Form.  
A suspected unexpected serious adverse reaction (SUSAR) is an SAE that is both unexpected 
(not consistent with the current Investigator’s Brochure1 or Taclonex® Ointment prescribing 
information,3, and for which there is evidence to suggest a causal relationship between the drug 
and the SAE. The Institutional Review Board (IRB)/Independent Ethics Committee (IEC) will be 
informed of SUSARS according to local requirements. All investigators participating in the trial 
will also be notified of unexpected SAEs. The sponsor will report SAEs and other events 
requiring expedited reporting to regulatory authorities as required.  
Investigator instructions for reporting SAEs are provided in Section 13.2. 
7.14 
Unscheduled Visit 
An unscheduled visit may be performed at any time during the trial if judged necessary by the 
Investigator, such as for a severe reaction, suspected pregnancy, clinically significant AE, or 
clinically significant local skin reaction result. Details of the event are to be recorded in the 
subject’s records. 
7.15 
Follow-up Visit 
A follow-up visit is required for the following reasons:  
• 
Unresolved related AEs. 
For subjects assigned to the MC2-01 cream: 
• 
If the albumin-corrected serum calcium was above the normal reference range at Week 4 and 
Week 8 a repeat should be done 14 days (± 2 days) after.  
• 
If the HPA axis suppression is noted at Week 8 an ACTH challenge test should be performed 
28 days (± 2 days) after. 
7.16 
Early Termination 
If a subject withdraws from the trial prior to Week 4 and for subjects assigned to the MC2-01 
cream prior to Week 8, the subject is to return to the site for an unscheduled visit. The following 
procedures should be performed:  
• 
Collect all trial materials from the subject. 


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


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


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


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Discontinuations from the trial due to AEs and SAEs will be listed by subject. 
8.8.4 
Other safety variables 
Clinical laboratory values will be reported as complete listings of individual subject data.  
Clinical laboratory data will be summarized by presenting shift tables using extended normal 
ranges (baseline to most extreme post-baseline value), by presenting summary statistics of raw 
data and change from baseline values (means, medians, SDs, ranges), and by the flagging of 
notable values in data listings. 
Data from other tests (e.g., vital signs, ECG results) will be considered as appropriate and listed. 
Notable values will be flagged, and any other information collected will be listed as appropriate. 
Any statistical tests performed to explore the data will be used only to highlight any interesting 
comparisons that may warrant further consideration. 
Vital signs will be summarised at each visit, both as absolute values and as change from Baseline, 
with descriptive statistics. 
8.9 
Analysis of Other Endpoints 
8.9.1 
Physician global assessment 
Investigator ratings of disease severity will be summarised by trial visit using frequency counts 
for each treatment. The proportion of subjects with treatment success, defined as a minimum 2-
point decrease from Baseline in the physician’s global assessment (PGA) on the trunk, limbs, 
and scalp will be summarized. 
8.9.2 
Psoriasis treatment convenience scale 
Subject assessment of treatment convenience at Week 4 using a Psoriasis Treatment Convenience 
Scale will be summarized and further compared between MC2-01 cream and the active comparator 
using mixed effect model with treatment as a systematic effect and study site as a random effect. 
8.10 
Quality of Life Analysis (Not Applicable) 
Not applicable. 
9.0 
CHANGES IN THE PLANNED TRIAL 
9.1 
Protocol Amendments 
Except for administrative changes, any changes or additions to this clinical trial protocol require a 
written protocol amendment that must be approved by the IRB before implementation.  
These requirements for approval should in no way prevent any immediate action from being taken 
by the investigator or MC2 in the interests of preserving the safety of all subjects included in the 
trial. If an immediate change to the protocol is felt to be necessary by the investigator and is 


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implemented for safety reasons, MC2 or designee should be notified and the IRB should be 
informed according to their reporting requirements. 
9.2 
Termination or Suspension of the Trial 
MC2 reserves the right to terminate or suspend the trial at any time. In case of premature 
termination or suspension of the trial, the contract research organization (CRO) project manager 
will promptly inform the investigators, regulatory authorities, and IRBs about the premature 
termination or suspension, including the reason for it. In terminating the trial, MC2 and the 
investigator will ensure that adequate consideration is given to the protection of the subjects’ 
interests. 
10.0 
DATA HANDLING AND RECORD KEEPING 
10.1 
Recording of Data 
10.1.1 
Source documents 
Source data are all the information in original records and copies of original records of clinical 
findings, observations, or other activities in the trial, which are necessary for the reconstruction 
and evaluation of the trial. The identification of any data to be recorded directly on the eCRFs is 
to be considered source data.  
Trial data collection procedures must ensure that each data element can be traced with a high level 
of confidence from its originator or recorder to its representation in the trial database and then to 
its place in the analysis and report of trial results. Once recorded, the trial data must be protected 
from unauthorised modification or deletion, and all authorised modifications and deletions must 
be securely linked in the permanent record with their author, time of change, and reason for change 
(i.e., the audit trail must be maintained). 
The investigator will permit trial-related monitoring, audit(s), IRB/IEC review(s) and regulatory 
inspection(s), with direct access to all the required source records. 
The principal investigator will certify the data to be accurate and complete and will release the 
data for transmittal to MC2 or designee. 
Source records need to be preserved for the maximum period of time permitted by local 
requirements (see Section 10.2). For each subject enrolled, the investigator will indicate in the 
source record(s) that the subject participated in the trial. 
10.1.2 
Case report forms 
The primary data collection tool for the trial is an eCRF designed specifically for the trial. For each 
subject enrolled in the trial, an eCRF will be completed by the trial coordinator and signed by the 
investigator or his/her designate.  


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The investigator will be responsible for ensuring the accuracy of all data entered in the eCRFs. All 
eCRFs are to be completed in a timely manner. 
Errors occurring in the eCRFs will be queried. Queries raised by data reviewers must be addressed 
by site personnel. 
On request, the investigator will provide the MC2 with additional data relating to the trial, or copies 
of relevant source records, duly anonymised (i.e., subject’s name is redacted). 
10.2 
Retention of Documents 
The investigator shall take responsibility for maintaining adequate and accurate source documents 
of all observations and data generated during this trial, including any data clarification forms 
received from the MC2 or designee. Such documentation is subject to inspection by the sponsor 
or its agents, the FDA and/or other regulatory agencies. The investigator is responsible for 
retention of essential documents including the Investigator Trial File until MC2 informs the 
investigator that the documents are no longer to be retained or longer if required by local 
regulations.  
11.0 
QUALITY CONTROL AND QUALITY ASSURANCE 
11.1 
Direct Access to Source Documents 
As specified in the investigator’s agreement, the investigator agrees to allow trial-related 
monitoring, audit(s), IRB/IEC review(s) and regulatory inspection(s), with direct access to all the 
required source records, and to allocate his/her time and the time of his/her staff to the 
auditor/inspector to discuss findings and any issues.  
11.2 
Monitoring Procedures 
The Clinical Trial Monitor will contact and/or visit the investigator site periodically to verify the 
adherence to the protocol, the maintenance of trial-related source records, and the completeness 
and accuracy of all eCRF entries compared to source data. The investigator will cooperate with 
the trial monitor to ensure that any discrepancies that may be identified are resolved. 
11.3 
Audit and Inspection 
The investigator will make all the trial-related source data and records available to a quality 
assurance auditor mandated by the sponsor, or to domestic or foreign regulatory inspectors, after 
reasonable notice. The main purposes of an audit or inspection are to confirm that the rights and 
well-being of the subjects have been adequately protected, and that all data relevant for the 
evaluation of the IP have been processed and reported in compliance with GCP/ICH and applicable 
regulatory requirements. 


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The investigator is to notify the MC2 or designee immediately of any inspection by regulatory 
authorities or IRBs. 
12.0 
ETHICS 
12.1 
Ethical Conduct of the Trial 
This trial must be carried out in compliance with the protocol and the applicable laws and 
regulatory requirements of the appropriate regulatory agency. The trial must be conducted in 
accordance with the ethical principles originating from the Declaration of Helsinki and 
amendments and the ICH-GCP guidelines. 
12.2 
Institutional Review Board (IRB) or Independent Ethics Committee (IEC) 
This protocol, the proposed informed consent form, and other information for subjects must be 
reviewed and approved by an IRB or IEC, before the start of the trial, in compliance with local 
regulations. This committee must also approve any amendments to the protocol, other than 
administrative ones, before initiation of the amendment procedures. 
12.3 
Subject Information and Consent 
Before participation in the trial, each subject or guardian is required to provide written consent to 
participate in the trial. No trial-specific procedures will be performed before a subject’s informed 
consent is obtained.  
12.4 
Disclosure and Confidentiality 
12.4.1 
Confidentiality of trial documentation 
By signing the protocol, the investigator agrees to keep all information provided by the sponsor in 
strict confidence and to request similar confidentiality from his/her staff and the IRB or IEC. Trial 
documents provided by the trial sponsor (i.e., protocols, Investigators' Brochures, eCRFs and other 
material) will be stored appropriately to ensure their confidentiality. The information provided by 
the sponsor to the investigator may not be disclosed to others without direct written authorisation 
from the sponsor, except to the extent necessary to obtain informed consent from subjects who 
wish to participate in the trial. 
12.4.2 
Privacy of individual health information  
The investigator will undertake to protect the privacy of all individually identifiable health 
information except as specifically authorised by each individual subject through the written 
informed consent. The Informed Consent document will include a request of the subject’s consent 
to release the collected data for research purposes in such a way that the individual’s identity 
remains masked. While all data records will be identified by the corresponding subject number, 
the identity of the subject will be held in confidential source documents at the trial site. All trial 
personnel with access to this information are legally bound not to disclose such information. 


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13.0 
EMERGENCY PROCEDURES 
13.1 
Emergency Unblinding (Not Applicable) 
This is an open-label trial. 
13.2 
Reporting of Serious Adverse Events and Pregnancies 
13.2.1 
Contact person(s) and number(s) 
SAEs and pregnancies must be reported immediately (i.e., not later than 24 hours after first 
knowledge). The SAE or pregnancy report should be e-mailed or faxed to UBC using the following 
e-mail or fax-number:  
Email: EUSafety@ubc.com 
Fax number:  +41 225 964 446 
 
 
13.2.2 
Reporting procedures 
Serious adverse events 
For each SAE, the investigator will complete a Serious Adverse Event Report Form and assess the 
relationship of each SAE to trial treatment. The completed form(s) should be sent electronically to 
the UBC using the SAE Reporting fax number within 24 hours of first knowledge of the SAE.  
Follow-up reports regarding the status of the SAE and the subject’s subsequent course should be 
submitted until the SAE has subsided, the condition stabilised (in the case of persistent 
impairment), the subject receives alternative therapy, or the subject dies. The form and fax 
confirmation will be retained. Contacts for reporting SAEs, pregnancies and other safety concerns 
are provided to each site.  
14.0 
INSURANCE 
MC2 has taken out appropriate insurance policies covering the subjects in the clinical trial in 
accordance with applicable laws and regulations. 
15.0 
PUBLICATION POLICY 
The clinical trial information will be posted on www.clinicaltrials.gov and in accordance with 
applicable regulations.  
All publications (e.g., manuscripts, abstracts, oral/slide presentations, book chapters) based on this 
trial must be submitted to MC2 for review, as specified in the Clinical Trial Agreement between 
the institution, investigator and MC2 or its designee. 
 
 


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16.0 
REFERENCES 
 
(1) Kurd SK, Gelfand JM. The prevalence of previously diagnosed and undiagnosed psoriasis in 
US adults: results from NHANES 2003-2004. J Am Acad Dermatol 2009;60:218-224. 
 
(2) Chandran V, Raychaudhuri SP. Geoepidemiology and environmental factors of psoriasis and 
psoriatic arthritis. J Autoimmun 2010;34:J314-J321. 
 
(3) Schafer T. Epidemiology of psoriasis. Review and the German perspective. Dermatology 
2006;212:327-337. 
 
(4) Nestle FO, Kaplan DH, Barker J. Mechanisms of Disease: Psoriasis. N Engl J Med 
2009;361:496-509. 
 
(5) Griffiths CE, Barker J. Pathogenesis and clinical features of psoriasis. Lancet 2007;370:263-
271. 
 
(6) Horn EJ, Fox KM, Patel V, Chiou CF, Dann F, Lebwohl M. Association of patient-reported 
psoriasis severity with income and employment. J Am Acad Dermatol 2007;57:963-971. 
 
(7) Dubertret L, Mrowietz U, Ranki A et al. European patient perspectives on the impact of 
psoriasis: the EUROPSO patient membership survey. Br J Dermatol 2006;155:729-736. 
 
(8) Rapp SR, Feldman S, Exum ML, Fleischer AB, Jr., Reboussin DM. Psoriasis causes as much 
disability as other major medical diseases. J Am Acad Dermatol 1999;41:401-407. 
 
(9) Boehncke WH, Boehncke S, Tobin AM, Kirby B. The 'psoriatic march': a concept of how 
severe psoriasis may drive cardiovascular comorbidity. Experimental Dermatology 2011;20:303-
307. 
 
(10) Zanni GR. Psoriasis: issues far more serious than cosmetic. Consult Pharm 2012;27:86. 
 
(11) Fleming C, Ganslandt C, Guenther L et al. Calcipotriol plus betamethasone dipropionate gel 
compared with its active components in the same vehicle and the vehicle alone in the treatment 
of psoriasis vulgaris: a randomised, parallel group, double-blind, exploratory study. Eur J 
Dermatol 2010;20:465-471. 
 
(12) Lebwohl M, Tyring S, Bukhalo M et al. Fixed Combination Aerosol Foam Calcipotriene 
0.005% (Cal) Plus Betamethasone Dipropionate 0.064% (BD) is More Efficacious than Cal or 
BD Aerosol Foam Alone for Psoriasis Vulgaris: A Randomized, Double-blind, Multicenter, 
Three-arm, Phase 2 Study. J Clin Aesthet Dermatol 2016;9:34-41. 
 
(13) Lovato P, Norsgaard H, Tokura Y, Ropke M. Calcipotriol and betamethasone dipropionate 
exert additive inhibitory effects on the cytokine expression of inflammatory dendritic cell-Th17 
cell axis in psoriasis. J Dermatol Sci 2016;81:153-164. 


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(14) Gniadecki R, Gniadecka M, Serup J. Inhibition of glucocorticoid-induced epidermal and 
dermal atrophy with KH 1060--a potent 20-epi analogue of 1,25-dihydroxyvitamin D3. Br J 
Pharmacol 1994;113:439-444. 
 
(15) Norsgaard H, Kurdykowski S, Descargues P et al. Calcipotriol counteracts betamethasone-
induced decrease in extracellular matrix components related to skin atrophy. Arch Dermatol Res 
2014;306:719-729. 
 
(16) Menter A, Korman NJ, Elmets CA et al. Guidelines of care for the management of psoriasis 
and psoriatic arthritis Section 3. Guidelines of care for the management and treatment of 
psoriasis with topical therapies. J Am Acad Dermatol 2009;60:643-659. 
 
(17) Samarasekera E, Sawyer L, Parnham J, Smith CH. Assessment and management of 
psoriasis: summary of NICE guidance. BMJ 2012;345:e6712. 
 
(18) Dauden E, Bewley A, Lambert J, Girolomoni G, Cambazard F, Reich K. Expert 
recommendations: the use of the fixed combination calcipotriol and betamethasone dipropionate 
gel for the topical treatment of psoriasis. J Eur Acad Dermatol Venereol 2014;28 Suppl 2:22-32. 
 
(19) Hendriks AG, Keijsers RR, de Jong EM, Seyger MM, van de Kerkhof PC. Efficacy and 
safety of combinations of first-line topical treatments in chronic plaque psoriasis: a systematic 
literature review. J Eur Acad Dermatol Venereol 2013;27:931-951. 
 
(20) Selby PL, Davies M, Marks JS, Mawer EB. Vitamin D intoxication causes hypercalcaemia 
by increased bone resorption which responds to pamidronate. Clin Endocrinol (Oxf) 
1995;43:531-536. 
 
(21) Bourke J, Berth-Jones J, Iqbal SJ, Hutchinson P. High-dose topical calcipotriol in the 
treatment of extensive psoriasis vulgaris. Br J Dermatol 1993;129:74-76. 
 
(22) Matkovic V, Ilich JZ, Andon MB et al. Urinary calcium, sodium, and bone mass of young 
females. Am J Clin Nutr 1995;62:417-425. 
 
(23) O'Brien KO, Abrams SA, Stuff JE, Liang LK, Welch TR. Variables related to urinary 
calcium excretion in young girls. J Pediatr Gastroenterol Nutr 1996;23:8-12. 
 
(24) Carroll C, Feldman S, Camacho FT, Balkrishnan R. Better medication adherence results in 
greater improvement in severity of psoriasis. Br J Dermatol 2004;151:895-897. 
 
(25) Amphastar Pharmaceuticals I.  CortrosynTM US Prescribing Information.  2005.  
 
(26) MC2 Therapeutics. Investigational Brochure, version 3, 2017.  2017.  
 
(27) FDA. Taclonex® Ointment Prescribing Information.  2017. 
 


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


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17.2 
Appendix 2 
Vendors  
 
Novella Clinical, a Quintiles Company, 365 W. Passaic St, Suite 550, Rochelle Park, NJ 07662, 
United States. Novella Clinical will be responsible for all services related protocol writing and 
the conduct of the trial, as specified in the contract. 
 
ACM Global Central Laboratory, 160 Elmgrove Park Rochester, New York. ACM will be 
responsible for all services related to central laboratory analysis, as specified in the contract. 
 
Clinical Materials Services Unit (CMSU), 77 Ridgeland Rd. Rochester, NY, United States.  
CMSU will be responsible for all services related to packaging, labeling, distribution and 
destruction of the investigational medical products, as specified in the contract. 
 
United BioSource Corporation (UBC), Chemin des Coquelicots 16, CH-1214 Vernier Geneva, 
Switzerland. UBC will be responsible for services related to SAE reporting and tracking, as 
specified in the contract. 
  
DSG Inc, 325 Technology Drive, Malvern, Pennsylvania 19355, United States. DSG will be 
responsible for providing electronic data capture and IWRS services as specified in the contract. 
 
BioTelemetry Research, One Preserve Parkway, Suite 600, Rockville, Maryland 20852, United 
States. BioTelemetry Research will be responsible for the ECG services as specified in the 
contract. 
 
ICON Laboratory Services Inc., 8282 Halsey Road, Whitesboro, NY 13492 USA. ICON will be 
responsible for the PK analysis. 
 
 
 
 
 
 
 
 
 
 
 
 






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

SAP_001.pdf: 
MC2 Therapeutics  
Page 1 of 84 
Protocol No. MC2-01-C3 
September 21, 2018 
Novella No. NYA14539 
 
Protocol No. MC2-01-C3 
Novella Study No. NYA14539 
 
STATISTICAL ANALYSIS PLAN 
 
A Randomised, Multicentre, Open-label, Parallel-group Maximal Use Trial, Evaluating the 
Pharmacokinetic Profile of the Active Ingredients and their Metabolites after Application 
of MC2-01 Cream Compared with Active Comparator in Subjects with Extensive Psoriasis 
Vulgaris 
 
Novella Clinical 
365 West Passaic Street 
Rochelle Park, NJ 07662, USA 
 
21 September 2018 
Version No. Amendment 1.0 
   
Johan Selmer, MD 
VP Medical Affairs 
MC2 Therapeutics 
 
 
 
  
    Carol Udell, MS 
Sr. Director, Clinical Reporting 
Novella Clinical 
 
  
 
21-Sep-2018 | 12:15:46 EDT
21-sep-2018 | 11:43:37 EDT


MC2 Therapeutics  
Page 2 of 84 
Protocol No. MC2-01-C3 
September 21, 2018 
Novella No. NYA14539 
Table of Contents 
1. 
INTRODUCTION ..................................................................................................................5 
2. 
STUDY OBJECTIVES ..........................................................................................................5 
3. 
STUDY DESIGN ....................................................................................................................5 
4. 
HARDWARE AND SOFTWARE ........................................................................................6 
5. 
DATABASE CLOSURE .......................................................................................................7 
6. 
SAMPLE SIZE DETERMINATION ...................................................................................7 
7. 
HANDLING OF MISSING DATA ......................................................................................7 
8. 
ANALYSIS POPULATIONS ...............................................................................................7 
9. 
DATA CONVENTIONS FOR ANALYSIS .........................................................................8 
9.1 General Statistical Principles ..........................................................................................8 
9.2 Study Day and Baseline ...................................................................................................8 
10. STATISTICAL EVALUATION ...........................................................................................8 
10.1 Subject Disposition.......................................................................................................8 
10.2 Protocol Deviation ........................................................................................................8 
10.3 Demographic and Baseline Characteristics ...............................................................9 
10.4 Study Drug Exposure and Accountability .................................................................9 
10.5 Prior and Concomitant Medications ........................................................................10 
10.6 Concurrent Procedures .............................................................................................10 
10.7 Medical History ..........................................................................................................10 
10.8 Safety Analysis ...........................................................................................................10 
10.8.1 Safety Endpoints ........................................................................................................10 
10.8.2 Analyses of Safety Endpoints ....................................................................................11 
10.8.2.1 
HPA-axis Suppression ...................................................................................11 
10.8.2.2 
Calcium Metabolism Endpoints ...................................................................12 
10.8.2.3 
Adverse Events ...............................................................................................12 
10.8.2.5 
Safety Laboratory Parameters .....................................................................13 
10.8.2.6 
Vital Signs .......................................................................................................14 
10.8.2.7 
Electrocardiograms (ECG) ...........................................................................14 
10.8.3 Physical Examination (PE)........................................................................................14 
10.9 Pharmacokinetics Analysis .......................................................................................14 
10.9.1 Analysis of Pharmacokinetic Parameters ................................................................14 


MC2 Therapeutics  
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10.10 Analysis of Other Endpoints .....................................................................................16 
10.10.1 
Physician Global Assessment of Psoriasis Severity (PGA) ........................16 
10.10.2 
Body Surface Area Involvement of Psoriasis (BSA) ...................................16 
10.10.3 
Psoriasis Treatment Convenience Scale (PTCS) ........................................16 
11. CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES .........................16 
12. HEADINGS ..........................................................................................................................18 
13. ARCHIVING AND RETENTION OF DOCUMENTS ....................................................18 
14. OUTLINE OF PROPOSED TABLES, FIGURES AND LISTINGS ..............................19 
 
 


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List of Abbreviations and Definitions of Terms 
Abbreviation 
Definition 
ACTH 
Adrenocorticotropic hormone  
AE 
Adverse event 
ALP 
Alkaline phosphatase 
AUC0-7 
Area under the time-concentration curve from time zero to 7 hours 
AUC0-t 
Area under the time-concentration curve from time zero to the last 
measurable concentration 
AUC0-∞ 
Area under the time-concentration curve from time zero to infinity 
BDP 
Betamethasone dipropionate 
BSA 
Body surface area 
CAL 
Calcipotriene (United States term) / Calcipotriol (European Union term) 
Cmax 
Maximum plasma drug concentration 
CRO 
Contract Research Organisation 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
HPA 
Hypothalamic-pituitary-adrenal 
ICF 
Informed consent form 
IP 
Investigational product 
IRB 
Institutional Review Board 
IWR 
Interactive web response  
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
OTC 
Over the counter 
PGA 
Physician’s Global Assessment 
PK 
Pharmacokinetics 
PTH 
Parathyroid hormone 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SD 
Standard deviation 
SOP 
Standard operating procedure 
T1/2 
Elimination half-life 
Tmax 
Time to maximum plasma drug concentration 
UPT 
Urine pregnancy test 
US  
United States 
WBC 
White blood cell 


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1. INTRODUCTION 
This Statistical Analysis Plan (SAP) is based on the study Protocol version 3.0 dated December 
20, 2017.   
This document provides additional details concerning the statistical analyses outlined in the 
protocol and reflects any changes to the protocol from any amendments. This plan will not repeat 
all the definitions given in the protocol but will provide further details of the summaries and 
analyses planned therein.     
2. STUDY OBJECTIVES 
The primary objective is to evaluate the pharmacokinetic profile of the active ingredients and their 
main metabolites after application of MC2-01 cream, and compare with the active comparator 
following once daily topical application under maximum-use conditions in subjects with extensive 
psoriasis vulgaris.  
The secondary objective is to evaluate the effect of MC2-01 cream on the hypothalamic-pituitary-
adrenal (HPA) axis and calcium metabolism following once daily topical application under 
maximum-use conditions in subjects with extensive psoriasis vulgaris. 
3. STUDY DESIGN 
This is a Phase 2, randomised, open-label, parallel-group, multicentre trial in which the 
investigational product, MC2-01 cream, and CAL/BDP ointment (comparator) are investigated in 
subjects with clinically diagnosed extensive psoriasis vulgaris of disease severity assessed by 
Physician’s Global Assessment (PGA) of at least moderate (Figure 1). Subjects who meet 
inclusion/exclusion criteria will be randomly assigned in a 1:1 ratio to receive either MC2-01 
cream or the comparator. Subjects assigned to MC2-01 cream will apply 1 dose of trial medication 
topically once daily for 8 weeks and the subjects assigned to the comparator will apply 1 dose of 
trial medication topically once daily for 4 weeks. 
At Week 4, the pharmacokinetic (PK) profile of calcipotriene (CAL), betamethasone dipropionate 
(BDP) and their main metabolites MC1080 and betamethasone 17-propionate, respectively, will 
be assessed for both treatment groups. At Week 8, the PK profile of CAL, BDP and their main 
metabolites will be assessed for the MC2-01 cream treatment group only. At Week 4 and Week 8, 
the effect of once-daily use of MC2-01 cream on the HPA axis and calcium metabolism will be 
evaluated for MC2-01 cream treatment group. Other safety assessments (local skin reactions, AEs, 
laboratory tests, electrocardiogram (ECG)), vital signs and physical examinations) and efficacy 
assessments are also performed. 
 
 


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Figure 1: Study Design 
 
  
4. HARDWARE AND SOFTWARE 
Statistical analysis will be performed following Novella Clinical standard operating procedures 
(SOP) and on the Novella Clinical computer network. All statistical analysis will be performed 
using SAS Version 9.3 or higher with program code prepared specifically for the project by 
qualified Novella Clinical statisticians and SAS programmers. 
The SAS programs will generate rich-text-formatted (RTF) output with the “RTF” extension using 
the SAS Output Delivery System (ODS). The summary tables and listings will be formatted using 
the Times New Roman 9-point font. The RTF output is included in report documents prepared 
with Microsoft Word and converted to PDF format without typographical change. 
Study data tabulation model (SDTM) data sets and analysis data model (ADaM) data sets will be 
created and taken as input to validated SAS programs to generate the report-ready tables, listings, 


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and figures. Each output display will show the names of the data sets and SAS program used to 
produce it.   
5. DATABASE CLOSURE 
After completion of all data review procedures, validation of the project database, and approval of 
the data review document by the study sponsor, the clinical database will be closed. Any change 
to the clinical database after this time will require written authorization, with explanation, by the 
Sponsor and the Biostatistician. 
6. SAMPLE SIZE DETERMINATION 
The choice of sample size in this trial is not based on statistical considerations, but rather on 
regulatory considerations with respect to common practice in maximum use studies evaluating 
pharmacokinetic profiles and evidence of HPA safety. The chosen number of approximately 25 
subjects included in the PK population at Week 4 in each treatment arm is considered sufficient to 
compare the PK properties corresponding to the two treatments. 
7. HANDLING OF MISSING DATA  
No imputation will be made for missing data. 
8. ANALYSIS POPULATIONS 
Three analysis populations will be defined for analysis: 
• Safety Population: will include all randomized subjects who have been dispensed the 
trial medication, excluding subjects who return all of the trial medication unopened. The 
Safety Population will be used for all safety analyses other than evaluation of the HPA-
axis. 
• HPA population: will include all subjects in the Safety population that are assigned to 
MC2-01 cream and who show normal HPA function at Baseline (defined as a 30-minute 
post-stimulation cortisol level ≥18 μg/dL). Since the objective of the analysis is to estimate 
the risk to subjects with normal HPA function of HPA-axis suppression following 
treatment, subjects who meet the definition of HPA-axis suppression at Baseline will be 
excluded from the analysis. The HPA population will be used for the HPA axis suppression 
analysis. 
• Pharmacokinetic (PK) Population: will include all subjects in the Safety population who 
have received the planned application of treatment at the Week 4 or Week 8 visit, 
respectively, and have had at least one post-application blood draw for PK assessment 
at the corresponding visit. The PK Population will be used for the PK analysis. 


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All safety, HPA and PK analyses will be conducted according to the treatment actually received.  
9. DATA CONVENTIONS FOR ANALYSIS 
9.1 General Statistical Principles 
All statistical processing will be performed using the SAS system (Version 9.3 or higher).  
All observed and derived variables (e.g., change from baseline) used in the summaries of analyses 
will be presented in by-subject listings. Descriptive statistics will be used to provide an overview 
of the safety and PK results. For categorical parameters, the number and percentage of subjects in 
each category will be presented. The denominator for percentage will be based on the number of 
subjects appropriate for the purpose of analysis. For continuous parameters, descriptive statistics 
will include number of observations, mean, standard deviation (SD), median, and range. The PK 
parameters will be summarised using appropriate descriptive statistics including median, lower 
and upper quartiles, minimum and maximum. Geometric means and coefficient of variation (CV) 
will be provided as appropriate.  
It is planned that the data from all centers that participate in this protocol will be combined so that 
an adequate number of subjects will be available for analysis. 
No interim analyses are planned.  
9.2 Study Day and Baseline 
For purpose of the SAP, Day 1 is defined as the date of first application of study drug, which 
corresponds to Randomization/Visit 1 of the study protocol. Study day is calculated relative to the 
date of Day 1. 
Baseline is defined as the last available measurement prior to first application of study drug. 
Change from baseline is defined as the post-baseline value minus the baseline value.  
10. STATISTICAL EVALUATION  
10.1 
Subject Disposition 
The number and percentage of subjects who are screened, randomized, included in each analysis 
population, who complete the study, and withdraw from the study (overall and by reason for 
withdrawal) will be summarized, overall and by treatment group.  
A by-subject enrolment and disposition listing will be presented for all randomized subjects.  
10.2 
Protocol Deviation 
Protocol deviations will be presented in a by-subject listing. 


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10.3 
Demographic and Baseline Characteristics 
Demographics, baseline characteristics will be summarized overall and by treatment for the Safety, 
HPA and PK populations. The following demographic and baseline variables will be included: 
• Age (years) 
• Gender 
• Race  
• Ethnicity  
• Fitzpatrick Skin Type 
• Weight (kg) 
• Height (cm) 
• Baseline HPA Axis Suppression Status (MC2-01 cream group only) 
• Baseline PGA 
• Baseline Total BSA (%) 
• Duration of psoriasis in years (calculated as year of baseline minus year of first psoriasis 
diagnosis) 
10.4 
Study Drug Exposure and Accountability  
Subjects will record the date of each trial medication application in the subject diary. The kit 
number, and corresponding date dispensed and returned will be collected.  
The weight of the returned kits will also be collected.   
The following parameters of study medication exposure will be summarized by treatment group 
and by study period, i.e., from day 1 to Week 4 (both groups) and from day 1 to Week 8 (MC2-01 
cream group), for the Safety Population: 
 
• Total number of days of exposure to the study drug, defined as the date of last application 
of study drug during the period minus date of first application plus one. The last application 
is the in-clinic dosing at Week 4 visit (Day 1 to Week 4 period) and Week 8 visit (Day 1 
to Week 8 period).  
• Total number of missed doses during each study period per subject diary 
• Total number of applications during each study period, defined as the total number of doses 
required minus total number of doses missed. Total number of required doses is defined as 
total number of days of exposure minus any days of investigator approved stop (if 
applicable) 
• Total weight of trial medication used (g) during each study period, defined as the 
summation of amount of drug used for all dispensed kits. Amount of drug used per kit is 
defined as the difference in weight between the returned and dispensed kits, where weight 


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of dispensed kits is a unit value. Amount of drug used for sealed and unreturned kits will 
be assumed to be 0.0 g 
• Amount of drug used per week (g/per week), defined as the total amount of drug used 
divided by total number of days of exposure to the study drug multiplied by 7 
10.5 
Prior and Concomitant Medications 
Prior (with stop dates prior to Day 1) and concomitant medications (ongoing or with stop dates on 
or after Day 1) for all randomised subjects will be provided in a by-subject listing. Concomitant 
medications will be summarized by WHO-DDE Anatomical-Therapeutic-Chemical (ATC) 
classification and preferred term (PT) for each treatment for Safety population. 
For the determination of prior vs. concomitant medications, the following rules regarding the stop 
date will be applied: 
• If only year was recorded, and it is before Day 1, it is a prior medication; if year is same or 
after Day 1, it is assumed to be a concomitant medication. 
• If day is missing, but month and year are before Day 1, it is a prior medication; if month 
and year are the same or after Day 1, it is assumed to be a concomitant medication. 
• If start date is after Day 1, it is a concomitant medication regardless. 
Psoriasis treatment history will be displayed in a by-subject listing. 
10.6 
Concurrent Procedures 
All concurrent procedures will be provided in a by subject listing for all randomized subjects. 
10.7 
Medical History 
Past and current medical conditions will be coded using MedDRA dictionary (version 20.0). 
Medical history for all randomized subjects will be provided in a by-subject listing. 
10.8 
Safety Analysis 
10.8.1 Safety Endpoints 
Primary safety endpoints include: 
• HPA-axis suppression 
HPA-axis function will be assessed in a challenge test with an intravenous dose of   
adrenocorticotropic hormone (ACTH) (Cosyntropin). Normal HPA function is, based on 
the Cosyntropin US Packing Insert (USPI) (revision May 2018), defined as a 30-minute 
post-stimulation cortisol level ≥18 μg/dL. 
 


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Conversely, HPA-axis suppression is defined as 30-minute post-stimulation cortisol level 
<18 μg/dL.  
 
HPA-axis function status will be considered as missing if post-stimulation serum cortisol 
level is missing. 
• Changes in calcium metabolism endpoints from 24-hour urinalysis, including 
o Albumin-corrected serum calcium 
o 24 hours urinary calcium excretion 
o Ratio of urinary calcium to creatinine 
Other safety endpoints include: 
• Adverse events (AEs) 
• Local Skin Reaction  (LSR) Assessment 
o Investigator assessed signs: erythema, scaling, edema, atrophy, vesicles and 
erosion/ulceration; vesicles, and erosion/ulceration 
o Subject assessed symptoms: burning or pain 
• Laboratory parameters 
o Hematology: hemoglobin, hematocrit, red blood cell (RBC) count, mean 
corpuscular volume (MCV), white blood cell (WBC) count, including 
differential count and platelet count. 
o Serum biochemistry: cortisol, urea, glucose, creatinine, calcium, albumin, 
calcium (albumin corrected), sodium, potassium, chloride, calcium, phosphate, 
alkaline phosphatase (ALP), plasma parathyroid hormone (PTH), 25-OH 
Vitamin D (Visit 1 only) 
o 24-hour urinalysis: calcium, phosphate, creatinine, volume, total calcium 
excretion, total phosphate excretion, total creatinine excretion, urinary 
calcium:creatinine ratio, urinary phosphate:creatinine ratio 
• Vital signs (blood pressure, pulse rate) 
• Standard 12-lead electrocardiogram (ECG) (MC2-01 cream subjects only) 
• Physical examination (PE) 
10.8.2 Analyses of Safety Endpoints 
10.8.2.1 HPA-axis Suppression  
The number and proportion of subjects with HPA-axis suppression at Week 4 will be summarised 
for the HPA population. Subjects with HPA-axis suppression at Week 4, was as described in the 


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protocol, contacted to discontinue use of MC2-01 cream. Subjects with HPA-axis suppression at 
Week 8 will be summarised overall and separately by HPA-axis suppression status at Week 4.  
An additional analysis of the number and proportion of subjects with HPA-axis suppression will 
be summarised based on the test laboratory normal reference range established for the analytical 
method used by the test laboratory in the trial for the ACTH challenge test. 
• In this analysis HPA suppression is defined as a 30-minute post-stimulation cortisol level 
< 14 µg/dl (test laboratory normal reference range of 14 to 36 µg/dl for the 30-minute post-
stimulation cortisol level). This analysis will be performed among MC2-01 cream subjects 
whose Baseline cortisol level is ≥ 14 µg/dl 
All HPA-axis function test results (baseline, Week 4, Week 8, and Follow-up) will be presented 
in a by-subject listing for the Safety population. 
10.8.2.2 Calcium Metabolism Endpoints  
All calcium metabolism data will be presented in a by-subject listing for the following parameters: 
• Albumin-corrected serum calcium 
• 24 hours urinary calcium excretion 
• Ratio of urinary calcium to creatinine 
Observed values and changes from baseline to Week 4 and Week 8 will be summarized using 
descriptive statistics for subjects in the Safety population assigned to MC2-01 cream.                         
10.8.2.3 Adverse Events 
AE terms will be coded using MedDRA dictionary (version 20.0). A treatment-emergent AE 
(TEAE) is defined as an AE with a start date on or after the first application to trial medication 
(Day 1). If relationship to study medication is missing, the event will be conservatively 
summarized as being related to study drug. If intensity is missing, a separate category of missing 
intensity will be included in the summary table, and no imputation of severity will be performed. 
Through the data cleaning process, all attempts will be made to avoid missing values for 
relationship and severity. 
All AEs will be presented in a by-subject listing, detailing the verbatim term given by the 
investigator, the PT, SOC, whether or not related to Cosyntropin or study procedure, location of 
AE to treatment area, start date, stop date, intensity, outcome, relationship to study medication 
(definitely, probably, possibly, and not related), action taken with study medication, action taken 
to treat the AE, seriousness and criteria for seriousness. For subjects assigned to MC2-01 cream, 
all TEAEs will be assigned to the Week 1-4 (starting from Day 1 to 28) or post-Week 4 period 
(starting from Day 29 and after) based on onset dates. Serious AEs and AEs leading to study drug 
discontinuation will be presented in a separate listing.  


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An overall summary of AEs will be presented by treatment and by period (MC2-01 group only). 
The summary will include the total number of events, frequency counts and percentages with: 
• Any AE 
• Any TEAE 
• Any serious TEAE 
• Any treatment-related TEAE  
• Any TEAE leading to study drug discontinuation 
Summaries of the incidence of TEAEs will be displayed by treatment and by period (MC2-01 
group only) according to the following: 
• All TEAEs by PT in descending order of frequency (the combined frequency of both 
treatments) 
• All TEAEs by SOC, PT, and maximum severity (mild, moderate, or severe) 
• All TEAEs by SOC, PT, and maximum relationship (recorded as 'definitely', 'probably', 
and 'possibly') to the study drug 
At each level of summarization, a subject will be counted once if he/she reported one or more 
events. The severity of TEAEs and relationship to study drug will be summarized in a similar 
manner. For summaries of relationship to study drug, a subject will be classified according to the 
closest relationship. For summaries of TEAE severity, a subject will be classified according to the 
highest severity.  
10.8.2.4 
Local Skin Reaction (LSR) Assessment 
LSR assessments by investigator and subject will be summarized using frequency counts and 
percentages by treatment and visit. By-subject listings will be provided. 
10.8.2.5 Safety Laboratory Parameters 
Clinical laboratory (hematology, biochemistry and urinalysis) results will be presented in by-
subject listings. Abnormal laboratory findings will be flagged and presented in a separate listing.  
Absolute values, changes from baseline, and relative changes from baseline (defined as ratio of 
the post-baseline vs baseline value) will be summarized using descriptive statistics (means, 
medians, standard deviations, ranges, and coefficient of variations) by treatment and by visit. Shift 
tables using extended normal ranges (baseline to Week 4 and most extreme post-baseline value up 
to Week 4 for both arms) will also be provided.  
Urine pregnancy test will be presented in a by-subject listing for subjects with childbearing 
potential.             


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10.8.2.6  Vital Signs 
Vital signs data will be presented in a by-subject listing. Observed values and changes from 
baseline will be summarized using descriptive statistics by treatment and visit.  
10.8.2.7  Electrocardiograms (ECG) 
ECG data will be presented in a by-subject listing, with flagging of abnormal results.         
10.8.3  Physical Examination (PE) 
Physical examination results will be present in a by-subject listing.  
10.9 
Pharmacokinetics Analysis 
All analyses of pharmacokinetics (PK) will be based on the PK population. 
All available concentration results will be summarised using appropriate descriptive statistics 
(number of subjects, number of quantifiable concentrations, median, lower and upper quartiles, 
minimum, maximum) for active ingredients (BDP and CAL) and for their major metabolites. A 
listing for sample date/times as well as derived sampling time deviations will be provided. Median 
and individual concentration versus time curves will be plotted (linear and semi-log plots). 
Nominal sample collection times will be used in determining concentration descriptive statistics 
and plotting median concentration versus time profiles. 
All analyte concentrations below the lower limit of quantification (BLOQ) will be reported as the 
lower limit of quantification (LLoQ) and will be treated as LLoQ in descriptive statistics and 
plasma concentration-time profiles.  
10.9.1 Analysis of Pharmacokinetic Parameters 
Plasma PK parameters shown below (AUC0-t, AUC0-∞, AUC0-7, Cmax, Tmax, and T½) will be 
calculated at Week 4 in subjects randomized to comparator and MC2-01 groups and Week 8 in 
subjects randomized to MC2-01 cream only.  
For a given analyte, the PK parameters AUC0-t, AUC0-∞, Tmax, and T½ will be calculated if data 
allow. AUC0-7 and Cmax will be calculated using standard formulas inserting the lower limit of 
quantification (LLoQ) for non-quantifiable levels of the analyte; therefore, AUC0-7 will be an 
upper limit in case at least one time point shows a non-quantifiable level of the analyte, and Cmax 
will be an upper limit in case all time points show non-quantifiable levels of the analyte.  
Cmax 
Maximum plasma drug concentration. BLOQ Concentrations will be 
treated as LLoQ for this calculation 


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Tmax 
Time to maximum plasma drug concentration. If the maximum 
concentration value occurs at more than one time point, Tmax is defined as 
the first time point with this value 
AUC0-7 
Area under the time-concentration curve from time zero to 7 hours, as 
calculated by the linear trapezoidal method. BLOQ Concentrations will be 
treated as LLoQ for this calculation 
AUC0-t 
Area under the time-concentration curve from time zero to the last 
quantifiable concentration  
AUC0-∞ 
Area under the time-concentration curve from time zero to infinity, 
calculated as AUC0-t + Ctf/λz, where Ctf is the last concentration ≥ LoQ. 
AUC0-∞ will be calculated only if λz can be calculated. 
T½ 
Elimination half-life, calculated as ln(2)/ λz. T½ will not be calculated if 
λz cannot be determined 
Λz 
Elimination (terminal phase) rate constant, calculated as the slope of the 
terminal phase linear regression line of the log-scale concentration over 
the time points corresponding to the elimination phase of the 
concentration-time profiles. The elimination rate constant, λz, will not be 
calculated if the elimination phase of the log-linear concentration-time 
profile cannot be fit with an appropriate regression line. The time points 
corresponding to a subject’s elimination phase will be identified by 
visually examining the log-scale concentration-time profile. A minimum 
of three points, not including Cmax, in which there is a relatively straight 
downward trend in concentration when plotted on a log scale, and the 
adjusted R2 value for the fitted line must be at least 0.9 is required for the 
determination of λz. As an additional confirmation of the suitability of 
λz, the log-linear profile, which includes the regression line through the 
terminal points, will be checked via visual inspection, to determine 
whether the regression appropriately represents the terminal slope. 
 
PK parameters will be listed and summarized using descriptive statistics (n, median, lower and 
upper quartiles, minimum and maximum) where appropriate. Geometric means and geometric CV 
will be calculated for AUC0-t, AUC0-∞, AUC0-7, and Cmax as appropriate. An exception to this is Tmax 
and T½ where only median, minimum, and maximum will be presented. 
Assessment of systemic exposure (Week 4) 


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Assessment of relative systemic exposure in the two treatment arms will be performed for AUC0-
7 and Cmax at Week 4. If any of the post-dose time point shows a non quantifiable level of the 
analyte, the calculated PK parameters will be considered left censored. In particular, AUC0-7 will 
be considered censored if at least one post-dose concentration is below LLOQ. Cmax will be 
considered censored if all post-dose values are below LLOQ. To account for the censored data, the 
SAS PROC LIFEREG procedure will be used on log-transformed PK parameters with treatment 
group as a fixed effect. Geometric mean ratio and associated 90% confidence interval (CI) (back-
transformed from the estimates) will be presented. 
10.10 Analysis of Other Endpoints  
10.10.1Physician Global Assessment of Psoriasis Severity (PGA) 
PGA will be summarised using frequency counts and percentages for each treatment at Week 4 
(all subjects) and at Week 8 (subjects assigned to MC2-01 cream). The proportion of subjects with 
treatment success, defined as a minimum 2-point decrease from Baseline in the PGA will also be 
summarized.  
10.10.2Body Surface Area Involvement of Psoriasis (BSA) 
BSA results will be presented in a by-subject listing.  
10.10.3Psoriasis Treatment Convenience Scale (PTCS) 
The PTCS consists of 6 disease-specific, self-report questions with a recall period of 1 week and 
rated on a 1-10 scale. 
1. How easy was the treatment to apply to the skin? 
2. How greasy was the treatment when applying it to the skin? 
3. How moisturised did your skin feel after applying the treatment? 
4. How greasy did your skin feel after applying the treatment? 
5. How much did treating your skin disrupt your daily routine? 
6. Overall, how satisfied were you with the medical treatment? 
Each of the questions and the sum of the first 5 questions of PTCS will be summarized using 
descriptive statistics by treatment for Week 4. Sum of the first 5 question will be further compared 
between MC2-01 cream and the active comparator using a mixed effect model with treatment as a 
systematic effect and study site as a random effect. Treatment difference (MC2-01 cream minus 
active comparator) along with 95% CI will be reported.  
11.  CHANGES FROM THE PROTOCOL AND PLANNED ANALYSES 
The 30 minutes ACTH  test using the ACTH analogue tetracosactide to stimulate cortisol secretion 
from the adrenals is an effective test for the assessment of the HPA axis in subjects with pituitary 


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disease. Diagnostic criteria for adrenal insufficiency have traditionally relied both on the absolute 
level of cortisol 30 minutes after injection of tetracosactide as well as a requirement of an absolute 
increase in cortisol during the test. The diagnostic criteria used in the MC2-01-C3 protocol was 
based on the USPI dated  February 2012 (1) for Cosyntropin in which there were specific 
requirements to plasma cortisol both concerning the level of increase as well as the 30 minutes 
value according to the original description of the test (2) when testing morning samples. The 
diagnostic value of an absolute increase in cortisol has, however, been challenged. Several studies, 
e.g.(3, 4) have shown that calculation of the increment cortisol increase is of no diagnostic value, 
and careful reviews (5, 6) have strongly warned against this parameter as a diagnostic criterion. 
As a consequence, both expert guidelines from the Endocrine Society (7)  as well as the recently 
updated (May 2018) USPI for Cosyntropin  (8) recommends the 30 minutes cortisol value as the 
sole diagnostic criterion for the diagnosis of adrenal insufficiency  with a limit for adrenal 
supression of  plasma cortisol < 18 μg/dl (500 nmol). This criterion  is used in the  evaluation of 
the data obtained in MC2-01-C3 trial. Furthermore, the plasma cortisol from the ACTH challenge 
test is measure by mass spectrometry. Mass spectrometry assays of cortisols are without any of the 
positive bias that plaque most cortisol immunoassays (9)  and consequently limit for adrenal 
supression of  plasma cortisol is below 14 μg/dl (390 nmol/l)  according to laboratory report from 
the manufacturer (Quest Diagnostics) of this test. For this reason, this lower limit for plasma 
cortisol of 14 μg/dl (390 nmol/l)  will also be used in the evaluation of the data obtained in MC2-
01-C3 trial. 
 
1. 
FDA. Cosyntropin USPI Sandoz. 2012. 
2. 
Wood JB, Frankland AW, James VH, Landon J. A rapid test of adrenocortical function. 
Lancet. 1965;1(7379):243-5. 
3. 
Patel SR, Selby C, Jeffcoate WJ. The short Synacthen test in acute hospital admissions. 
Clin Endocrinol (Oxf). 1991;35(3):259-61. 
4. 
Widmer IE, Puder JJ, Konig C, Pargger H, Zerkowski HR, Girard J, et al. Cortisol 
response in relation to the severity of stress and illness. J Clin Endocrinol Metab. 
2005;90(8):4579-86. 
5. 
Clark PM, Neylon I, Raggatt PR, Sheppard MC, Stewart PM. Defining the normal 
cortisol response to the short Synacthen test: implications for the investigation of hypothalamic-
pituitary disorders. Clin Endocrinol (Oxf). 1998;49(3):287-92. 
6. 
Arafah BM. Hypothalamic pituitary adrenal function during critical illness: limitations of 
current assessment methods. J Clin Endocrinol Metab. 2006;91(10):3725-45. 
7. 
Bornstein SR, Allolio B, Arlt W, Barthel A, Don-Wauchope A, Hammer GD, et al. 
Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical 
Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-89. 


MC2 Therapeutics  
Page 18 of 84 
Protocol No. MC2-01-C3 
September 21, 2018 
Novella No. NYA14539 
8. 
FDA. Cosyntropin USPI Sandoz. May 2018. 
9. 
El-Farhan N, Pickett A, Ducroq D, Bailey C, Mitchem K, Morgan N, et al. Method-
specific serum cortisol responses to the adrenocorticotrophin test: comparison of   and five 
automated immunoassays. Clin Endocrinol (Oxf). 2013;78(5):673-80. 
 
12. HEADINGS 
Each page of the analysis will show the sponsor’s name, the investigational product, and the 
protocol number. Report tables will be embedded in the MS Word report document from SAS 
program output without change. The footer of each table will show the name of the SAS program 
module which generated it, the names of all data sets providing input data in the program and the 
date and time the table was generated. 
13. ARCHIVING AND RETENTION OF DOCUMENTS 
After finalization of the analysis, the following will be archived at Novella Clinical and/or with 
the study sponsor: 
• SAP and any amendments 
• All SAS code used in the project for statistical analysis, report tables generation, and 
analysis data set creation 
• Tables, listings and figures as included in the clinical study report 
• SAS study data tabulation model (SDTM) and analysis dataset model (ADaM) datasets 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 19 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
14. 
OUTLINE OF PROPOSED TABLES, FIGURES AND LISTINGS 
 
Summary Tables 
14.1 
Summary of Disposition, Demographic, and Exposure Tables 
14.1.1.1 
Summary of Subject Disposition 
14.1.2.1 
Summary of Subject Demographics and Baseline Characteristics; Safety Population  
14.1.2.2 
Summary of Subject Demographics and Baseline Characteristics; HPA Population 
14.1.2.3 
Summary of Subject Demographics and Baseline Characteristics; PK Population 
14.1.3 
Summary of Extent of Exposure and Compliance; Safety Population 
14.1.4 
Summary of Concomitant Medications by Anatomical Therapeutic Chemical Class (ATC) and Preferred Term; Safety Population 
 
 
14.2 
Summary of Study Endpoints Tables 
14.2.1.1 
Summary of Plasma Concentration of CAL (ng/mL) by Time Point; PK Population 
14.2.1.2 
Summary of Plasma Concentration of BDP (ng/mL) by Time Point; PK Population 
14.2.1.3 
Summary of Plasma Concentration of MC1080 (ng/mL) by Time Point; PK Population 
14.2.1.4 
Summary of Plasma Concentration of Betamethasone 17-propionate (ng/mL) by Time Point; PK Population 
14.2.2.1 
Summary of Plasma Concentration of CAL (ng/mL) Pharmacokinetics Parameters; PK Population 
14.2.2.2 
Summary of Plasma Concentration of BDP (ng/mL) Pharmacokinetics Parameters; PK Population 
14.2.2.3 
Summary of Plasma Concentration of MC1080 (ng/mL) Pharmacokinetics Parameters; PK Population 
14.2.2.4 
Summary of Plasma Concentration of Betamethasone 17-propionate (ng/mL) Pharmacokinetics Parameters; PK Population 
14.2.3.1 
Assessment of Relative Systemic Exposure of CAL(ng/mL) at Week 4; PK Population 
14.2.3.2 
Assessment of Relative Systemic Exposure of BDP (ng/mL) at Week 4; PK Population 
14.2.3.3 
Assessment of Relative Systemic Exposure of MC1080 (ng/mL) at Week 4; PK Population 
14.2.3.4 
Assessment of Relative Systemic Exposure of Betamethasone 17-propionate (ng/mL) at Week 4; PK Population 
14.2.4.1 
Summary of HPA-Axis Suppression (Based on Cosyntropin US Packing Insert); HPA Population  
14.2.4.2 
Summary of HPA-Axis Suppression (Based on Lab Reference Range); MC2-01 Cream Subjects with Baseline Cortisol Level ≥ 14 µg/dl 
14.2.5 
Summary of Calcium Metabolism; HPA Population 
14.2.6 
Summary of Physician’s Global Assessment (PGA); Safety Population 
14.2.7 
Summary of Psoriasis Treatment Convenience Score (PTCS) at Week 4; Safety Population 
 
 
14.3 
Summary of Safety Tables 
14.3.1.1 
Overall Summary of Adverse Events; Safety Population 
14.3.1.2 
Summary of Treatment-emergent Adverse Events, Weeks 1-4 by System Organ Class and Preferred Term in Descending Frequency; Safety Population 
14.3.1.3 
Summary of Treatment-emergent Adverse Events, Weeks 1-4 by System Organ Class, Preferred Term, and Maximum Severity; Safety Population 
14.3.1.4 
Summary of Treatment-emergent Adverse Events, Weeks 1-4 by System Organ Class, Preferred Term, and Maximum Causality; Safety Population 
14.3.2.1.1 
Summary of Clinical Laboratory Results by Treatment and Visit, Biochemistry; Safety Population 
14.3.2.1.2 
Summary of Clinical Laboratory Results by Treatment and Visit, Hematology; Safety Population 
14.3.2.2.1 
Clinical Laboratory Results, Shifts from Baseline, Biochemistry; Safety Population 
14.3.2.2.2 
Clinical Laboratory Results, Shifts from Baseline, Hematology; Safety Population 
14.3.3 
Summary of Vital Signs by Treatment and Visit; Safety Population 
14.3.4 
Summary of Investigator Assessed Local Skin Reactions (LSR); Safety Population 


MC2 Therapeutics                                                                                                                                                                                        Page 20 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
14.3.5 
Summary of Subject Assessed Local Skin Reactions (LSR); Safety Population 
 
Figures 
14.4.1.1.1.1 
CAL Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.1.1.1.2 
CAL Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.1.1.2.1 
BDP Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.1.1.2.2 
BDP Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.1.1.3.1 
MC1080Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.1.1.3.2 
MC1080Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.1.1.4.1 
Betamethasone 17-propionate Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.1.1.4.2 
Betamethasone 17-propionate Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.1.2.1.1 
CAL Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.1.2.1.2 
CAL Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.1.2.2.1 
BDP Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.1.2.2.2 
BDP Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.1.2.3.1 
MC1080Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.1.2.3.2 
MC1080Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.1.2.4.1 
Betamethasone 17-propionate Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.1.2.4.2 
Betamethasone 17-propionate Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.2.1.1.1 
Individual CAL Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.2.1.1.2 
Individual CAL Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.2.1.2.1 
Individual BDP Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.2.1.2.2 
Individual BDP Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.2.1.3.1 
Individual MC1080Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.2.1.3.2 
Individual MC1080Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.2.1.4.1 
Individual Betamethasone 17-propionate Concentration (Median) by Time Point, Linear Scale, Week 4 Serial PK Sampling 
14.4.2.1.4.2 
Individual Betamethasone 17-propionate Concentration (Median) by Time Point, Linear Scale, Week 8 Serial PK Sampling 
14.4.2.2.1.1 
Individual CAL Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.2.2.1.2 
Individual CAL Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.2.2.2.1 
Individual BDP Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.2.2.2.2 
Individual BDP Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.2.2.3.1 
Individual MC1080Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.2.2.3.2 
Individual MC1080Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
14.4.2.2.4.1 
Individual Betamethasone 17-propionate Concentration (Median) by Time Point, Semi-Log Scale, Week 4 Serial PK Sampling 
14.4.2.2.4.2 
Individual Betamethasone 17-propionate Concentration (Median) by Time Point, Semi-Log Scale, Week 8 Serial PK Sampling 
 
Listing Tables 
16.1.7 
Subject Enrolment and Randomization 
16.2.1.1 
Screen Failure 


MC2 Therapeutics                                                                                                                                                                                        Page 21 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
16.2.1.2 
Subject Disposition 
16.2.2 
Protocol Deviations 
16.2.3 
Population Datasets 
16.2.4.1 
Demographics and Baseline Characteristics 
16.2.4.2 
Prior and Concomitant Medication 
16.2.4.3 
Concurrent Procedures 
16.2.4.4 
Medical or Surgical History 
16.2.4.5 
Psoriasis Treatment History 
16.2.5.1 
Study Drug Administration and Compliance 
16.2.5.2 
Study Drug Accountability 
16.2.5.3.1 
Overall Study Drug Exposure and Compliance, Day 1 to Week 4 Period 
16.2.5.3.2 
Overall Study Drug Exposure and Compliance, Day 1 to Week 8 Period 
16.2.5.4.1 
Subject Treatment Diary Card 
16.2.5.4.2 
Subject Food Diary 
16.2.6.1 
Plasma Concentration Sample Date and Time and Plasma Concentrations 
16.2.6.2.1 
CAL Derived Pharmacokinetics Parameters  
16.2.6.2.2 
BDP Derived Pharmacokinetics Parameters  
16.2.6.2.3 
MC1080 Derived Pharmacokinetics Parameters  
16.2.6.2.4 
Betamethasone 17-propionate Derived Pharmacokinetics Parameters  
16.2.6.3 
Physician’s Global Assessment of Disease Severity (PGA) – Scalp, Trunk and/or Limbs 
16.2.6.4 
Investigator’s Assessment of the Body Surface Area (BSA) Involvement of Psoriasis 
16.2.6.5 
Investigator and Subject Assessed Local Skin Reaction (LSR) 
16.2.6.6 
Psoriasis Treatment Convenience Scale 
16.2.6.7 
ACTH Challenge (<18 μg/dL.) 
16.2.6.7 
ACTH Challenge (<14 μg/dL.) 
16.2.7.1 
Adverse Events 
16.2.7.2 
Serious Adverse Events 
16.2.7.3 
Adverse Events Leading to Study Drug Discontinuation 
16.2.8.1 
Urine Pregnancy Test 
16.2.8.2.1 
Clinical Laboratory Test Results; Biochemistry 
16.2.8.2.2 
Clinical Laboratory Test Results; Hematology 
16.2.8.2.3 
Clinical Laboratory Test Results; 24 Hour Urinalysis 
16.2.8.3 
Laboratory Values Outside of Normal Range 
16.2.8.4 
Vital Signs 
16.2.8.5 
Physical Examinations 
16.2.8.6 
12-Lead ECG Results 
16.2.9 
General Comments 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 22 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
 
 
MC2 Therapeutics  
                                                                         Page  1 of  1 
Protocol Number: MC2-01-C3 
Table 14.1.1: Summary of Subject Disposition 
 
 
MC2-01 Cream 
Active Comparator 
 
Overall 
 
 
 
 
 
Number of Subjects Screened  
 
 
 
XX 
Number of Subjects Randomized 
XX 
XX 
 
XX 
Number of Subjects in Safety Population, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Number of Subjects in HPA Population, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Number of Subjects in PK Population, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
Number of Subjects Completing the Study, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Number of Subjects Discontinued, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Reason for Discontinuation, n (%) 
 
 
 
 
 
Investigator discretion  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Unacceptable adverse events 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Exclusion criteria 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
HPA axis suppression at Visit 1/Day 0 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Albumin corrected serum calcium above upper limit at Visit 1/Day 0 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Trial suspended by Sponsor 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Voluntary withdrawal 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Other reasons  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Lost to follow-up  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
Death  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
Note: Denominator for percentages is the number of subjects randomized. 
 
Generated on  XX/XX/XX:XXXX  by SMYDS / Uses: XXXX / Reference: Data Listing XXXX  


MC2 Therapeutics                                                                                                                                                                                        Page 23 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.1.2.X: Summary of Subject Demographics and Baseline Characteristics 
[Safety Population] [HPA Population] [PK Population] 
 
 
MC2-01 Cream  
(N=XX) 
Active Comparator 
(N=XX) 
 
Overall 
(N=XX) 
Age (years) 
 
 
 
 
N 
XX 
XX 
 
XX 
Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
 
XX.X (XX.XX) 
Median 
XX.X 
XX.X 
 
XX.X 
Q1, Q3         
XX, XX 
XX, XX 
 
XX, XX 
Minimum, Maximum         
XX, XX 
XX, XX 
 
XX, XX 
 
 
 
 
 
Sex, n(%) 
 
 
 
 
Female 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Male 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
Race, n(%) 
 
 
 
 
White 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Black or African American 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Asian 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
American Indian or Alaska Native 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Native Hawaiian or Other Pacific Islander 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Other [1] 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
Ethnicity, n(%) 
 
 
 
 
Hispanic or Latino 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
Not Hispanic or Latino 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
[1] See listing 16.2.4.1 for other races. 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 24 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.1.2.X: Summary of Subject Demographics and Baseline Characteristics 
 [Safety Population] [HPA Population] [PK Population] 
 
 
MC2-01 Cream  
(N=XX) 
Active Comparator 
(N=XX) 
 
Overall 
(N=XX) 
Fitzpatrick Skin Type, n(%) 
 
 
 
 
I 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
II 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
III 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
<etc.> 
 
 
 
 
 
 
 
 
 
Height (cm) 
 
 
 
 
N 
XX 
XX 
 
XX 
Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
 
XX.X (XX.XX) 
Median 
XX.X 
XX.X 
 
XX.X 
Q1, Q3         
XX, XX 
XX, XX 
 
XX, XX 
Minimum, Maximum         
XX, XX 
XX, XX 
 
XX, XX 
 
 
 
 
 
Weight (kg) 
 
 
 
 
N 
XX 
XX 
 
XX 
Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
 
XX.X (XX.XX) 
Median 
XX.X 
XX.X 
 
XX.X 
Q1, Q3         
XX, XX 
XX, XX 
 
XX, XX 
Minimum, Maximum         
XX, XX 
XX, XX 
 
XX, XX 
 
 
 
 
 
 
 
 
 
 
Note: Height and weight can be self-reported. 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 25 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.1.2.X: Summary of Subject Demographics and Baseline Characteristics 
[Safety Population] [HPA Population] [PK Population] 
 
 
MC2-01 Cream  
(N=XX) 
Active Comparator 
(N=XX) 
Overall 
(N=XX) 
Baseline HPA Axis Suppression Status, n(%) 
 
 
 
Yes 
XX (XX.X) 
-- 
-- 
No 
XX (XX.X) 
-- 
-- 
Unknown 
XX (XX.X) 
-- 
-- 
 
 
 
 
Baseline PGA (Scalp, Trunk and/or Limbs), n(%) 
 
 
 
  0 – Clear 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  1 – Almost clear 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  2 – Mild 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  3 – Moderate 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  4 – Severe 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
Baseline Total BSA (%) 
XX 
XX 
XX 
N 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
Mean (SD) 
XX.X 
XX.X 
XX.X 
Median 
XX, XX 
XX, XX 
XX, XX 
Q1, Q3         
XX, XX 
XX, XX 
XX, XX 
Minimum, Maximum         
XX 
XX 
XX 
 
 
 
 
Duration of Psoriasis (years) [2] 
 
 
 
N 
XX 
XX 
XX 
Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
XX.X (XX.XX) 
Median 
XX.X 
XX.X 
XX.X 
Q1, Q3         
XX, XX 
XX, XX 
XX, XX 
Minimum, Maximum         
XX, XX 
XX, XX 
XX, XX 
 
 
 
 
 
 
 
 
 
[2] Calculated as year of baseline minus year of first psoriasis diagnosis 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 


MC2 Therapeutics                                                                                                                                                                                        Page 26 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  1 of  2 
Protocol Number: MC2-01-C3 
Table 14.1.3: Summary of Extent of Exposure and Compliance 
Safety Population 
 
Day 1 to Week 8 
 
Day 1 to Week 4 
MC2-01 Cream 
(N=XX) 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
Total Number of Days of Exposure[1] 
 
 
 
 
N 
XX 
 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
 
XX.X (XX.X) 
XX.X (XX.X) 
Median  
XX.X 
 
XX.X 
XX.X 
Q1, Q3  
XX, XX 
 
XX, XX 
XX, XX 
Minimum, Maximum  
XX, XX 
 
XX, XX 
XX, XX 
 
 
 
 
 
Total Number of Missed Doses 
 
 
 
 
N 
XX 
 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
 
XX.X (XX.X) 
XX.X (XX.X) 
Median  
XX.X 
 
XX.X 
XX.X 
Q1, Q3  
XX, XX 
 
XX, XX 
XX, XX 
Minimum, Maximum  
XX, XX 
 
XX, XX 
XX, XX 
 
 
 
 
 
Total Number of Doses Applied[2] 
 
 
 
 
N 
XX 
 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
 
XX.X (XX.X) 
XX.X (XX.X) 
Median  
XX.X 
 
XX.X 
XX.X 
Q1, Q3  
XX, XX 
 
XX, XX 
XX, XX 
Minimum, Maximum  
XX, XX 
 
XX, XX 
XX, XX 
 
 
 
 
 
[1] Total number of days of exposure is defined as the date of last application of study drug minus date of first application plus one. The last application is the in-clinic dosing at 
Week 4 visit (Day 1 to Week 4 period) and Week 8 visit (for Day 1 to Week 8 period).  
[2] Total number of doses applied= total number of doses required – total number of missed doses. Total number of doses required = total number of days of exposure – any days 
of investigator approved stop. 
 
Generated on  XX/XX/XX:XXXX  by SMYDM / Uses: XXXX / Reference: Data Listing XXXX  
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 27 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  1 of  2 
Protocol Number: MC2-01-C3 
Table 14.1.3: Summary of Extent of Exposure and Compliance 
Safety Population  
 
 
Day 1 to Week 8 
 
Day 1 to Week 4 
MC2-01 Cream 
(N=XX) 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
Total Amount of Drug Used (g)[3] 
 
 
 
 
N 
XX 
 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
 
XX.X (XX.X) 
XX.X (XX.X) 
Median  
XX.X 
 
XX.X 
XX.X 
Q1, Q3  
XX, XX 
 
XX, XX 
XX, XX 
Minimum, Maximum  
XX, XX 
 
XX, XX 
XX, XX 
 
 
 
 
 
Amount of Drug Used per Week (g/per week)[4] 
 
 
 
 
N 
XX 
 
XX 
XX 
Mean (SD) 
XX.X (XX.X) 
 
XX.X (XX.X) 
XX.X (XX.X) 
Median  
XX.X 
 
XX.X 
XX.X 
Q1, Q3  
XX, XX 
 
XX, XX 
XX, XX 
Minimum, Maximum  
XX, XX 
 
XX, XX 
XX, XX 
 
 
 
 
 
[3] Total amount of drug used (g) is defined as the summation of amount of drug used per kit for all returned kits. Amount of drug used per kit is the difference in weight between 
the returned and dispensed kits. Amount of drug used for sealed and unreturned kits will be assumed to be 0.0 g. 
[4] Amount of drug used per week (g/per week) is defined as the total amount of drug used divided by total number of days of exposure to the study drug multiplied by 7. 
 
Generated on  XX/XX/XX:XXXX  by SMYDM / Uses: XXXX / Reference: Data Listing XXXX   
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 28 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.1.4: Summary of Concomitant Medications 
by Anatomical Therapeutic Chemical Class (ATC) and Preferred Term 
Safety Population 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
 
 
 
 
 
   
Subjects with any Concomitant Medication, n (%) 
XX (XX.X) 
XX (XX.X) 
   
 
 
 
   
<< Anatomical Therapeutic Chemical Class >> 
 
 
   
          << Medication Preferred Term >> 
XXXXX 
XXXXX 
   
          << Medication Preferred Term >> 
XXXXX 
XXXXX 
   
          << Medication Preferred Term >> 
XXXXX 
XXXXX 
   
 
 
 
   
<< Anatomical Therapeutic Chemical Class >> 
 
 
   
          << Medication Preferred Term >> 
XXXXX 
XXXXX 
   
          << Medication Preferred Term >> 
XXXXX 
XXXXX 
   
          << Medication Preferred Term >> 
XXXXX 
XXXXX 
   
 
 
 
   
 
 
 
   
 
Note: Any medication ongoing or with stop date on or after Day 1 is a concomitant medication. Counts reflect number of subjects in each treatment group reporting one or more 
prior medication that map to the WHO Drug anatomical therapeutic chemical or preferred term. A subject may be counted once only in each row of the table. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 29 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.2.1.X: Summary of Plasma Concentration of [CAL, BDP,  MC1080, Betamethasone 17-propionate] (ng/mL) by Time Point 
PK Population 
[MC2-01 Cream] [Active Compartor] 
 
Time Point 
N 
Nquant 
Median 
Lower, Upper Quartiles 
Minimum, Maximum 
 
 
 
 
 
 
Baseline 
 
 
 
 
 
  Pre-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
Visit 2/Week 2 
 
 
 
 
 
  Pre-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
 
Visit 3/Week 4 
 
 
 
 
 
Pre-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
0.5 hours post-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
1 hour post-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
2 hours post-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
3 hours post-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
5 hours post-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
7 hours post-dose 
XX 
XX 
XX.X 
XX.X, XX.X 
XX.X, XX.X 
 
 
 
 
 
Visit 5/Week 8 
 
 
 
 
 
<include all time points> 
 
 
 
 
 
 
 
 
 
 
 
Note: Concentration below the limit of quantitation (< XX.X ng/mL) are reported as the lower limit of quantification (LLoQ) for calculating summary statistics. 
Nquant: number of samples in the N population with quantifiable levels of analyte;  
 
Generated on  XX/XX/XX:XXXX  by SMYXX  /  Uses: XXXX / Reference: Data Listing XXXX 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 30 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.2.2.X: Summary of [CAL, BDP,  MC1080, Betamethasone 17-propionate] (ng/mL) Pharmacokinetics Parameters 
PK Population 
 
N 
 
Median 
Lower Quartile,  
Upper Quartile 
Minimum,  
Maximum 
  
Week 4 
 
 
 
 
 
  
MC2-01 Cream (N=XX) 
 
 
 
 
 
  
Cmax (ng/mL) 
XX 
 
XXX.X 
XXX, XXX 
XXX, XXX 
  
Tmax (h) 
XX 
 
XXX.X 
XXX.X, XXX.X 
XXX.X, XXX.X 
  
AUC0-7 (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
AUC0-t (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
AUC0-∞ (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
T1/2 (h) 
XX 
 
XXX.X 
XXX.X, XXX.X 
XXX.X, XXX.X 
  
 
 
 
 
 
 
  
Active Comparator (N=XX) 
 
 
 
 
 
  
Cmax (ng/mL) 
XX 
 
XXX.X 
XXX, XXX 
XXX, XXX 
  
Tmax (h) 
XX 
 
XXX.X 
XXX.X, XXX.X 
XXX.X, XXX.X 
  
AUC0-7 (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
AUC0-t (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
AUC0-∞(ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
T1/2 (h) 
XX 
 
XXX.X 
XXX.X, XXX.X 
XXX.X, XXX.X 
  
 
 
 
 
 
 
  
Week 8 
 
 
 
 
 
  
MC2-01 Cream (N=XX) 
 
 
 
 
 
  
Cmax (ng/mL) 
XX 
 
XXX.X 
XXX, XXX 
XXX, XXX 
  
Tmax (h) 
XX 
 
XXX.X 
XXX.X, XXX.X 
XXX.X, XXX.X 
  
AUC0-7 (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
AUC0-t (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
AUC0-∞ (ng*h/mL) 
XX 
 
XXXX 
XXX, XXX 
XXX, XXX 
  
T1/2 (h) 
XX 
 
XXX.X 
XXX.X, XXX.X 
XXX.X, XXX.X 
  
 
 
 
 
 
 
  
 
 
Generated on  XX/XX/XX:XXXX  by SMYXX  /  Uses: XXXX / Reference: Data Listing XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 31 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.2.3.X: Assessment of Relative Systemic Exposure of [CAL, BDP,  MC1080, Betamethasone 17-propionate] (ng/mL) at Week 4 
PK Population 
 
 
 
Natural Log-Scale Difference[1] 
Geometric Mean Ratio (GMR) [2] 
 
N 
Estimate 
90% CI  
Estimate 
90% CI   
 
 
 
 
 
 
  Cmax (ng/mL) 
XX 
X.XXX 
X.XXX, X.XXX 
X.XXX 
X.XXX, X.XXX 
  AUC0-7 (ng*h/mL) 
XX 
X.XXX 
X.XXX, X.XXX 
X.XXX 
X.XXX, X.XXX 
 
 
 
 
 
 
[1] Difference and the associated 90% CI (confidence interval), are estimated by using an analysis of variance model for censored data including treatment group, using log-
transformed PK parameters. 
[2] Geometric Mean ratio (GMR) and the associated 90% CI are back transformed point estimate and the associated 90% CI. 
 
Generated on XXXXXX by XXXX /  Uses: XXXX  / Reference: Data Listing XXXX 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 32 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.2.4.1 Summary of HPA-Axis Suppression (Based on Cosyntropin US Packing Insert) 
HPA Population 
 
 
MC2-01 Cream 
(N=XX) 
 
 
 
 
  
HPA-Axis Suppression, n / N (%) 
 
 
  
Visit 3/ Week 4 
 
XX/XX (XX.X) 
  
 
 
 
  
Visit 5/ Week 8 
 
XX/XX (XX.X) 
  
     HPA-Axis Suppressed at Week 4 
 
XX/XX (XX.X) 
  
     HPA-Axis Not Suppressed at Week 4 
 
XX/XX (XX.X) 
  
 
 
 
  
 
 
 
  
 
 
 
  
Note: HPA-axis suppression is defined as a 30-minute post-stimulation cortisol level <18 μg/dL 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
[Programming note: Denominator for Visit 5/Week 8 (Week 4 HPA-Axis Suppressed) row is subjects with HPA-Axis Suppressed at Week 8;  denominator for Visit 5/Week 8 
(Week 4 HPA-Axis Not Suppressed) row is subjects with HPA-Axis Suppressed at Week 8] 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 33 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.2.4.2 Summary of HPA-Axis Suppression (Based on Lab Reference Range) 
MC2-01 Cream Subjects with Baseline Cortisol Level ≥ 14 µg/dl  
 
 
MC2-01 Cream 
(N=XX) 
 
 
 
 
  
HPA-Axis Suppression, n / N (%) 
 
 
  
Visit 3/ Week 4 
 
XX/XX (XX.X) 
  
 
 
 
  
Visit 5/ Week 8 
 
XX/XX (XX.X) 
  
     HPA-Axis Suppressed at Week 4 
 
XX/XX (XX.X) 
  
     HPA-Axis Not Suppressed at Week 4 
 
XX/XX (XX.X) 
  
 
 
 
  
 
 
 
  
 
 
 
  
Note: HPA-axis suppression is defined as a 30-minute post-stimulation cortisol level <14 μg/dL 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
[Programming note: Denominator for Visit 5/Week 8 (Week 4 HPA-Axis Suppressed) row is subjects with HPA-Axis Suppressed at Week 8;  denominator for Visit 5/Week 8 
(Week 4 HPA-Axis Not Suppressed) row is subjects with HPA-Axis Suppressed at Week 8] 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 34 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.2.5 Summary of Calcium Metabolism 
HPA Population 
 
 
MC2-01 Cream (N=XX) 
 
Observed Value 
Change from Baseline 
 
 
 
 
  
Albumin-Corrected Serum Calcium (unit) 
 
 
  
Baseline 
 
 
  
N 
XX 
-- 
  
Mean (SD) 
XX.X (XX.X) 
-- 
  
Median  
XX.X 
-- 
  
Q1, Q3  
XX, XX 
-- 
  
Minimum, Maximum  
XX, XX 
-- 
  
 
 
 
  
Visit 3/Week 4 
 
 
  
N 
XX 
XX 
  
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
  
Median  
XX.X 
XX.X 
  
Q1, Q3  
XX, XX 
XX, XX 
  
Minimum, Maximum  
XX, XX 
XX, XX 
  
 
 
 
  
Visit 5/Week 8 
 
 
  
N 
XX 
XX 
  
Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
  
Median  
XX.X 
XX.X 
  
Q1, Q3  
XX, XX 
XX, XX 
  
Minimum, Maximum  
XX, XX 
XX, XX 
  
 
 
 
  
<Continue for: 24 Hours Urinary Calcium Excretion (unit) and Ratio of Urinary Calcium to Creatinine> 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 35 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.2.6: Summary of Physician’s Global Assessment (PGA) 
Safety Population 
 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
 
 
 
 
 
Baseline 
  
 
   
 
     
Observed Value, n (%) 
 
 
   
 
     
N 
  
XX 
   
XX 
     
0 – Clear 
  
XX (XX.X) 
   
XX (XX.X) 
     
1 – Almost clear 
  
XX (XX.X) 
   
XX (XX.X) 
     
2 – Mild 
  
XX (XX.X) 
   
XX (XX.X) 
     
3 – Moderate 
  
XX (XX.X) 
   
XX (XX.X) 
     
4 – Severe 
  
XX (XX.X) 
   
XX (XX.X) 
     
 
  
 
   
 
     
Visit 3/Week 4 
  
 
   
 
     
Observed Value, n (%) 
 
 
   
 
     
N 
  
XX 
   
XX 
     
0 – Clear 
  
XX (XX.X) 
   
XX (XX.X) 
     
  <Etc.> 
  
XX (XX.X) 
   
XX (XX.X) 
     
Change From Baseline, n (%) 
 
   
 
     
N 
XX 
XX 
2 = Worsen by 2 
XX (XX.X) 
XX (XX.X) 
1 = Worsen by 1 
XX (XX.X) 
XX (XX.X) 
0 = No Change 
XX (XX.X) 
XX (XX.X) 
-1 = Improve by 1 
XX (XX.X) 
XX (XX.X) 
-2 = Improve by 2  
XX (XX.X) 
XX (XX.X) 
-3 = Improve by 3  
XX (XX.X) 
XX (XX.X) 
PGA Treatment Success [1]  
XX (XX.X) 
XX (XX.X) 
 
 [1] PGA success is defined as a minimum 2-point decrease from Baseline in the PGA. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 36 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.2.6: Summary of Physician’s Global Assessment (PGA) 
Safety Population 
 
 
MC2-01 Cream 
(N=XX) 
Active 
Comparator 
(N=XX) 
 
 
  
 
 
 
 
 
 
    
Visit 5/Week 8 
  
 
 
 
 
 
 
    
Observed Value, n (%) 
 
 
 
 
 
 
 
    
N 
  
XX 
 
 
 
-- 
 
    
0 – Clear 
  
XX (XX.X) 
 
 
 
-- 
 
    
<Etc.> 
  
XX (XX.X) 
 
 
 
-- 
 
    
Change From Baseline, n (%) 
 
 
 
 
 
 
    
N 
  
XX 
 
 
 
-- 
 
    
2 = Worsen by 2 
  
XX (XX.X) 
 
 
 
-- 
 
    
1 = Worsen by 1 
  
XX (XX.X) 
 
 
 
-- 
 
    
0 = No Change 
  
XX (XX.X) 
 
 
 
-- 
 
    
-1 = Improve by 1 
  
XX (XX.X) 
 
 
 
-- 
 
    
-2 = Improve by 2  
  
XX (XX.X) 
 
 
 
-- 
 
    
-3 = Improve by 3  
  
XX (XX.X) 
 
 
 
-- 
 
    
PGA Treatment Success [1]  
  
XX (XX.X) 
 
 
 
-- 
 
    
 
 [1] PGA success is defined as a minimum 2-point decrease from Baseline in the PGA. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 37 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.2.7: Summary of Psoriasis Treatment Convenience Score (PTCS) at Week 4 
 
 Safety Population 
 
 
 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
 
 
 
 
  
Total Score (Sum of Q1 to Q5)  
 
 
  
N 
XX 
XX 
  
Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  
Median 
XX.X 
XX.X 
  
Q1, Q3         
XX.X, XX.X 
XX.X, XX.X 
  
Minimum, Maximum         
XX.X, XX.X 
XX.X, XX.X 
  
 
 
 
  
Linear Mixed Effect Model[1] 
 
 
  
LSM (SE) 
XX.X(XX.X) 
XX.X(XX.X) 
  
LSM, 95% CI 
XX.X, XX.X 
XX.X, XX.X 
  
LSM Difference (MC2-01 Cream - Active Comparator) (SE) 
XX.X (XX.X) 
 
  
LSM Difference, 95% CI  
XX.X, XX.X 
 
  
 
 
 
  
Q1: How easy was the treatment to apply to the skin? 
 
 
  
N 
XX 
XX 
  
Mean (SD) 
XX.X (XX.XX) 
XX.X (XX.XX) 
  
Median 
XX.X 
XX.X 
  
Q1, Q3         
XX.X, XX.X 
XX.X, XX.X 
  
Minimum, Maximum         
XX.X, XX.X 
XX.X, XX.X 
  
 
 
 
  
 
 
 
  
<<Continue for 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?>> 
 
 
  
 
 
 
  
 
 
 
  
SE = Standard error; LSM = Least square means; CI = Confidence interval 
[1] The linear mixed effect model includes as a systematic effect and study site as a random effect.  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 38 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.1.1: Overall Summary of Adverse Events 
Safety Population 
 
 
Weeks 1 – 4 [1] 
 
Post Week 4 [2] 
 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
MC2-01 Cream 
(N=XX) 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
Number of Events 
XX 
XX 
 
XX 
 
Number of Subjects, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
Treatment-Emergent Adverse Events (TEAEs) 
 
 
 
 
 
Number of Events 
XX 
XX 
 
XX 
 
Number of Subjects, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
Treatment-Related TEAEs 
 
 
 
 
 
Number of Events 
XX 
XX 
 
XX 
 
Number of Subjects, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
Serious AEs (All) 
 
 
 
 
 
Number of Events 
XX 
XX 
 
XX 
 
Number of Subjects, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
Serious TEAEs  
 
 
 
 
 
Number of Events 
XX 
XX 
 
XX 
 
Number of Subjects, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
AEs Leading to Study Drug Discontinuation 
 
 
 
 
 
Number of Events 
XX 
XX 
 
XX 
 
Number of Subjects, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 Note: Counts reflect number of subjects reporting one or more adverse events that map to MedDRA 20.0. A subject will be counted once only within each AE category. TEAEs 
include all AEs starting or worsening after the first dose of study drug.  
 
Generated on  XX/XX/XX:XXXX  by SMYAE / Uses: XXXX / Reference: Data Listing XXXX 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 39 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.1.2: Summary of Treatment-emergent Adverse Events 
by System Organ Class and Preferred Term in Descending Frequency 
Safety Population 
 
 
Weeks 1 – 4 [1] 
 
Post Week 4 [2] 
 
System Organ Class 
          Preferred Term 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
MC2-01 Cream 
(N=XX) 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%) 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
<< Adverse Event Preferred Term >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
<< Adverse Event Preferred Term >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
<< Adverse Event Preferred Term >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
<< Adverse Event Preferred Term >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
<< Adverse Event Preferred Term >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
<< Adverse Event Preferred Term >> 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted once only in 
each row of the table.  
[1] Includes TEAEs with an onset date on or before Week 4 visit. 
[2] Includes TEAEs with an onset date after Week 4 visit. 
 
Generated on  XX/XX/XX:XXXX  by SMYTEAEPT / Uses: XXXX / Reference: Data Listings XXXX  
 
 
<Programming Note: sort by SOC in alphabetical order and PT in descending order of the combined frequency in the two active treatments> 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 40 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.1.3: Summary of Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and Maximum Severity 
Safety Population 
 
 
 
Weeks 1 – 4 [1] 
 
Post Week 4 [2] 
 
System Organ Class 
          Preferred Term 
Severity 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
MC2-01 Cream 
(N=XX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%) 
Severe 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Moderate 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Mild 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Severe 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Moderate 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Mild 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Severe 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Moderate 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Mild 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at 
the highest severity. AEs are categorized by onset date. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 


MC2 Therapeutics                                                                                                                                                                                        Page 41 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.1.4: Summary of Treatment-emergent Adverse Events 
by System Organ Class, Preferred Term, and Maximum Causality 
Safety Population 
 
 
 
Weeks 1 – 4 [1] 
 
Post Week 4 [2] 
 
System Organ Class 
          Preferred Term 
Causality  
Assessment[1] 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
MC2-01 Cream 
(N=XX) 
 
 
 
 
 
 
 
 
Subjects with any TEAE, n (%) 
Related  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Not Related 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
<< Adverse Event System Organ Class >> 
Related  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Not Related 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
          << Adverse Event Preferred Term >> 
Related  
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
Not Related 
XX (XX.X) 
XX (XX.X) 
 
XX (XX.X) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Counts reflect numbers of subjects reporting one or more adverse events that map to MedDRA system organ class or preferred term. A subject may be counted only once at 
the highest severity. AEs are categorized by onset date. 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX  
 


MC2 Therapeutics                                                                                                                                                                                        Page 42 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.2.1.X: Summary of Clinical Laboratory Results by Treatment and Visit 
[Biochemistry][Hematology] 
Safety Population 
[Lab Tests Name (Units)] 
 
 
MC2-01 Cream (N=XX) 
Active Comparator (N=XX) 
  
 
Observed Value 
CFBL 
Relative CFBL 
Observed Value 
CFBL 
Relative CFBL 
    
 
 
 
 
 
 
 
    
Baseline 
 
 
 
 
 
 
    
  N 
XX 
 
 
XX 
 
 
    
  Mean (SD) 
XX.X (XX.X) 
 
 
XX.X (XX.X) 
 
 
    
  Median 
XX.X 
 
 
XX.X 
 
 
    
  CV (%) 
XX.X 
 
 
XX.X 
 
 
    
  Q1, Q3         
XX.X, XX.X 
 
 
XX.X, XX.X 
 
 
    
  Minimum, Maximum         
XX.X, XX.X 
 
 
XX.X, XX.X 
 
 
    
 
 
 
 
 
 
 
    
Visit 3/Week 4 
 
 
 
 
 
 
    
  N 
XX 
XX 
XX 
XX 
XX 
XX 
    
  Mean (SD) 
XX.X (XX.X) 
XX.X (XX.X) 
XX.X (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 
    
  CV (%) 
XX.X 
- 
- 
XX.X 
- 
- 
    
  Q1, Q3         
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
    
  Minimum, Maximum         
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
XX.X, XX.X 
    
 
 
 
 
 
 
 
    
Visit 5/Week 8 
 
 
 
 
 
 
    
  N 
XX 
XX 
XX 
-- 
-- 
-- 
    
  <Etc.> 
 
 
 
 
 
 
    
 
 
 
 
 
 
 
    
 
CFBL=Change from baseline; CV = Coefficient of Variation. 
Note: Relative CFBL is defined as ratio of the post-baseline vs baseline value 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
<Programming Note: Serum biochemistry tests include: cortisol, urea, glucose, creatinine, calcium, albumin, calcium (albumin corrected), sodium, potassium, chloride, calcium, 
phosphate, alkaline phosphatase (ALP), plasma parathyroid hormone (PTH). Hematology tests include: hemoglobin, hematocrit, red blood cell (RBC) count, mean corpuscular 
volume (MCV), white blood cell (WBC) count. Page break after each lab parameter.> 


MC2 Therapeutics                                                                                                                                                                                        Page 43 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.2.2.X: Clinical Laboratory Results, Shifts from Baseline 
[Biochemistry][Hematology] 
Safety Population 
[Lab Tests Name (Units)] 
 
 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
 
 
 
 
 
 
 
 
Baseline - > Visit 3/Week 4, n (%) 
 
 
 
 
 
  Low ->  Normal 
 
XX (XX.X) 
XX (XX.X) 
 
 
  Normal -> Normal 
 
XX (XX.X) 
XX (XX.X) 
 
 
  High ->  Normal 
 
XX (XX.X) 
XX (XX.X) 
 
 
  Normal -> Missing 
 
XX (XX.X) 
XX (XX.X) 
 
 
  Missing ->  Low 
 
XX (XX.X) 
XX (XX.X) 
 
 
<Include all possible shifts as rows> 
 
 
 
 
 
 
 
 
 
 
 
Baseline - > Most Extreme Post-Baseline Value up to Visit 3/Week 4, n (%) 
 
 
 
 
 
  Low ->  Normal 
 
XX (XX.X) 
XX (XX.X) 
 
 
  Normal -> Normal 
 
XX (XX.X) 
XX (XX.X) 
 
 
  High ->  Normal 
 
XX (XX.X) 
XX (XX.X) 
 
 
  Normal -> Missing 
 
XX (XX.X) 
XX (XX.X) 
 
 
  Missing ->  Low 
 
XX (XX.X) 
XX (XX.X) 
 
 
<Include all possible shifts as rows> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Denominator is number of subjects with available baseline and post-baseline visit.  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 44 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.3: Summary of Vital Signs by Treatment and Visit 
Safety Population 
[Pulse Rate (bpm)][Systolic Blood Pressure (mmHg)][Diastolic Blood Pressure (mmHg)] 
 
 
MC2-01 Cream (N=XX) 
Active Comparator (N=XX) 
 
 
Observed Value 
Change from Baseline 
Observed Value 
Change from Baseline 
  
 
 
 
 
 
  
Baseline 
 
 
 
 
  
N 
XX 
 
XX 
 
  
Mean (SD) 
XX (XX.X) 
 
XX (XX.X) 
 
  
Median 
XX (XX.X) 
 
XX (XX.X) 
 
  
Q1, Q3 
XX, XX 
 
XX, XX 
 
  
Minimum, Maximum 
XX, XX 
 
XX, XX 
 
  
 
 
 
 
 
  
Visit 2/Week 2 
 
 
 
 
  
N 
XX 
XX 
XX 
XX 
  
Mean (SD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  
Median 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  
Q1, Q3 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  
Minimum, Maximum 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  
 
 
 
 
 
  
Visit 3/Week 4 
 
 
 
 
  
N 
XX 
XX 
XX 
XX 
  
Mean (SD) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  
Median 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
XX (XX.X) 
  
Q1, Q3 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  
Minimum, Maximum 
XX, XX 
XX, XX 
XX, XX 
XX, XX 
  
 
 
 
 
 
  
<<Continue for all visits>> 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 45 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
 
Table 14.3.4: Summary of Investigator Assessed Local Skin Reactions (LSR) 
Safety Population 
 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
 
 
 
 
 
Baseline 
 
 
 
Perilesional Signs 
 
 
 
Erythema, n(%) 
 
 
 
N 
XX 
XX 
 
0 – Absent 
XX (XX.X) 
XX (XX.X) 
 
1 – Mild 
XX (XX.X) 
XX (XX.X) 
 
2 – Moderate 
XX (XX.X) 
XX (XX.X) 
 
3 – Severe 
XX (XX.X) 
XX (XX.X) 
 
<<Continue for Scaling, Edema, Atrophy, Vesicles, Erosion/Ulceration>> 
 
 
 
 
Lesional Signs 
 
 
 
Vesicles, n(%) 
 
 
 
N 
XX 
XX 
 
0 – None 
XX (XX.X) 
XX (XX.X) 
 
1 – Mild 
XX (XX.X) 
XX (XX.X) 
 
2 – Moderate 
XX (XX.X) 
XX (XX.X) 
 
3 – Severe 
XX (XX.X) 
XX (XX.X) 
 
<<Continue Erosion/Ulceration>> 
 
 
 
 
<<Continue for all visits>> 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 46 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
Table 14.3.5: Summary of Subject Assessed Local Skin Reactions (LSR)  
Safety Population 
 
 
MC2-01 Cream 
(N=XX) 
Active Comparator 
(N=XX) 
 
 
 
 
 
Baseline 
 
 
 
Burning or Pain, n(%) 
 
 
 
 N 
XX 
XX 
 
  0 – Absent 
XX (XX.X) 
XX (XX.X) 
 
  1 – Mild 
XX (XX.X) 
XX (XX.X) 
 
  2 – Moderate 
XX (XX.X) 
XX (XX.X) 
 
  3 – Severe 
XX (XX.X) 
XX (XX.X) 
 
 
 
 
 
<<Continue for all visits>> 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX / Reference: Data Listings XXXX 
 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 47 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
  
Figure 14.4.1.1.X.Y: [CAL, BDP,  MC1080, Betamethasone 17-propionate] Concentration (Median) by Time Point, Linear Scale 
[Week 4 Serial PK Sampling] [Week 8 Serial PK Sampling] 
PK Population 
 
 
 
 
 
 
 
 
Plasma Concentration 
(unit) 
 
 
 
 
 
 
 
 
 
 
 
[Time (hours)] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Nominal sample collection times used in this figure. Concentrations below the limit of quantitation are reported as lower limit of quantification (LLOQ=XXXX).   
 
Generated on XX/XX/XX XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference:  
[Programming Note: include all time points pre-dose (0), 0.5, 1, 2, 3, 5, 7 Hour. The plot will include 2 lines (MC2-01 Cream and Active Comparator) at Week 4, 1 line (MC2-01 
Cream) at Week 8.] 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 48 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
  
Figure 14.4.1.2.X.Y: [CAL, BDP,  MC1080, Betamethasone 17-propionate] Concentration (Median) by Time Point, Semi-Log Scale 
[Week 4 Serial PK Sampling] [Week 8 Serial PK Sampling] 
PK Population 
 
 
 
 
 
 
 
 
Plasma Concentration 
(unit) 
 
 
 
 
 
 
 
 
 
 
 
[Time (hours)] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Nominal sample collection times used in this figure. Concentrations below the limit of quantitation are reported as  lower limit of quantification (LLOQ=XXXX).   
 
Generated on XX/XX/XX XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference:  
[Programming Note: include all time points pre-dose (0), 0.5, 1, 2, 3, 5, 7 Hour. The plot will include 2 lines (MC2-01 Cream and Active Comparator) at Week 4, 1 line (MC2-01 
Cream) at Week 8.] 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 49 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
  
Figure 14.4.2.1.X.Y: Individual [CAL, BDP,  MC1080, Betamethasone 17-propionate] Concentration (Median) by Time Point, Linear Scale 
[Week 4 Serial PK Sampling] [Week 8 Serial PK Sampling] 
PK Population 
[MC2-01 Cream] [Active Comparator] 
Subject: XXXX 
 
 
 
 
 
 
 
 
Plasma Concentration 
(unit) 
 
 
 
 
 
 
 
 
 
 
 
[Time (hours)] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Actual sample collection times used in this figure.   
 
Generated on XX/XX/XX XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference:  
[Programming Note: include all time points pre-dose (0), 0.5, 1, 2, 3, 5, 7 Hour.] 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 50 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics  
                                                                         Page  X of  Y 
Protocol Number: MC2-01-C3 
  
Figure 14.4.2.2.X.Y: Individual [CAL, BDP,  MC1080, Betamethasone 17-propionate] Concentration (Median) by Time Point, Semi-Log Scale 
[Week 4 Serial PK Sampling] [Week 8 Serial PK Sampling] 
PK Population 
[MC2-01 Cream] [Active Comparator] 
Subject: XXXX 
 
 
 
 
 
 
 
 
Plasma Concentration 
(unit) 
 
 
 
 
 
 
 
 
 
 
 
[Time (hours)] 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: Actual sample collection times used in this figure.   
 
Generated on XX/XX/XX XX:XX by XXXX / Uses: XXXX, XXXX, XXXX / Reference:  
[Programming Note: include all time points pre-dose (0), 0.5, 1, 2, 3, 5, 7 Hour.] 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 51 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.1.7:  Subject Enrollment and Randomization 
All Randomized Subjects 
 
Subject 
Number 
Date of Informed 
Consent 
Require Washout 
Period?/ Exclusion 
Criteria 
Washout Start 
Date 
Satisfy All 
I/E Criteria? 
Randomization 
Date 
Randomization 
Number 
Randomized 
Treatment 
Actual Treatment  
 
 
 
 
 
 
 
 
 
 
XX-XXX 
DDMMMYYYY 
Yes / Exclusion X 
DDMMYYYY  
No: Inclusion XX 
DDMMMYYYY 
XXXX 
MC2-01 Cream 
MC2-01 Cream 
 
XX-XXX 
DDMMMYYYY 
No 
-- 
Yes 
DDMMMYYYY 
XXXX 
Active Comparator Active Comparator  
XX-XXX 
DDMMMYYYY 
No 
-- 
Yes 
DDMMMYYYY 
XXXX 
MC2-01 Cream 
Not Treated 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX   by XXXX / Uses: XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 52 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.1.1: Screen Failures 
All Screen Failure Subjects 
 
Subject 
Number 
Date of Informed  
Consent 
Date of  
Screening 
Birth Month/Year 
Age  
(Years) 
Sex 
Primary Reason for  
Screen Failure 
 
 
 
 
 
 
XX-XXX 
DDMMMYYYY 
DDMMMYYYY 
MMMYYYY 
XX 
X 
I/E criteria not met: Inclusion 2 
XX-XXX 
DDMMMYYYY 
DDMMMYYYY 
MMMYYYY 
XX 
X 
Other: XXXXXXX 
XX-XXX 
DDMMMYYYY 
DDMMMYYYY 
MMMYYYY 
XX 
X 
XXXXXXXXXXX 
XX-XXX 
DDMMMYYYY 
DDMMMYYYY 
MMMYYYY 
XX 
X 
XXXXXXXXXXX 
XX-XXX 
DDMMMYYYY 
DDMMMYYYY 
MMMYYYY 
XX 
X 
XXXXXXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX  / Uses: XXXX 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 53 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.1.2: Subject Disposition 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
 
Date (Day) of [1] 
Subject 
Number 
Screening 
Randomization 
First Dose 
Last Dose 
Last Visit 
Last Contact 
Completion 
Status / 
Discontinuation 
Reason 
 
 
 
 
 
 
 
 
 
 
XX-XXX 
DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) XXXXX 
 
XX-XXX 
DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) DDMMMYYYY(XX) XXXXX 
 
001-001 
19JUN2017(-10) 
29JUN2017(1) 
29JUN2017(1) 
-- 
06JUL2017(8) 
-- 
Completed 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 54 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.2: Protocol Deviation 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
 
 
<Programming Note: The format of protocol deviation listing depends on the actual protocol deviation report form layout.  Additional columns may be added, such as 
“Reference” “Type”. If site deviation or deviation for SF subjects are also available, include those at the very end of this listing.> 
 
 
 
Subject 
Number 
Category 
Major/Minor 
Protocol Deviation 
 
 
 
 
XX-XXX 
XXXX 
Minor 
XXXXXXXXXXXX 
 
XXXXX 
Major 
XXXX 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 55 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.3: Population Datasets 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
 
 
 
Subject Number In Safety Population? In HPA Population? 
In PK Population? 
Reason for Exclusion from 
Safety Population 
Reason for Exclusion from 
HPA Population 
Reason for Exclusion from 
PK Population 
 
 
 
 
 
 
 
XX-XXX 
Yes 
Yes 
No 
NA 
NA 
XXX 
XX-XXX 
No 
No 
No 
XXX 
XXX 
XXX 
XX-XXX 
XXX 
XXX 
XXX 
NA 
NA 
NA 
 
 
  
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 56 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.4.1: Demographics and Baseline Characteristics  
All Randomized Subjects  
[MC2-01 Cream][Active Comparator] 
 
 
 
 
Subject 
Number 
Age (years) 
Sex 
Race 
Ethnicity 
Weight (kg) 
Height (cm) 
Fitzpatrick 
Skin Type 
HPA-axis 
Suppression 
Status[1] 
PGA 
Total BSA 
(%) 
Duration of 
Psoriasis 
(years) 
 
 
 
 
 
 
 
 
 
 
 
 
XX-XXX 
XX 
M 
Asian 
NH 
XXX 
XXX 
X 
Yes 
X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
XX-XXX 
XX 
F 
White 
H 
XXX 
XXX 
X 
No 
X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Note: PGA = Physician’s Global Assessment; BSA = Body Surface Area. NH=Not Hispanic or Latino; H=Hispanic or Latino 
[1] HPA-axis suppression status is only assessed among subjects assigned to MC2-01 cream. 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 
 


MC2 Therapeutics                                                                                                                                                                                        Page 57 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.4.2: Prior and Concomitant Medication 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Category 
WHO Preferred Term 
(Verbatim Term) /  
ATC Classification 
Topical treatment within 2 cm of treatment 
area?/ Indication 
Dose(Frequency)/Unit /Route 
Administered for 
AE #/ MH # 
Start Date (Day)-Stop Date (Day)  
 
 
 
 
 
 
XX-XXX 
Prior 
XXXXXX (xxxxx)/ 
XXXXXX 
Yes/XXX 
XX/XXX/XXXX 
NA/1 
DDMMMYYYY (XX) – 
DDMMMYYYY (XX) 
 
 
 
 
 
 
XX-XXX 
Concomitant 
XXXXXX (xxxxx)/ 
XXXXXX 
No/XXX 
XX/XXX/XXXX 
NA/NA 
DDMMMYYYY (XX) –  
Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 
 
<Programming Note: List medication in ascending start date for each subject.> 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 58 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.4.3: Concurrent Procedures 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject Number 
Preferred Term/ 
System Organ Class/ 
Procedure 
Inside treatment area?/  
Diagnosis/Body Location 
Administered for 
AE #/ MH # 
Procedure Start Date (Day)-Stop Date (Day)  
 
 
 
 
 
XX-XXX 
XXXXXXXX/ 
XXXXX/ 
XXXXXX 
Yes/  
XXXX/XXXXXXX 
1/NA 
DDMMMYYYY (XX) – DDMMMYYYY (XX) 
 
 
 
 
 
XX-XXX 
XXXXXXXX/ 
XXXXX/ 
XXXXXX 
No/  
XXXX/XXXXXXX 
NA/NA 
DDMMMYYYY (XX) – DDMMMYYYY (XX) 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX/ Uses: XXXX 
 
<Programming Note: List medication in ascending start date for each subject.> 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 59 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.4.4: Medical or Surgical History 
All Randomized Subjects 
 [MC2-01 Cream][Active Comparator] 
 
 
 
 
Subject Number 
MH # 
Diagnosis / Procedure 
System Organ Class 
Preferred Term 
Ongoing?  
 
 
 
 
 
 
XX-XXX 
1 
XXXX 
XXXXX 
 
XXXXXX 
No 
 
 
 
 
 
 
XX-XXX 
1 
XXXX 
XXXXX 
XXXXXX 
Yes  
 
 
 
 
 
 
 
 
 
 
 
 
  
Generated on  XX/XX/XX:XXXX  by  XXXX / Uses: XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 60 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                             Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.4.5: Psoriasis Treatment History 
All Randomized Subjects  
[MC2-01 Cream][Active Comparator] 
 
 
 
 
Subject 
Number 
Year of First Diagnosis of Psoriasis 
 
Previous Treatment 
 
 
 
 
XX-XXX 
YYYY 
 
TNF-a inhibitors 
 
 
 
 
XX-XXX 
YYYY 
 
Topical: retinoids 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by  XXXX / Uses: XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 61 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.5.1: Study Drug Administration and Compliance 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
 
Visit 
Visit Date (Day)[1] 
Apply Study Drug  
Once Daily Since Last Visit? 
Number of  
Missed Applications 
Approved Stop Date (Day) [1] 
Reason Missed 
 
 
 
 
 
 
 
 
XX-XXX  Visit 2/Week 2 DDMMMYYYY(XX) 
Y 
XX 
NA 
NA 
 
 Visit 3/Week 4 DDMMMYYYY(XX) 
Y 
XX 
NA 
NA 
 
 Visit 4/Week 6 DDMMMYYYY(XX) 
Y 
XX 
NA 
NA 
 
 Visit 5/Week 8 DDMMMYYYY(XX) 
N 
XX 
DDMMMYYYY(XX) 
XXXXXXXXXXX 
 
 
 
 
 
 
 
 
XX-XXX  Visit 2/Week 2 DDMMMYYYY(XX) 
Y 
XX 
NA 
NA 
 
 Visit 3/Week 4 DDMMMYYYY(XX) 
Y 
XX 
NA 
NA 
 
 Visit 4/Week 6 DDMMMYYYY(XX) 
N 
XX 
NA 
NA 
 
 Visit 5/Week 8 DDMMMYYYY(XX) 
N 
XX 
DDMMMYYYY(XX) 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 62 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.5.2: Study Drug Accountability 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Kit Number 
Date (Day)  
Dispensed [1] 
Tube Number Tube Retuned? Date (Day) Returned [1] 
Tube Sealed? Return Weight (g) 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
XXXXXXX 
DDMMMYYYY(XX) 
1 
Yes 
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
2 
No 
DDMMMYYYY(XX) 
- 
- 
 
Visit 2/Week 2 
XXXXXXX 
DDMMMYYYY(XX) 
1 
Yes 
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
2 
Redispensed 
- 
- 
- 
 
Visit 3/Week 4 
XXXXXXX 
DDMMMYYYY(XX) 
1 
XXXX 
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
2 
XXXX 
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
XXXXXXX 
DDMMMYYYY(XX) 
1 
Redispensed  
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
2 
No 
DDMMMYYYY(XX) 
XX 
XX.X 
 
Visit 2/Week 2 
XXXXXXX 
DDMMMYYYY(XX) 
1 
Yes 
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
2 
Redispensed 
DDMMMYYYY(XX) 
XX 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 63 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.5.3.1: Overall Study Drug Exposure and Compliance, Day 1 to Week 4 Period 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Total Number of Days 
of Exposure[1] 
Total Number of 
Expected Doses[2] 
Total Number of 
Missed Doses 
Total Number of 
Applied Doses[3] 
Total Amount of Drug 
Used (g)[4] 
Amount of Drug Used per 
week (g/per week)[5] 
   
 
 
 
 
 
 
 
   
XX-XXX 
XX 
XX 
XX 
XX 
XX.X 
XX.X 
   
 
 
 
 
 
 
 
   
XX-XXX 
XX 
XX 
XX 
XX 
XX.X 
XX.X 
   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
[1] Total number of days of exposure to the study drug is defined as the date of last application of study drug minus date of first application plus one. Last application is applied 
in-clinic at Week 4 visit.  
[2] Total number of expected doses is defined as total number of days of exposure minus any days of investigator approved stop (if applicable) 
[3] Total number of doses applied, defined as the total number of doses required minus total number of doses missed.  
[4] Total amount of drug used (g), defined as the summation of amount of drug used per kit for all dispensed kits.  
[5] Amount of drug used per week (g/per week), defined as the total amount of drug used divided by total number of days of exposure to the study drug multiplied by 7.  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 64 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.5.3.2: Overall Study Drug Exposure and Compliance, Day 1 to Week 8 Period 
All Randomized Subjects 
[MC2-01 Cream] 
 
Subject 
Number 
Total Number of Days 
of Exposure[1] 
Total Number of 
Expected Doses[2] 
Total Number of 
Missed Doses 
Total Number of 
Applied Doses[3] 
Total Amount of Drug 
Used (g)[4] 
Amount of Drug Used per 
week (g/per week)[5] 
   
 
 
 
 
 
 
 
   
XX-XXX 
XX 
XX 
XX 
XX 
XX.X 
XX.X 
   
 
 
 
 
 
 
 
   
XX-XXX 
XX 
XX 
XX 
XX 
XX.X 
XX.X 
   
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
   
 
[1] Total number of days of exposure to the study drug is defined as the date of last application of study drug minus date of first application plus one. Last application is applied 
in-clinic at Week 8 visit.  
[2] Total number of expected doses is defined as total number of days of exposure minus any days of investigator approved stop (if applicable) 
[3] Total number of doses applied, defined as the total number of doses required minus total number of doses missed.  
[4] Total amount of drug used (g), defined as the summation of amount of drug used per kit for all dispensed kits.  
[5] Amount of drug used per week (g/per week), defined as the total amount of drug used divided by total number of days of exposure to the study drug multiplied by 7.  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 65 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.5.4.1: Subject Treatment Diary Card 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Date (Day)[1] 
Study Drug Applied? 
Reason if Medication not Applied 
 
 
 
 
 
 
 
XX-XXX 
DDMMMYYYY (1) 
Y 
- 
 
 
DDMMMYYYY (XX) 
Y 
- 
 
 
DDMMMYYYY (XX) 
N 
XXXXXXX 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 66 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.5.4.2: Subject Food Diary 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Time Point 
Date (Day)[1] 
Number of Servings of 
Calcium-rich Foods 
Reason Not Done 
 
 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
Day -3 
DDMMMYYYY (-3) 
X 
NA 
 
 
 
Day -2 
DDMMMYYYY (-2) 
X 
NA 
 
 
 
Day -1 
DDMMMYYYY (-1) 
X 
XXXXXXX 
 
 
 
Collection Day 
DDMMMYYYY (1) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 67 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Listing 16.2.6.1: Plasma Concentration Sample Date and Time and Plasma Concentrations 
PK Population 
[MC2-01 Cream] [Active Comparator] 
 
Subject 
Visit 
Dosing Date and Time 
PK Time Point 
Sample Collection Date and 
Time (Day) 
Elapsed 
Time 
(hours) 
CAL 
(unit) 
BDP 
(unit) 
MC1080 
(unit) 
Betamethasone 
17-propionate 
(unit) 
 
 
 
 
 
 
 
 
 
 
XX-
XXX 
Baseline 
-- 
-- 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Visit 2/ 
Week 2 
DDMMYYYYTXX:XX 
Pre-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Visit 3/ 
Week 4 
DDMMYYYYTXX:XX 
Pre-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
0.5 hour post-
dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
1 hour post-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
2 hours post-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
3 hours post-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
5 hours post-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
7 hours post-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
<etc.> 
 
 
 
 
 
 
 
Visit 5/ 
Week 8 
DDMMYYYYTXX:XX 
Pre-dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
0.5 hour post-
dose 
DDMMYYYYTXX:XX (XX) 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
<etc.> 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 68 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                            Page X of Y 
Protocol Number: MC2-01-C3 
 
Listing 16.2.6.2.X: [CAL, BDP, MC1080, Betamethasone 17-propionate] Derived Pharmacokinetics Parameters  
PK Population 
[MC2-01 Cream] [Active Comparator] 
 
 
 
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 
 
[Programming Note: Week 8 only applies to MC2-01 Cream subjects] 
 
Subject 
Visit 
Cmax (ng/mL) 
Tmax (h) 
AUC0-7 (ng*h/mL ) 
AUC0-t (ng*h/mL) 
AUC0-∞ (ng*h/mL) 
T1/2 (h) 
    
 
 
 
 
 
 
 
 
    
XXX-XXX 
Week 4 
XXXX 
XXXX 
XX.XX 
XXXXX 
XXXXX 
XXXX 
    
 
 
 
 
 
 
 
 
    
 
Week 8 
XXXX 
XXXX 
XX.XX 
XXXXX 
XXXXX 
XXXX 
    
 
 
 
 
 
 
 
 
    


MC2 Therapeutics                                                                                                                                                                                        Page 69 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.6.3: Physician’s Global Assessment of Disease Severity (PGA) – Scalp, Trunk and/or Limbs  
All Randomized Subjects 
 [MC2-01 Cream][Active Comparator] 
  
  
  
  
  
  
  
Subject Number 
Visit 
Visit Date (Day) [1] 
 
 
 
Treatment 
Success?[2]  
PGA 
Change from Baseline 
 
 
 
 
 
 
 
XX-XXX 
Screening 
DDMMMYYYY(XX) 
 
3 – Moderate 
-- 
-- 
 
Visit 1/Day 1 
DDMMMYYYY(XX) 
 
3 – Moderate 
-- 
-- 
 
Visit 2/Week 2 
DDMMMYYYY(XX) 
 
2 – Mild 
-1 
N 
 
Visit 3/Week 4 
DDMMMYYYY(XX) 
 
2 – Mild 
-1 
N 
 
Visit 4/Week 6 
DDMMMYYYY(XX) 
 
1 – Almost clear 
-2 
Y 
 
Visit 5/Week 8 
DDMMMYYYY(XX) 
 
1 – Almost clear 
-2 
Y 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
[2] PGA success is defined as a minimum 2-point decrease from Baseline in the PGA. 
 
   
 
 
 
 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 70 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.6.4: Investigator’s Assessment of the Body Surface Area (BSA) Involvement of Psoriasis 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Visit Date (Day) [1] 
Scalp BSA (%) 
Neck, Trunk and/or Limbs BSA (%) 
Total BSA (%) 
 
 
 
 
 
 
 
 
XX-XXX 
Screening 
DDMMMYYYY(XX) 
XX.X 
XX.X 
XX.X 
 
 
Visit 1/Day 1 
DDMMMYYYY(XX) 
XX.X 
XX.X 
XX.X 
 
 
Visit 3/Week 4 
DDMMMYYYY(XX) 
XX.X 
XX.X 
XX.X 
 
 
Visit 5/Week 8 
DDMMMYYYY(XX) 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 [1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
  
 


MC2 Therapeutics                                                                                                                                                                                        Page 71 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.6.5: Investigator and Subject Assessed Local Skin Reaction (LSR) 
All Randomized Subjects 
 [MC2-01 Cream][Active Comparator] 
  
  
  
  
  
  
  
 
 
 
Investigator Assessed 
 
Subject 
Assessed 
Subject 
Number 
Visit 
Visit Date (Day) [1] 
Perilesional Signs 
Lesional Signs 
Burning or 
Pain 
Erythema 
Scaling 
Edema 
Atrophy 
Vesicles 
Erosion/ 
Ulceration 
Vesicles 
Erosion/ 
Ulceration 
 
 
 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
DDMMMYYYY(XX) 
1=Mild 
1=Mild 
1=Mild 
3=Severe 
X 
X 
X 
X 
 
X 
 
Visit 2/Week 2 
DDMMMYYYY(XX) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Visit 3/Week 4 
DDMMMYYYY(XX) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Visit 4/Week 6 
DDMMMYYYY(XX) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
Visit 5/Week 8 
DDMMMYYYY(XX) 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 72 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.6.6: Psoriasis Treatment Convenience Scale 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject Number 
Visit 
Visit Date (Day) [1] 
Q1 
Q2 
Q3 
Q4 
Q5 
Q6 
 Total Score of Q1-Q5 
 
 
 
 
 
 
 
 
 
 
  
 
XX-XXX 
Visit 3/Week 4 
DDMMMYYYY(XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 XX 
 
 
 
 
 
 
 
 
 
 
  
 
XX-XXX 
Unscheduled 
DDMMMYYYY(XX) 
XX 
XX 
XX 
XX 
XX 
XX 
 XX 
 
 
 
 
 
 
 
 
 
 
 
 
 
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? 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 73 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.6.7: ACTH Challenge 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Date (Day) [1] 
Cosyntropin 
Injection Time 
Pre-Stimulation 
30 Min Post-Stimulation 
HPA-Axis 
Suppression 
Collection Time 
Cortisol Level 
(μg/dL) 
Collection Time 
Cortisol Level 
(μg/dL) 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
DDMMMYYYY (XX) 
HH:MM 
HH:MM 
XX.X 
HH:MM 
XX.X 
No 
 
Visit 3/Week 4 
DDMMMYYYY (XX) 
HH:MM 
HH:MM 
XX.X 
HH:MM 
XX.X 
No 
 
Visit 4/Week 8 
DDMMMYYYY (XX) 
HH:MM 
HH:MM 
XX.X 
HH:MM 
XX.X 
Yes 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
 
 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 74 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.7.1: Adverse Events 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
AE 
# 
MedDRA SOC Term/ 
MedDRA Preferred 
Term / 
(Verbatim Term)  
TEAE? [1] / Period 
Onset Date (Day) –  
End Date (Day) [2] 
Related to 
Cosyntropin?/ 
Related to Study 
Procedure? 
Outcome/ 
Withdraw due to 
AE? 
SAE: Criteria?/ 
Severity 
Location to Treatment 
Area/ 
Relationship to Study 
Medication 
Action Taken / 
Other Action 
Taken  
 
XX-XXX 1 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Yes / 1 
DDMMMYYYY(XX) –  
DDMMMYYYY(XX) 
No/No 
XXXXXXXX/ 
Yes 
Yes: 
Hospitalization / 
Mild 
Inside treatment area/ 
Definitely Related 
XXXXXXXX /  
XXXXXXXX 
 
2 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
No / NA 
DDMMMYYYY(XX) –  
Ongoing 
No/Yes 
XXXXXXXX/ 
No 
No/ 
XXXXXXXX 
Outside treatment area/ 
XXXXXXXX  
XXXXXXXX /  
XXXXXXXX 
 
XX-XXX 1 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Yes / 2 
DDMMMYYYY(XX) –  
DDMMMYYYY(XX) 
No/No 
XXXXXXXX/ 
XX 
No/ 
XXXXXXXX 
Non-cutaneous/ 
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX 
 
 
 
Period 1=Week 1-4; Period 2=Post Week4. 
[1] A treatment-emergent AE (TEAE) is defined as an AE with a start date on or after the first application to trial medication. 
[2] Study day is calculated relative to date of first application of study drug (Day 1). 
Generated on  XX/XX/XX:XXXX  by LSTAE / Uses: AE 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 75 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.7.2: Serious Adverse Events  
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
AE 
# 
MedDRA SOC Term/ 
MedDRA Preferred 
Term / 
(Verbatim Term)  
TEAE? [1] / Period 
Onset Date (Day) –  
End Date (Day) [2] 
Related to 
Cosyntropin?/ 
Related to Study 
Procedure? 
Outcome/ 
Withdraw due to 
AE? 
SAE Criteria/ 
Severity 
Location to Treatment 
Area/ 
Relationship to Study 
Medication 
Action Taken / 
Other Action 
Taken  
 
XX-XXX 1 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Yes / 1 
DDMMMYYYY(XX) –  
DDMMMYYYY(XX) 
No/No 
XXXXXXXX/ 
Yes 
Hospitalization / 
Mild 
Inside treatment area/ 
Definitely Related 
XXXXXXXX /  
XXXXXXXX 
 
XX-XXX 2 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
No / NA 
DDMMMYYYY(XX) –  
DDMMMYYYY(XX) 
No/No 
XXXXXXXX/ 
No 
XXX/ 
XXXXXXXX 
Non-cutaneous/ 
XXXXXXXX 
XXXXXXXX /  
XXXXXXXX 
 
 
 
Period 1=Week 1-4; Period 2=Post Week4. 
[1] A treatment-emergent AE (TEAE) is defined as an AE with a start date on or after the first application to trial medication. 
[2] Study day is calculated relative to date of first application of study drug (Day 1). 
Generated on  XX/XX/XX:XXXX  by LSTAE / Uses: AE 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 76 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.7.3: Adverse Events Leading to Study Drug Discontinuation 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
AE 
# 
MedDRA SOC Term/ 
MedDRA Preferred 
Term / 
(Verbatim Term)  
TEAE? [1] / Period 
Onset Date (Day) –  
End Date (Day) [2] 
Related to 
Cosyntropin?/ 
Related to Study 
Procedure? 
Outcome/ 
Withdraw due to 
AE? 
SAE: Criteria?/ 
Severity 
Location to Treatment 
Area/ 
Relationship to Study 
Medication 
Other Action 
Taken  
 
XX-XXX 1 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Yes / 1 
DDMMMYYYY(XX) –  
DDMMMYYYY(XX) 
No/No 
XXXXXXXX/ 
Yes 
Yes: 
Hospitalization / 
Mild 
Inside treatment area/ 
Definitely Related 
XXXXXXXX 
 
2 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
No / NA 
DDMMMYYYY(XX) –  
Ongoing 
No/Yes 
XXXXXXXX/ 
No 
No/ 
XXXXXXXX 
Outside treatment area/ 
XXXXXXXX  
XXXXXXXX 
 
XX-XXX 1 
XXXXXXXX /  
XXXXXXXX  /  
(XXXXXXXX) 
Yes / 2 
DDMMMYYYY(XX) –  
DDMMMYYYY(XX) 
No/No 
XXXXXXXX/ 
XX 
No/ 
XXXXXXXX 
Non-cutaneous/ 
XXXXXXXX 
XXXXXXX 
 
 
 
Period 1=Week 1-4; Period 2=Post Week4. 
[1] A treatment-emergent AE (TEAE) is defined as an AE with a start date on or after the first application to trial medication. 
[2] Study day is calculated relative to date of first application of study drug (Day 1). 
Generated on  XX/XX/XX:XXXX  by LSTAE / Uses: AE 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 77 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.8.1: Urine Pregnancy Test 
All Randomized Female Subjects with Childbearing Potential 
[MC2-01 Cream][Active Comparator] 
 
  
 
 
Subject  
Number 
Birth Control Methods 
Visit 
Date of Test (Day)[1] 
Result 
 
 
 
 
 
 
 
XX-XXX 
Abstinence 
Screening 
DDMMMYYYY(XX)  
Negative 
 
 
 
Visit 1/Day 0 
DDMMMYYYY(XX) 
Negative 
 
 
 
Visit 3/Week 4 
DDMMMYYYY(XX) 
Negative 
 
 
 
Visit 5/Week 8 
DDMMMYYYY(XX) 
Negative 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XX 


MC2 Therapeutics                                                                                                                                                                                        Page 78 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.8.2.X: Clinical Laboratory Test 
[Biochemistry][Hematology] 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Date (Day) and Time of Sample[1] 
Parameter (Unit) 
Reference Range 
Results  
Abnormality 
CFBL 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
DDMMMYYYY (XX)THH:MM 
XXXX 
XXXX,XXXX 
XX.XX 
 
-- 
 
 
 
XXXX 
XXXX,XXXX 
XX.XX 
High 
-- 
 
 
 
XXXX 
XXXX,XXXX 
XX.XX 
 
XXX.X 
 
Visit 3/Week 4 
DDMMMYYYY (XX) 
XXXX 
XXXX,XXXX 
XX.XX 
Low 
XXX.X 
 
Visit 4/Week 8 
DDMMMYYYY (XX) 
XXXX 
XXXX,XXXX 
XX.XX 
 
XXX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFBL = Change from Baseline  
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 79 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.8.2.3: Clinical Laboratory Test 
24 Hour Urinalysis 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Collection Date and Time 
Start – Stop 
Total Volume 
Collected (mL) 
Parameter 
(Unit) 
Reference Range 
Results  
Abnormality 
CFBL 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
DDMMYYYY(DD)THH:MM- 
DDMMYYYY(DD)THH:MM 
XXXX 
XXXX 
XXXX,XXXX 
XX.XX 
 
-- 
 
 
 
 
XXXX 
XXXX,XXXX 
XX.XX 
High 
-- 
 
 
 
 
XXXX 
XXXX,XXXX 
XX.XX 
 
XXX.X 
 
Visit 3/Week 4 
 
 
XXXX 
XXXX,XXXX 
XX.XX 
Low 
XXX.X 
 
Visit 4/Week 8 
 
 
XXXX 
XXXX,XXXX 
XX.XX 
 
XXX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFBL = Change from Baseline  
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
[Programming Note: Week 4 and Week 8 only applies to MC2-01 Cream subjects] 
 


MC2 Therapeutics                                                                                                                                                                                        Page 80 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.8.3: Laboratory Values Outside of Normal Range 
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
Subject Number 
Visit 
Date (Day) of Sample[1] 
Category 
Parameter (Unit) 
Reference Range 
Results  
Abnormality 
CFBL 
 
 
 
 
 
 
 
 
 
XX-XXX 
Visit 1/Day 1 
DDMMMYYYY (XX) 
Biochemistry 
XXXX 
XXXX,XXXX 
XX.XX 
High 
-- 
 
 
 
Hematology 
XXXX 
XXXX,XXXX 
XX.XX 
High 
-- 
 
 
 
Urinalysis 
XXXX 
XXXX,XXXX 
XX.XX 
 
XXX.X 
 
Visit 3/Week 4 
DDMMMYYYY (XX) 
 
XXXX 
XXXX,XXXX 
XX.XX 
Low 
XXX.X 
 
Visit 4/Week 8 
DDMMMYYYY (XX) 
 
XXXX 
XXXX,XXXX 
XX.XX 
 
XXX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CFBL = Change from Baseline  
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 81 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.8.4: Vital Signs  
All Randomized Subjects 
[MC2-01 Cream][Active Comparator] 
 
 
 
 
 
SBP  (mmHg) 
DBP (mmHg) 
Pulse Rate (bpm) 
Subject 
Number 
Visit 
Visit Date (Day) [1] 
 
Observed 
CFBL 
Observed 
CFBL 
Observed 
CFBL 
 
 
 
 
 
 
 
 
 
 
XX-XXX 
Screening 
DDMMYYYY (XX) 
 
XX.X 
-- 
XX.X 
-- 
XX.X 
-- 
 
Visit 1/Day 1 
DDMMYYYY (XX) 
 
XX.X 
-- 
XX.X 
-- 
XX.X 
-- 
 
Visit 2/Week 2 
DDMMYYYY (XX) 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Visit 3/Week 4 
DDMMYYYY (XX) 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Visit 4/Week 6 
DDMMYYYY (XX) 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
Visit 5/Week 8 
DDMMYYYY (XX) 
 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
XX.X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
    
Note: SBP=Systolic blood pressure; DBP=Diastolic blood pressure; CFBL= change from baseline 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXX / Uses: XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 82 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.8.5: Physical Examination 
Randomized Subjects with Abnormal Results 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Visit 
Visit Date (Day) [1] 
Findings 
 
 
 
 
 
 
XX-XXX 
Screening 
DDMMMYYYY (XX) 
Abnormal Not Clinically Significant 
 
 
 
 
 
 
XX-XXX 
XXXX 
DDMMMYYYY (XX) 
Abnormal Clinically Significant  
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XXXX 
 
 
 


MC2 Therapeutics                                                                                                                                                                                        Page 83 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
Data Listing 16.2.8.6: 12-Lead ECG Results 
All Randomized Subjects 
 [MC2-01 Cream][Active Comparator] 
 
 
 
 
 
Subject  
Number 
 Visit 
Visit Date (Day) [1] 
 
ECG Test (Units) 
Result 
 
  
 
 
 
 
XX-XXX 
 Visit 1/Day 1 
DDMMMYYYY (XX) 
 
Interpretation 
Abnormal Not Clinically Significant 
 
  
DDMMMYYYY (XX) 
 
ECG Finding 1 
XXXXX 
 
  
DDMMMYYYY (XX) 
 
ECG Finding 2 
XXXX 
 
 
 
 
 
Summary (Mean) Heart Rate (beats/min) 
 
 
 
 
 
 
Summary (Mean) RR Duration (msec) 
 
 
 
 
 
 
Etc. 
 
 
 
 
 
 
 
 
 
 Visit 3/Week 4 
DDMMMYYYY (XX) 
 
XXXXX 
XXXXX 
 
 Visit 5/Week 8 
DDMMMYYYY (XX) 
 
XXXXX 
XXXXX 
 
 
 
 
 
 
 
 
[1] Study day is calculated relative to date of first application of study drug (Day 1). 
 
Generated on  XX/XX/XX:XXXX  by LSTEG/ Uses: XXXX 


MC2 Therapeutics                                                                                                                                                                                        Page 84 of 84 
Protocol No. MC2-01-C3                                                                                                                                                                  September 20, 2018 
Novella No. NYA14539 
MC2 Therapeutics                                                                                                                                                                                                                                           Page X of Y 
Protocol Number: MC2-01-C3 
 
Data Listing 16.2.9: General Comments 
[MC2-01 Cream][Active Comparator] 
 
Subject 
Number 
Comment Reference 
 
Comment 
XX-XXX 
Visit 3/Week 4 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
  
XX-XXX 
Visit 5/Week 8 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX 
 
 
 
 
 
 
 
 
  
 
Generated on  XX/XX/XX:XXXX  by XXXXX / Uses: XX 
 
 
 


Certificate Of Completion
Envelope Id: C72CEACD45E649FEBAEF9862708CB5E6
Status: Completed
Subject: Please DocuSign: MC2-01-C3 SAP 21sep2018 Amendment 1_clean.pdf
Source Envelope: 
Document Pages: 84
Signatures: 2
Envelope Originator: 
Certificate Pages: 5
Initials: 0
jin Wei
AutoNav: Enabled
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Time Zone: (UTC-05:00) Eastern Time (US & Canada)
1700 Perimeter Park Drive
Morrisville, NC  27560
Jin.Wei2@novellaclinical.com
IP Address: 192.69.83.249  
Record Tracking
Status: Original
             9/21/2018 11:36:32 AM
Holder: jin Wei
             Jin.Wei2@novellaclinical.com
Location: DocuSign
Signer Events
Signature
Timestamp
Carol Udell
Carol.Udell@novellaclinical.com
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Sent: 9/21/2018 11:40:43 AM
Viewed: 9/21/2018 12:13:46 PM 
Signed: 9/21/2018 12:15:46 PM
Electronic Record and Signature Disclosure: 
      Accepted: 6/29/2017 9:05:59 AM
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Johan Selmer
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Sent: 9/21/2018 11:40:43 AM
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Signed: 9/21/2018 11:43:37 AM
Electronic Record and Signature Disclosure: 
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      ID: 7622460b-6a54-44da-884b-23e798fe761d
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Birgitte Vestbjerg
bve@mc2therapeutics.com
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Sent: 9/21/2018 11:40:44 AM
Electronic Record and Signature Disclosure: 
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9/21/2018 12:13:47 PM
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9/21/2018 12:15:46 PM
Completed
Security Checked
9/21/2018 12:15:46 PM
Payment Events
Status
Timestamps
Electronic Record and Signature Disclosure


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Electronic Record and Signature Disclosure created on: 1/26/2017 6:16:50 PM
Parties agreed to: Carol Udell, Johan Selmer, Birgitte Vestbjerg


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