Clinical trial NCT03417141
Conditions: Lichen Planopilaris
Keywords: Valchor
Sponsor: Mayo Clinic
Start date: 2018-04-01; Completion date: 2019-08-30
Enrollment: 12 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary objective of this study is to assess the potential effectiveness of once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. The primary measurement of efficacy will be with the Lichen Planopilaris Activity Index (LPPAI) before and after 6 months of treatment. Secondary measures of efficacy will be the mean follicular density, Physician Global assessment (PGA) score, and the Dermatology Quality of Life Index (DQLI) score before and after six months of therapy.

Detailed description:
This is a single arm, open label, exploratory study to evaluate the efficacy of Valchlor in the treatment of LPP. Subjects will be screened by the Department of Dermatology at the Mayo Clinic in Florida outpatient clinic and interested qualified subjects will be consented and offered participation. This study is designed to establish feasibility and proof of concept and will not include randomization or crossover components.

Patients with biopsy proven LPP who have failed one prior topical or systemic therapy with evidence of active disease will be eligible to participate. The presence of active disease will be based on a baseline clinical exam showing perifollicular erythema with scaling. Patients with predominance of end stage scarring hair loss but without significant active erythema will be excluded. Involvement restricted to the frontal scalp is a recognized clinical variant of LPP and is known as frontal fibrosing alopecia (FAA). As the histological features of LPP and FAA are identical, patients with FAA subtype of LPP would also be eligible to participate in the study.

Eligible participants using high-potency topical corticosteroids, intralesional corticosteroids, or oral hydroxychloroquine may enroll but will be required to discontinue use during the study period.

All study participants will apply Valchlor 0.016% gel to involved areas at night. Patients will be instructed to first part the hair away from involved area as needed, limit application to areas with alopecia and erythema, apply 30 minutes after showering or washing, and allow treated areas to dry for 5 to 10 minutes before covering with clothing or going to bed. Participants will be instructed to wash their hands with soap and water after applying Valchlor. Caregivers who assist in application will be instruction to wear disposable nitrile gloves when applying Valchlor and dispose with the household trash. Patients will be instructed to store Valchlor in the refrigerator away from foods at 36°F - 46°F and apply within 30 minutes after removing from refrigeration.

Arms: arm 1: Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Interventions: intervention 1: Mechlorethamine 0.016% Top Gel
Intervention descriptions: intervention 1: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
Valchlor in the Treatment of 
Lichen Planopilaris: A Single 
Arm, Open‐label, Exploratory 
Study 
 
NCT# NCT03417141 
 
11/26/2018 


Valchlor in the treatment of Lichen Planopilaris 
 
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CONFIDENTIAL 
 
 
VALCHLOR IN THE TREATMENT OF LICHEN PLANOPILARIS: 
A SINGLE ARM, OPEN-LABEL, EXPLORATORY STUDY  
 
 
Regulatory Sponsor-
Investigator: 
Jason C. Sluzevich, MD 
 
Study Site Location: 
Mayo Clinic Department of Dermatology 
4500 San Pablo Road 
Jacksonville, FL   
 
 
Funding Sponsor: 
 
Actelion Pharmaceuticals US, Inc. 
5000 Shoreline Court, Suite 200 
San Francisco, CA 94080 
(650)-624-6900 
 
 
Study Product: 
 
 
VALCHLOR® gel 
Protocol Number: (IRBe) 
 
16-006731 
 
IND Number: 
136907-Exempt from IND Regulations 
 
 
 
Final version:  V7: 26 NOV 2018 
Increase of accrual 
 
V6: 05 OCT 2018 
Change to drug application schedule, change to the 
number of drug tubes dispensed at baseline 
 
V5: 02 MAY 2018  
Addition of hair count assessments 
V4: 06 MAR 2018  
Overall study duration changed from calendar dates  
 
 
 
to length of time of patient exposure  
 
V3: 22 FEB 2018  
Pp 21-24; AE definitions clarified and reporting of 
SAEs to Actelion added 
 
V2: 15 SEP 2017    
Clarified Post IRB reviewed version; contraception 
requirements for females updated 
 
V1:  08AUG2017  
 
Initial protocol 
 
 
 
 
 
 


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Table of Contents 
 
STUDY SUMMARY ...................................................................................................................................... 5 
1 
INTRODUCTION ................................................................................................................................. 6 
1.1 
BACKGROUND .................................................................................................................................... 6 
1.2 
INVESTIGATIONAL AGENT .................................................................................................................... 6 
1.3 
PRECLINICAL DATA ............................................................................................................................. 6 
1.4 
CLINICAL DATA TO DATE..................................................................................................................... 7 
1.5 
DOSE RATIONALE................................................................................................................................ 7 
1.6 
RISKS AND BENEFITS ........................................................................................................................... 7 
2 
STUDY OBJECTIVES .......................................................................................................................... 8 
3 
STUDY DESIGN ................................................................................................................................... 9 
3.1 
GENERAL DESCRIPTION ....................................................................................................................... 9 
3.2 
NUMBER OF SUBJECTS ......................................................................................................................... 9 
3.3 
DURATION OF PARTICIPATION .............................................................................................................. 9 
3.4 
PRIMARY STUDY ENDPOINTS .............................................................................................................. 10 
3.5 
SECONDARY STUDY ENDPOINTS ......................................................................................................... 10 
3.6 
PRIMARY SAFETY ENDPOINTS ............................................................................................................ 10 
3.7 
IDENTIFICATION OF SOURCE DATA ...................................................................................................... 10 
4 
SUBJECT SELECTION ENROLLMENT AND WITHDRAWAL ...................................................... 11 
4.1 
INCLUSION CRITERIA ......................................................................................................................... 11 
4.2 
EXCLUSION CRITERIA ........................................................................................................................ 11 
4.3 
SUBJECT RECRUITMENT, ENROLLMENT AND SCREENING ....................................................................... 11 
4.4 
EARLY WITHDRAWAL OF SUBJECTS .................................................................................................... 12 
4.4.1 
When and How to Withdraw Subjects ........................................................................................ 12 
4.4.2 
Data Collection and Follow-up for Withdrawn Subjects .............................................................. 12 
5 
STUDY DRUG .................................................................................................................................... 12 
5.1 
DESCRIPTION .................................................................................................................................... 12 
5.2 
TREATMENT REGIMEN ....................................................................................................................... 13 
5.3 
METHOD FOR ASSIGNING SUBJECTS TO TREATMENT GROUPS ................................................................ 13 
5.4 
PREPARATION AND ADMINISTRATION OF STUDY DRUG ......................................................................... 13 
5.5 
SUBJECT COMPLIANCE MONITORING ................................................................................................... 13 
5.6 
PRIOR AND CONCOMITANT THERAPY .................................................................................................. 13 
5.7 
PACKAGING ...................................................................................................................................... 14 
5.8 
MASKING/BLINDING OF STUDY........................................................................................................... 14 
5.9 
RECEIVING, STORAGE, DISPENSING AND RETURN ................................................................................. 14 
5.9.1 
Receipt of Drug Supplies .......................................................................................................... 14 
5.9.2 
Storage ................................................................................................................................... 14 
5.9.3 
Dispensing of Study Drug ......................................................................................................... 14 
5.9.4 
Return or Destruction of Study Drug ......................................................................................... 15 
6 
STUDY PROCEDURES ...................................................................................................................... 16 
6.1 
VISIT 1 (WEEK 0/BASELINE) ............................................................................................................... 16 
6.2 
VISIT 2 (WEEK 12± 5 DAYS) ............................................................................................................... 16 
6.3 
VISIT 3 (WEEK 24± 5 DAYS) ............................................................................................................... 16 
7 
STATISTICAL PLAN ......................................................................................................................... 18 
7.1 
SAMPLE SIZE DETERMINATION ........................................................................................................... 18 
7.2 
STATISTICAL METHODS ..................................................................................................................... 18 
7.3 
SUBJECT POPULATION(S) FOR ANALYSIS ............................................................................................. 19 


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8 
SAFETY AND ADVERSE EVENTS ................................................................................................... 20 
8.1 
DEFINITIONS ..................................................................................................................................... 20 
8.2 
RECORDING OF ADVERSE EVENTS ....................................................................................................... 22 
8.3 
REPORTING OF SERIOUS ADVERSE EVENTS AND UNANTICIPATED PROBLEMS .......................................... 22 
8.3.1 
Sponsor-Investigator reporting: notifying the Mayo IRB ............................................................. 23 
8.3.2 
Sponsor-Investigator reporting: Notifying the FDA ..................................................................... 23 
8.4 
UNMASKING/UNBLINDING PROCEDURES ............................................................................................. 23 
8.5 
STOPPING RULES ............................................................................................................................... 24 
8.6 
MEDICAL MONITORING ..................................................................................................................... 24 
9 
DATA HANDLING AND RECORD KEEPING .................................................................................. 24 
9.1 
CONFIDENTIALITY ............................................................................................................................. 24 
9.2 
SOURCE DOCUMENTS ........................................................................................................................ 24 
9.3 
CASE REPORT FORMS ........................................................................................................................ 24 
9.4 
RECORDS RETENTION ........................................................................................................................ 25 
10 
STUDY MONITORING, AUDITING, AND INSPECTING ................................................................ 26 
10.1 
STUDY MONITORING PLAN ............................................................................................................ 26 
10.2 
AUDITING AND INSPECTING ........................................................................................................... 26 
11 
ETHICAL CONSIDERATIONS ......................................................................................................... 26 
12 
STUDY FINANCES ............................................................................................................................ 27 
12.1 
FUNDING SOURCE ......................................................................................................................... 27 
12.2 
CONFLICT OF INTEREST ................................................................................................................. 27 
12.3 
SUBJECT STIPENDS OR PAYMENTS .................................................................................................. 27 
13 
PUBLICATION PLAN ....................................................................................................................... 27 
14 
REFERENCES ................................................................................................................................... 27 
15 
ATTACHMENTS ............................................................................................................................... 28 
 
 
 
 
 
 
 
 


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List of Abbreviations 
 
 
LIST OF ABBREVIATIONS 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CRF 
Case Report Form 
DSMB 
Data and Safety Monitoring Board 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
PHI 
Protected Health Information 
PI 
Principal Investigator 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
LPP 
Lichen Planopilaris 
FAA  
 
 
  Frontal Fibrosing Alopecia 
MF 
 
 
 
  Mycosis Fungoides 
 
 
 


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Study Summary 
Title 
Valchlor in the Treatment of Lichen Planopilaris: A Single Arm, Open‐
Label, Exploratory Study 
 
Running Title 
Valchlor in the treatment of Lichen Planopilaris 
 
Protocol Number 
16-006731 
Phase 
Pilot Study 
Methodology 
Open‐Label, Exploratory Study 
Overall Study 
Duration 
14 Months 
Subject Participation 
Duration 
6 months 
Single or Multi-Site  
Single 
Objectives 
To investigate the efficacy of Valchlor in the treatment of LPP. 
Number of Subjects 
20 
Diagnosis and Main 
Inclusion Criteria 
Adults patient with active LPP or FFA 
1) 18 years old or older at time of consent 
2) Biopsy proven diagnosis of LPP or FAA 
Study Product, Dose, 
Route, Regimen 
Valchlor gel, average use one 60 gram tube per month  
Duration of 
Administration 
6 months 
Reference therapy 
Valchlor gel 
Statistical 
Methodology 
The primary endpoint for this study is the LPPAI score. While a 
minimal clinically significant difference for this outcome measure has 
not been established, clinically meaningful treatment responses will 
generate large changes in the LPPAI score given the weightings used in 
the underlying formula. Therefore, the proposed accrual target of twenty 
patients will be adequate for the preliminary data generating purposes of 
an exploratory study. 
 
 
 


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1 Introduction 
 
This document is a protocol for a human research study. This study will be carried out in 
accordance with the protocol, Good Clinical Practice standards, and applicable United States 
government regulations and Mayo Clinic research policies and procedures.  
1.1 
Background 
 
Lichen Planopilaris (LPP) is a form of lymphocyte mediated scarring alopecia. It is a chronic 
condition that predominates in women between the ages of 45‐70. Patients present with discrete 
patches of hair loss with characteristic perifollicular erythema and scale [1]. Diffuse or localized 
scalp involvement may be seen. Disease progression results in irreversible hair loss and has been 
associated with significant impact on quality of life, depression, and anxiety [2]. Successful 
treatment of LPP requires clearance of the lymphocytic inflammation early in the disease course 
to prevent irreversible follicular destruction and permanent hair loss. 
 
Conventional 
topical 
(e.g. 
corticosteroids) 
and 
systemic 
immunosuppressives 
(e.g. 
mycophenolate mofetil) used in the treatment of LPP directly inhibit lymphocytes but generally 
cannot induce clinical remission [3]. Therefore, there remains a critical unmet therapeutic need 
for an alternative topical product to treat LPP. 
1.2 
Investigational Agent 
 
Valchlor, a gel formulation of mechlorethamine, is an alkylating agent with anti-neoplastic and 
anti-inflammatory properties. Each tube of Valchlor contains 0.016% of mechlorethamine which 
is equivalent to 0.02% mechlorethamine HCL.  It is designed for topical application to non-
mucosal skin surfaces. With topical administration, there is no systemic absorption. Valchlor is 
FDA approved for the topical treatment of Stage IA and IB mycosis fungoides (MF) type 
cutaneous T cell lymphoma in patients who have received prior skin‐directed therapy.  
 
1.3 
Preclinical Data 
 
Valchlor induces lymphocyte apoptosis through either direct cytotoxic effects or possibly 
through indirect alterations of the surrounding cytokine milieu. This has been demonstrated for 
neoplastic conditions such as mycosis fungoides as well as for other inflammatory skin disorders 
such as psoriasis [4,5]. Histologically, the lymphocytic inflammation in LPP is confined to the 
upper portion of the hair follicle known as the infundibulum. The superficial nature of this 
lymphocytic inflammation is ideally suited to targeted topical treatment and is also compatible 
with the absorption and penetration kinetics of Valchlor. The gel vehicle of Valchlor is also 
especially ideal for hair bearing scalp application. The distribution of Langerhans cells in the hair 
follicle is greatest in the infundibulum which also corresponds to where the lymphocytic 
inflammation in LPP is the greatest [6]. Valchlor has been shown to deplete resident Langerhans 
cells in the epidermis and has been previously reported to clear cutaneous lesions in Langerhans 
cell histiocytosis [7]. The failure of other systemic immunosuppressives in treating LPP may 


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reflect the fact that none of these agents directly target Langerhans cells, which constitute the 
main resident population of antigen presenting cells in both the epidermis and hair follicles and 
likely are a relevant therapeutic target in the treatment of LPP. Therefore, the multifactorial 
effects of lymphocyte depletion, Langerhans cell death, and cytokine expression alteration 
induced by Valchlor warrant investigation of the therapeutic potential of Valchlor in the 
management of LPP. 
1.4 
Clinical Data to Date 
 
There is no clinical research data regarding the efficacy of Valchlor in the treatment of LPP.  
1.5 
Dose Rationale  
 
The lymphocyte depleting properties of mechlorethamine, the active ingredient of Valchlor, have 
been clinically demonstrated with once daily application in the treatment of other skin disorders. 
The gel delivery vehicle produces immediate liquefaction and rapid drying upon contact which is 
ideal in the hair bearing scalp and helps to ensure application is restricted to the applied area. 
1.6 
Risks and Benefits 
 
The postulated benefits of Valchlor include immunomodulatory effects to induce clinical 
remission through local effects on lymphocyte proliferation and Langerhans cell function. These 
benefits will occur without the toxicities associated with systemic immunosuppression, and 
without the dose-limiting effect of epidermal and dermal atrophy seen with daily high potency 
topical corticosteroid use. 
  
The possible risks associated with Valchlor include: 
1. Flammable Gel.  The gel formulation is an alcohol-based product and is flammable when 
exposed to fire or other flame before completely drying. This risk will be minimized through 
application instruction procedures provided to study participants and the exclusion of smokers in 
the study. 
 
2. Embryo-fetal Toxicity. Toxicity has been demonstrated with systemic administration of 
mechlorethamine, the active ingredient of Valchlor gel. This risk is minimized in that topical 
application of Valchlor is not associated with detectable levels systemic absorption. 
Additionally, pregnant, nursing females, or females planning or actively trying to become 
pregnant will be excluded from the study. All female study participants of child bearing potential 
prior will be screened for pregnancy with urine B-HCG testing at all study visits and will be 
required to use one form of contraception during the study period. 
 
3. Non-Melanoma Skin Cancer.  Retrospective analysis has shown that 2% (3/128) of patients 
receiving Valchlor for the treatment of early stage MF developed non-melanoma skin cancer 
after one year of use. Many of these patients had previously received other treatments known to 
increase skin cancer risk, and thus the absolute risk directly attributable to Valchlor has not been 
established. This risk will be minimized in this study in that patients will have surveillance skin 


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screening at each follow-up visits, a shorter 6 month treatment interval, and once daily 
application versus the BID to TID application utilized in patients with MF. 
 
4.  Mucosal or Eye Injury.  Mechlorethamine, the active ingredient in Valchlor, can cause pain, 
burns, inflammation, photophobia, and blurred vision. Blindness and severe irreversible anterior 
eye injury may also occur.  These risks are highly dependent on both the mechlorethamine 
concentration and delivery vehicle. For this study, the Valchlor formulation of mechlorethamine 
at 0.016% in a gel vehicle would be expected to be result in mild irritant reactions characterized 
by erythema or tearing in cases of accidental ocular and/or mucosal exposure. The concentrations 
producing scarring conjunctivitis or skin vesiculation have been reported to be 1% or higher and 
are far outside the range of concentrations used for medical purposes [8, 9]. Additionally, there 
are no reports in the indexed PubMed literature of mucosal blistering, cutaneous 
blistering/scarring, or permanent ocular injury including blindness with medical range 
concentrations of Mechlorethamine. Mechlorethamine is used in clinical practice in the United 
States for face and scalp site application. In mycosis fungoides, especially the folliculotropic 
variant, multiple case reports have described the use of mechlorethamine application to the face 
and scalp either as a single agent or in combination with high potency corticosteroids with 
excellent tolerability and no adverse mucosal or ocular events [10]. Mechlorethamine application 
to the scalp for Langerhans histiocytosis has also been reported as safe and effective in both the 
pediatric and adult literature [11].  The risk of the mucosal/eye injury is minimized in this study 
given the low concentration of Mechlorethamine utilized; additionally, study participants must 
demonstrate understanding and have the functional capacity to apply the topical Valchlor as 
directed to be enrolled in the study. 
 
5. Dermatitis. Mechlorethamine in liquid, ointment, cream, and gel formation can induce an 
idiosyncratic contact dermatitis producing erythema, pruritus, and scaling to areas of application. 
This is highly treatment responsive to topical corticosteroids and resolves with discontinuation of 
topical application. This risk is minimized in that Valchlor with a gel vehicle has the lowest 
incidence of contact dermatitis of any medical grade formulation and that discontinuation of the 
Valchlor use also results in resolution of the dermatitis. 
 
2 Study Objectives 
 
The primary objective of this study is to assess the potential effectiveness of once daily 
application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. The 
primary measurement of efficacy will be with the Lichen Planopilaris Activity Index (LPPAI) 
before and after 6 months of treatment. Secondary measures of efficacy will be the mean 
follicular density, Physician Global assessment (PGA) score, and the Dermatology Quality of 
Life Index (DQLI) score before and after six months of therapy. 
 
 


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3 Study Design 
3.1 
General Description 
 
This is a single arm, open label, exploratory study to evaluate the efficacy of Valchlor in the 
treatment of LPP.  Subjects will be screened by the Department of Dermatology at the Mayo 
Clinic in Florida outpatient clinic and interested qualified subjects will be consented and offered 
participation. This study is designed to establish feasibility and proof of concept and will not 
include randomization or crossover components.   
 
Patients with biopsy proven LPP who have failed one prior topical or systemic therapy with 
evidence of active disease will be eligible to participate. The presence of active disease will be 
based on a baseline clinical exam showing perifollicular erythema with scaling. Patients with 
predominance of end stage scarring hair loss but without significant active erythema will be 
excluded. Involvement restricted to the frontal scalp is a recognized clinical variant of LPP and is 
known as frontal fibrosing alopecia (FAA). As the histological features of LPP and FAA are 
identical, patients with FAA subtype of LPP would also be eligible to participate in the study. 
 
Eligible participants using high‐potency topical corticosteroids, intralesional corticosteroids, or 
oral hydroxychloroquine may enroll but will be required to discontinue use during the study 
period. 
 
All study participants will apply Valchlor 0.016% gel to involved areas at night, beginning with 
three times a week (Mondays, Wednesdays and Fridays) and increasing to daily application after 
one month, if well tolerated. Patients will be instructed to first part the hair away from involved 
area as needed, limit application to areas with alopecia and erythema, apply 30 minutes after 
showering or washing, and allow treated areas to dry for 5 to 10 minutes before covering with 
clothing or going to bed. Participants will be instructed to wash their hands with soap and water 
after applying Valchlor. Caregivers who assist in application will be instruction to wear 
disposable nitrile gloves when applying Valchlor and dispose with the household trash. Patients 
will be instructed to store Valchlor in the refrigerator away from foods at 36°F - 46°F and apply 
within 30 minutes after removing from refrigeration. 
3.2 
Number of Subjects 
 
Twenty 
 
3.3 
Duration of Participation 
 
Six months 
 
 
 
 
 


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3.4 
Primary Study Endpoints 
 
The primary outcome measure of efficacy will be the percent reduction of baseline Lichen 
Planopilaris Activity Index (LLPAI) score after 6 months of treatment defined as follows. 
 Complete response: LLPAI reduction greater than 85% from baseline score. 
 Partial response: LLPAI reduction of between 25‐85% from baseline score. 
 Non‐response: LLPAI reduction of less than 25% from baseline score. 
 
The Lichen Planopilaris Activity Index (LPPAI) is a standardized validated quantitative measure 
of disease activity [12].  LPPAI score (0‐10) is calculated as follows: (pruritus + pain + 
burning)/3 + (scalp erythema + perifollicular erythema + perifollicular scale)/3 + 2.5 (pull test) + 
1.5 (spreading/2). Symptoms and signs are graded on a 4‐point scale with 0 = absent, 1 = mild, 2 
= moderate, and 3 =severe. Clinical progression and a positive hair pull test are graded 1=yes; 
0=no. 
3.5 
Secondary Study Endpoints 
 
The secondary outcome measures of efficacy at baseline and after 6 months of treatment will 
include: 
 Mean follicular density as assessed using Canfield scalp photography  
 Dermatology Quality of Life Index (DQLI)  score : 10 standardized items measuring 
impact of skin disease rated as 0=not at all/not relevant; 1=a little; 2=a lot; 3=very much  
 Physician Global Assessment (PGA) score : using standardized photography compared to 
the presenting baseline and scored as -1 = worse (no change to erythema with new areas 
of alopecia);  0 = no change; 1 = mild improvement (slight reduction in erythema, 
alopecia not progressive); 2= moderate (moderate reduction in erythema, alopecia not 
progressive); 3  = significant improvement (very mild erythema, alopecia not 
progressive); 4 = clear (no erythema, alopecia not progressive) 
 
3.6 
Primary Safety Endpoints 
 
The primary safety endpoint of this study will be the number of days between unintentional 
mucosal and/or ocular exposure during the study period. 
3.7 
Identification of Source Data 
 
The following source data will be directly recorded on the Case Report Form (CRF): 
 Baseline and interval changes to medical history 
 LLPAI score 
 DQLI score 
 PGA score 
 Screening and documentation of Adverse Events 
 Phototrichograms for hair count using Fotofinder video-epiluminescence microscopy in 
combination with the Trichoscan digital image analysis  


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The following source data will not be directly recorded in the CRF, but will be captured in 
supportive documentation to include study source documents and the EMR: 
 Laboratory results and clinical interpretation of the values 
 Standardized clinical photography 
4 Subject Selection Enrollment and Withdrawal 
4.1 
Inclusion Criteria 
 
Informed subject consent will be obtained from those patients meeting the following inclusion 
criteria: 
 Male and female patients 18 years or older. 
 Biopsy proven diagnosis of Lichen Planopilaris 
 Biopsy proven diagnosis of Fontal Fibrosing Alopecia (a clinical variant of LPP restricted 
to frontal scalp)   
 Good general health as confirmed by medical history 
 Patients who are willing and capable of cooperating to the extent and degree required by 
the protocol; and 
 Patients who read and sign an approved informed consent for this study 
4.2 
Exclusion Criteria 
 
Patients are to be excluded based on the following criteria: 
 Vulnerable study population  
 Pregnant or nursing women  
 Women planning a pregnancy within the study period 
 Active smokers 
 Known history of adverse reaction to mechlorethamine 
 Use of systemic immunosuppressive 
 Presence of ulcerated scalp lesions 
4.3 
Subject Recruitment, Enrollment and Screening 
 
Subjects will be recruited from the Department of Dermatology at the Mayo Clinic in Florida 
outpatient clinical practice. All referring dermatologic physicians to Mayo Clinic Florida in the 
Southeastern United States will also be mailed a notice advising of the availability of this study. 
Patients may be directly referred for participation by these providers with all screening and 
follow-up exams performed at Mayo Clinic in Florida.  Patients will be provided with a Research 
Participant Consent and Privacy Authorization Form describing the study formulation, protocol, 
inclusion and exclusion criteria, as well as risks and benefits of participation.  


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4.4 
Early Withdrawal of Subjects 
4.4.1 When and How to Withdraw Subjects 
 
Patients are free to withdraw at any time and for whatever reason.  No data will be collected for 
withdrawn subjects and withdrawn subjects may be replaced within the accrual period.  There 
will be no follow-up for withdrawn subjects.  Pre-specified reasons for discontinuing include, but 
are not limited to, the following:  
 Patient Request: Patient decided that he/she did not want to continue (for any reason) 
 Adverse Event: Patient experienced a related or unrelated event that would interfere with 
the study objectives/evaluation  
 Lost to Follow-up: Patient did not come in for a visit and could not be reached by phone 
 Treatment Failure: If in the Principal Investigator and/or Investigators’ judgment, the 
patient’s condition required another form of treatment  
 Mechlorethamine sensitization: Patient develops contract dermatitis to Valchlor that 
cannot be managed with low potency topical corticosteroids 
 Inclusion/Exclusion Discrepancy/Violation: Patient should not have been enrolled 
 Noncompliance: Patient is not complying with the protocol requirements (i.e. visit 
schedule, dosing, regimen, etc.); a patient is to be withdrawn if he/she misses two 
consecutive visits  
 Other: Any other reason 
 
4.4.2 Data Collection and Follow-up for Withdrawn Subjects 
 
If a Participant withdraws from the study, no additional attempts will be made to contact the 
Participant. 
5 Study Drug  
5.1 
Description 
 
VALCHLOR is a topical product that contains mechlorethamine HCl, an alkylating drug. 
Mechlorethamine HCl is a white to off white solid that is very soluble in water and methanol, 
partially soluble in acetone, and generally not soluble in organic solvents.  
 
Mechlorethamine 
HCl 
is 
designated 
chemically 
as 
2-chloro-N-(2-chloroethyl)-N-
methylethanamine hydrochloride. The molecular weight is 192.52 and the melting point is 108-
111°C. The empirical formula is C5H11Cl2N•HCl, and the structural formula is: 
CH3N(CH2CH2Cl)2•HCl.  
 
Each tube of VALCHLOR contains 60g of a gel containing 0.016% w/w of mechlorethamine 
(equivalent to 0.02% mechlorethamine HCl) in a base of the following inactive ingredients: 
diethylene glycol monoethyl ether, propylene glycol, isopropyl alcohol, glycerin, lactic acid, 
hydroxypropylcellulose, sodium chloride, menthol, edetate disodium, butylated hydroxytoluene. 
 


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Systemic exposure was undetectable after topical administration of VALCHLOR to patients. 
Blood samples were analyzed from 16 and 15 patients following treatment with VALCHLOR 
(mechlorethamine gel 0.016%) and an identical formulation consisting of mechlorethamine 
0.032% w/w, respectively. For patients who received mechlorethamine 0.016%, samples were 
collected to measure mechlorethamine concentrations prior to dosing, on day 1, and at the first 
month visit. Following the topical administration of mechlorethamine 0.016%, there were no 
detectable plasma mechlorethamine concentrations observed in any of the patients. Patients who 
received mechlorethamine 0.032% had no measurable concentrations of mechlorethamine or 
half-mustard after 2, 4, or 6 months of treatment. 
5.2 
Treatment Regimen 
 
All study participants will apply Valchlor 0.016% gel to involved areas at night, beginning with 
three times a week, (Mondays, Wednesdays and Fridays) and increasing to daily application after 
one month, if well tolerated, for a total of 6 months. Patients will be instructed to first part the 
hair away from involved area as needed, limit application to areas with alopecia and erythema, 
apply 30 minutes after showering or washing, and allow treated areas to dry for 5 to 10 minutes 
before covering with clothing or going to bed. Participants will be instructed to wash their hands 
with soap and water after applying Valchlor. Caregivers who assist in application will be 
instruction to wear disposable nitrile gloves when applying Valchlor and dispose with the 
household trash. Patients will be instructed to store Valchlor in the refrigerator away from foods 
at 36‐46 degrees F and apply within 30 minutes after removing from refrigeration. 
 
5.3 
Method for Assigning Subjects to Treatment Groups 
 
This is an open-label pilot investigation and all study participants are assigned to active treatment 
with a topically applied study drug. There is no placebo arm in this study. 
5.4 
Preparation and Administration of Study Drug 
 
The study drug will be stored and dispensed to patients at each study visit from the Mayo Clinic 
Florida Research Pharmacy.  
5.5 
Subject Compliance Monitoring 
 
Study participants will be dispensed one 60 gram tube at the qualifying baseline exam, 2 tubes at 
week 4 following phone visit, and 3 tubes at the week 12 follow-up visit. They will be instructed 
to use one tube per 30 days and be will instructed to bring these tubes for all follow-up visits. 
Weights of each tube after 30 days of use will be recorded.  
5.6 
Prior and Concomitant Therapy 
 
Eligible participants using high‐potency topical corticosteroids, intralesional corticosteroids, or 
oral hydroxychloroquine may enroll but will be required to discontinue use during the 6 month 
study duration. 


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Mild irritant reactions at site application may be treated with class IV topical corticosteroids in a 
gel vehicle the morning following nightly application on an as needed basis. 
5.7 
Packaging 
 
Each tube of VALCHLOR contains 60g of a gel containing 0.016% w/w of mechlorethamine 
(equivalent to 0.02% mechlorethamine HCl) in a base of the following inactive ingredients: 
diethylene glycol monoethyl ether, propylene glycol, isopropyl alcohol, glycerin, lactic acid, 
hydroxypropylcellulose, sodium chloride, menthol, edetate disodium, butylated hydroxytoluene. 
 
Study drug will be shipped to the Mayo Clinic research pharmacy in Florida and labeled upon 
receipt with statement “Caution: New Drug Limited by Federal law for investigational use.”  
5.8 
Masking/Blinding of Study  
 
This is an open-label pilot investigation.  Masking and blinding procedures are not applicable.  
Qualitative and quantitative evaluations of response to treatment will be recorded.  Updated 
photographs will be included in participants’ records at each visit. 
5.9 
Receiving, Storage, Dispensing and Return 
5.9.1 Receipt of Drug Supplies 
 
The drug will be shipped by Actelion Pharmaceuticals US, Inc to the Mayo Clinic research 
pharmacy in Florida.  Upon receipt of the of the study drug, an inventory will be performed and a 
drug receipt log filled out by the person accepting the shipment.  Designated study staff will 
count and verify that the shipment contains all the items noted in the shipping invoice. Any 
discrepancies, damaged or unusable study drug in a given shipment will be documented in the 
study files. The sponsor-investigator must be notified immediately of any discrepancies, 
damaged or unusable products that are received. 
5.9.2 Storage 
 
Prior to dispensing, Valchlor will be stored in the freezer at -13°F to 5°F (-25°C to -15°C). After 
dispensing, patients will be advised to store Valchlor in a refrigerator at 36°F - 46°F (2°C - 8°C). 
Patients should consult a pharmacist prior to using Valchlor that has been left at room 
temperature for longer than one hour per day. 
5.9.3 Dispensing of Study Drug 
 
Regular study drug reconciliation will be performed to document drug assigned, drug dispensed, 
drug returns, and drug remaining.  This reconciliation will be logged on the drug reconciliation 
form, and signed and dated by the study team. Drug dispensation will occur at scheduled follow-
up visits. 


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5.9.4 Return or Destruction of Study Drug 
 
At the completion of the study, there will be a final reconciliation of drug shipped, drug 
dispensed, drug returns, and drug remaining.  This reconciliation will be logged on the drug 
reconciliation form, signed and dated.  Any discrepancies noted will be documented and 
investigated, prior to return or destruction of unused study drug.  Remaining drug will be 
destroyed on site will be documented in the study files. Participants will be required to return any 
unused study drug at the end of the study period.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6 Study Procedures 
6.1 
Visit 1 (Week 0/Baseline) 
 
a) Informed consent 
b) Review treatment protocol 
c) LPPAI baseline score 
d) PGA baseline score 
e) DLQI baseline score  
f) Review medical history and current medications  
g) Baseline photographs 
h) Assessments of hair density using phototrichograms 
i) Dispense 1 tube of study drug  
j) Urine Pregnancy Test (female patients of childbearing potential); start/confirm form of 
contraception 
 
6.2     Visit 2 (Week 4 Phone Follow-up) 
 
a) Phone follow-up visit to assess any adverse reactions (if any) 
b) Dispense 2 tubes of study drug 
6.2 
Visit 3 (Week 12± 5 days) 
 
a) LPPAI score 
b) Review changes to medical history and current medications 
c) Screen/Review adverse events  
d) Repeat photographs  
e) Assessments of hair density using phototrichograms  
f) Dispense 3 tubes and reconcile study drug 
g) Review compliance  
h) Urine Pregnancy Test (female patients of childbearing potential); confirm form of 
contraception 
6.3 
Visit 4 (Week 24± 5 days) 
 
a) LPPAI score final 
b) PGA score final 
c) DLQI score final 
d) Review changes to medical history and current medications 
e) Screen/review adverse events  
f) Repeat photographs 
g) Assessments of hair density using phototrichograms   
h) Reconcile and collection of unused study drug 
i) Urine Pregnancy Test (female patients of childbearing potential); confirm form of 
contraception 
 


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Schedule of Events 
Study Activity 
Day 
1 
SCREENING 
BASELINE  
Week 4 
PHONE 
FOLLOW-
UP 
Week 
12 
FOLLOWUP 
Week 
24 
FOLLOWUP 
Visit Number     
1 
2 
3 
4 
Allowable visit window in days 
 
+/- 5 
+/- 5  
+/- 5  
Review Eligibility 
X 
 
 
 
Informed Consent 
X 
 
 
 
Medical History 
X 
 
 
 
Dispense/Reconcile Medications  
X 
X 
X 
X 
Review Changes to Med 
History and Medications 
 
 
X 
X 
LPPAI 
X 
 
X 
X 
PGA 
X 
 
 
X 
DLQI 
X 
 
 
X 
B-HCG (females) 
X 
 
X 
X 
Photographs/Hair Count 
X 
 
X 
X 
Review Valchlor Application 
Instructions 
X 
 
X 
X 
Screening for Adverse Events 
 
X 
X 
X 
 
 
 
 
 
 


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7 Statistical Plan 
7.1 
Sample Size Determination 
 
Due to the pilot nature of the study, no formal statistical power or sample size calculations are 
necessary.  The sample size of 20 patients will be sufficient for this pilot study to obtain a 
preliminary estimate of treatment efficacy and to generate data that will be useful in the design of 
a larger study. 
7.2 
Statistical Methods 
 
Descriptive Statistics 
 
Continuous variables will be summarized using the sample mean, median, standard deviation, 
interquartile range, and range.  Categorical variables will be summarized using number and 
percentage of patients 
 
Handling of Missing Data 
 
This is a prospective study and therefore we do not anticipate any missing data.  In the event of 
any unexpected missing data, no attempt to impute this missing data will be made; missing data 
will simply be treated as missing in the statistical analysis. 
 
Multiplicity 
 
Since this is an exploratory pilot study, no adjustment for multiple testing is needed.   
 
Primary Hypothesis: 
 
The primary endpoint for this study is the LPPAI score. While a minimal clinically significant 
difference for this outcome measure has not been established, clinically meaningful treatment 
responses will generate large changes in the LPPAI score given the weightings used in the 
underlying formula. Therefore, the proposed minimal accrual target of twenty patients will be 
adequate for the preliminary data generating purposes of an exploratory study. A larger sample 
size to detect smaller changes in the LPPAI score is not needed as small differences in the 
LPPAI score are not clinically meaningful. The minimal accrual target of 10 is achievable given 
an estimated incidence of LPP/FAA of 1‐3% in tertiary hair loss centers. The definitions of 
complete response, partial response, and non‐response will be defined using standardized LLPAI 
scoring which will permit a relative comparison of treatment efficacy to previously published 
systemic treatments using hydroxychloroquine and mycophenolate mofetil.  
 
Interim Analysis 
 
There will not be any interim analysis given the low risk profile of the study formulation. 


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7.3 
Subject Population(s) for Analysis 
 
Each participant who received the study drug will be included in the primary analysis regardless 
of study withdrawal for any reason. In the event of any study withdrawals, in secondary analysis 
we will examine the sensitivity of our results to the exclusion of patients who withdrew. 
 
 
 
 
 


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8 Safety and Adverse Events 
8.1 
Definitions 
Unanticipated Problems Involving Risk to Subjects or Others (UPIRTSO) 
Any unanticipated problem or adverse event that meets the following three criteria:  
 Serious: Serious problems or events that results in significant harm, (which may be 
physical, psychological, financial, social, economic, or legal) or increased risk for the 
subject or others (including individuals who are not research subjects). These include: (1) 
death; (2) life threatening adverse experience; (3) hospitalization - inpatient, new, or 
prolonged; (4) disability/incapacity - persistent or significant; (5) birth defect/anomaly; (6) 
breach of confidentiality and (7) other problems, events, or new information (i.e. 
publications, DSMB reports, interim findings, product labeling change) that in the opinion 
of the local investigator may adversely affect the rights, safety, or welfare of the subjects 
or others, or substantially compromise the research data, AND 
 Unanticipated: (i.e. unexpected) problems or events are those that are not already 
described as potential risks in the protocol, consent document, not listed in the 
Investigator’s Brochure, or not part of an underlying disease. A problem or event is 
"unanticipated" when it was unforeseeable at the time of its occurrence. A problem or 
event is "unanticipated" when it occurs at an increased frequency or at an increased 
severity than expected, AND 
 Related: A problem or event is "related" if it is possibly related to the research procedures. 
 
 
Adverse Event 
An AE is defined as any untoward medical occurrence in a patient administered a pharmaceutical 
product and which does not necessarily have a causal relationship with the treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal lab finding), symptom 
or disease temporally associated with the use of a medicinal product, whether or not related to 
the medicinal product.  
 
Each AE must be assessed by the investigator as to whether or not there is a reasonable 
possibility of causal relationship to Valchlor, and documented as either related or unrelated. The 
determination of the likelihood that Valchlor caused the AE must be provided by an investigator 
who is a qualified physician. .  
 
Initial screening for AE will include non-directed questioning of the patient at each follow-up 
visit during the study period along with the directed questioning and examination regarding:  
 
 Signs and symptoms of idiosyncratic allergic contact dermatitis  
 
Patients will be instructed to stop using Valchlor and to contact the study coordinator if 
swelling and blistering occurs as this may represent early signs of allergic contact dermatitis.  
The primary investigator will then evaluate the patient and if the signs and symptoms are 


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compatible with allergic contract dermatitis, the patient will be offered treatment using a 
medium-potency topical corticosteroid to involved areas in the AM, with resumption of 
Valchlor application in the PM.  Patients with persistent allergic contact dermatitis reactions 
unable to be managed as outlined above will exit the study. 
 
 Unintentional  mucosal and/ocular exposure 
 
Patients will be warned not to apply Valchlor near eyes, mouth, or nose as it can cause pain, 
redness, swelling, burning, sensitivity to light, blurred vision, and blindness or permanent eye 
injury. If accidental Valchlor exposure to nose, mouth or eyes occurs, patients will be 
instructed to rinse affected areas with large amounts of water for 15 minutes and to contact 
the study coordinator. The primary investigator will then contact the patient to review 
application site instructions and schedule a follow-up evaluation if the patient reports 
persistent symptoms or erythema.   
 
Serious Adverse Event 
Adverse events defined as serious will the following:  
 death 
 life threatening adverse experience 
 hospitalization 
 inpatient, new, or prolonged; disability/incapacity 
 persistent or significant disability or incapacity 
 birth defect/anomaly 
 medically significant 
 
Medically Significant: refers to important medical events that may not immediately result in 
death, be life-threatening, or require hospitalization but may be considered to be SAEs when,  
based upon appropriate medical judgment, they may jeopardize the subject, and may require 
medical or surgical intervention to prevent one of the outcomes listed in the definitions above. 
 
All adverse events that do not meet any of the criteria for serious, will be regarded as non-
serious adverse events.  
 
Adverse Event Reporting Period 
For this study, the study treatment follow-up period is defined as the last scheduled visit. 
 
Preexisting Condition 
A preexisting condition is one that is present at the start of the study.  A preexisting condition 
will be recorded as an adverse event if the frequency, intensity, or the character of the condition 
worsens during the study period. 
 
General Physical Examination Findings 
At screening, any clinically significant abnormality should be recorded as a preexisting 
condition.  At the end of the study, any new clinically significant findings/abnormalities that 
meet the definition of an adverse event will also be recorded and documented as an adverse 
event.  


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Post-study Adverse Event 
All unresolved adverse events should be followed by the sponsor-investigator until the events are 
resolved, the subject is lost to follow-up, or the adverse event is otherwise explained.  At the last 
scheduled visit, the sponsor-investigator should instruct each subject to report, to the sponsor-
investigator, any subsequent event(s) that the subject, or the subject’s personal physician, 
believes might reasonably be related to participation in this study.  
 
 
Abnormal Laboratory Values 
Any clinical laboratory abnormality that can reasonably be related to the topical administration 
of Valchlor should be documented as an adverse event. 
 
Hospitalization, Prolonged Hospitalization or Surgery 
Hospitalization, prolonged hospitalization, or surgery is to be reported as an adverse event if it 
can reasonably be related to the topical use of Valchlor. 
8.2 
Recording of Adverse Events 
At each contact with the subject, the study team will seek information on adverse events by 
specific questioning and, as appropriate, by examination.  Information on all adverse events 
should be recorded immediately in the source document, and also in the appropriate adverse 
event section of the case report form (CRF). All clearly clinically related signs, symptoms, and 
abnormal diagnostic, laboratory or procedure results will be recorded in the source document. 
 
All adverse events occurring during the study period will be recorded.  The clinical course of 
each event should be followed until resolution, stabilization, or until it has been ultimately 
determined that the study treatment or participation is not the probable cause.  Serious adverse 
events that are still ongoing at the end of the study period must be followed up, to determine the 
final outcome.  Any serious adverse event that occurs during the Adverse Event Reporting 
Period and is considered to be at least possibly related to the study treatment or study 
participation should be recorded and reported to Actelion immediately (see 8.3 below). 
8.3 
Reporting of Serious Adverse Events and Unanticipated Problems 
 
When an adverse event has been identified, the study team will take appropriate action necessary 
to protect the study participant and then complete the Study Adverse Event Worksheet and log.  
The sponsor-investigator will evaluate the event and determine the necessary follow-up and 
reporting required. All SAEs considered possibly as related to study medication by the Sponsor-
Investigator must be reported immediately to Actelion Global Drug Safety (GDS) as set forth in 
the IIS agreement (on Actelion SAE template FRM-001093). Actelion reserves the right to 
request additional information and clarifications on cases forwarded by the Sponsor-Investigator. 
 
North America (US and Canada) 
San Francisco, USA 
DrugsafetyUS@actelion.com 
Fax: 1-866-227-5886 


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8.3.1 Sponsor-Investigator reporting: notifying the Mayo IRB 
 
The Principal Investigator and/or Investigators will report, as soon as possible, but no later than 5 
working days after first learning of the problem/event, to the Mayo Clinic IRB any UPIRTSOs 
and Non-UPIRTSOs according to the Mayo Clinic IRB Policy and Procedures. 
 
Documentation of adverse events will include the following information collected in the adverse 
event section of the case report form (and entered into the research database):  
 Subject’s name:  
 Medical record number:  
 Disease:  
 The date the adverse event occurred:  
 Description of the adverse event:  
 Relationship of the adverse event to the research:  
 If the adverse event was expected:  
 The severity of the adverse event (defined by a severity scale): 
 If any intervention was necessary:  
 Resolution (was the incident resolved spontaneously, or after discontinuing treatment): 
 Date of Resolution:  
 
The Principal Investigator and/or Investigators will review all adverse event reports to determine 
if specific reports need to be made to the IRB, FDA and Actelion.  The Principal Investigator 
and/or Investigators will sign and date the adverse event report when it is reviewed.  For this 
protocol, only directly related SAEs/UPIRTSOs will be reported to the IRB. 
8.3.2 Sponsor-Investigator reporting: Notifying the Actelion 
 
This protocol is not being conducted under an FDA investigational new drug application.  
  
Any AE reports meeting reporting criteria obligation (serious and possibly related to Valchlor) 
need to be reported to Actelion immediately.  
 
Actelion Global Drug Safety will report any safety information received from SPONSOR-
INVESTIGATOR to the competent Health Authorities as per regulatory reporting requirements 
regarding marketed products. 
 
Additionally, if any AE or actions taken for safety reasons are sent directly to FDA by 
SPONSOR-INVESTIGATOR, copy of the same notification must also be sent in copy 
immediately to Actelion with clear notation regarding FDA notification. 
 
8.4 
Unmasking/Unblinding Procedures 
 
This is an open-label pilot investigation. Unmasking and unblinding procedures are not 
applicable.  


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8.5 
Stopping Rules  
 
This investigation is of low risk to study subjects.  Stopping or interruption of the study may be 
necessary if a significant number of participants develop an unexpectedly high incidence of 
contact dermatitis that cannot be managed with low potency topical steroids. 
8.6 
Medical Monitoring 
It is the responsibility of the Principal Investigator to oversee the safety of the study at his/her 
site.  This safety monitoring will include careful assessment and appropriate reporting of adverse 
events as noted above, as well as the construction and implementation of a site data and safety-
monitoring plan (see section 10  “Study Monitoring, Auditing, and Inspecting”).  Medical 
monitoring will include a regular assessment of the number and type of serious adverse events. 
9 Data Handling and Record Keeping 
9.1 
Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected from subjects in this study 
 Who will have access to that information and why 
 Who will use or disclose that information 
 The rights of a research subject to revoke their authorization for use of their PHI  
 
In the event that a subject revokes authorization to collect or use PHI, the Principal Investigator 
and Investigators, by regulation, retain the ability to use all information collected prior to the 
revocation of subject authorization.  For subjects that have revoked authorization to collect or 
use PHI, attempts will be made to obtain permission to collect at least vital status (long term 
survival status that the subject is alive) at the end of their scheduled study period. 
9.2 
Source Documents 
Source data is all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial.  Source 
data are contained in source documents.  Examples of these original documents, and data records 
include: hospital records, clinical and office charts, laboratory notes, memoranda, subjects’ 
diaries or evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies or transcriptions certified after verification as being accurate and complete, 
microfiches, photographic negatives, microfilm or magnetic media, x-rays, subject files, and 
records kept at the pharmacy, at the laboratories, and at medico-technical departments involved 
in the clinical trial. 
9.3 
Case Report Forms 
All data requested on the Case Report Form (CRF) will be recorded for each participant.  A 
standardized CRF will be generated by REDCap.  All missing data will be explained.  If a space 
on the CRF is left blank because the question was not asked, “N/D” will be recorded.  If the item 
is not applicable to the individual case, “N/A” will be recorded.  All entries will be printed 


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legibly in black ink.  If any entry error has been made, a single straight line through the incorrect 
entry will be drawn and the correct data will be written above it.  All such changes will be 
initialed and dated.  Errors will not be erased or whited-out.  For clarification of illegible or 
uncertain entries, a clarification will be printed above the item, then initialed and dated.  If the 
reason for the correction is not clear or needs additional explanation, details to justify the 
correction will be neatly included. 
 
Data Management 
 
Study data to be collected and managed using REDCap electronic data capture tools hosted at the 
Mayo Clinic.  REDCap (Research Electronic Data Capture) is a secure, web-based application 
designed to support data capture for research studies, providing 1) an intuitive interface for 
validated data entry; 2) audit trails for tracking data manipulation and export procedures; 3) 
automated export procedures for seamless data downloads to common statistical packages; and 
4) procedures for importing data from external sources. 
 
Data Processing 
 
All study date will be stored and analyzed at Mayo Clinic in Florida.  
 
Data Security and Confidentiality 
 
All source documents including clinical findings, observations or other activities will be stored in 
a REDCap database that will be designed by the Statistician.  Access to the REDCap database 
will be limited to the Principal Investigator, Investigators, and Statistician. 
 
 
Data Quality Assurance 
 
Once the study is completed the Principal Investigator will randomly select 3 participants and 
compare the data documented for each on the CRF with what is entered into the REDCap 
database.  If there is any discrepancy, the Principal Investigator and/or Investigators will cross-
reference all 20 patients to ensure accuracy.  
 
Data Clarification Process 
 
For any data query the Principal Investigator and Investigators will meet to clarify the data 
queried and make corrections based on consensus.  
9.4 
Records Retention 
The sponsor-investigator will maintain records and essential documents related to the conduct of 
the study.  These will include subject case histories and regulatory documents. 
 
The sponsor-investigator will retain the specified records and reports for; 
1. Up to 2 years after the marketing application is approved for the drug; or, if a marketing 
application is not submitted or approved for the drug, until 2 years after shipment and 


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delivery of the drug for investigational use is discontinued and Actelion has been so 
notified. OR 
2. As outlined in the Mayo Clinic Research Policy Manual –“Retention of and Access to 
Research Data Policy” and as outlined in the Actelion Investigator Initiated Study 
Agreement. 
10 Study Monitoring, Auditing, and Inspecting 
10.1 Study Monitoring Plan 
 
The investigator will allocate adequate time for such monitoring activities.  The Investigator will 
also ensure that the monitor or other compliance or quality assurance reviewer is given access to 
all the study-related documents and study related facilities (e.g. pharmacy, diagnostic laboratory, 
etc.), and has adequate space to conduct the monitoring visit. 
10.2 Auditing and Inspecting 
 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, the 
sponsor, and government regulatory agencies, of all study related documents (e.g. source 
documents, regulatory documents, data collection instruments, study data etc.).  The investigator 
will ensure the capability for inspections of applicable study-related facilities (e.g. pharmacy, 
diagnostic laboratory, etc.). 
 
Participation as an investigator in this study implies acceptance of potential inspection by 
government regulatory authorities and applicable compliance offices. 
11 Ethical Considerations 
This study is to be conducted according to United States government regulations and 
Institutional research policies and procedures. 
 
This protocol and any amendments will be submitted to a properly constituted local Institutional 
Review Board (IRB), in agreement with local legal prescriptions, for formal approval of the 
study.  The decision of the IRB concerning the conduct of the study will be made in writing to 
the sponsor-investigator before commencement of this study. 
 
All subjects for this study will be provided a consent form describing this study and providing 
sufficient information for subjects to make an informed decision about their participation in this 
study.  This consent form will be submitted with the protocol for review and approval by the IRB 
for the study.  The formal consent of a subject, using the Approved IRB consent form, must be 
obtained before that subject undergoes any study procedure.  The consent form must be signed 
by the subject or the subject’s legally authorized representative, and the individual obtaining the 
informed consent. This study will not include vulnerable study populations. 
 


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12 Study Finances 
12.1 Funding Source 
 
This investigator initiated study is funded by Actelion Pharmaceuticals. 
12.2 Conflict of Interest 
 
Any study team member who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, etc.) must 
have the conflict reviewed by a properly constituted Conflict of Interest Committee with a 
Committee-sanctioned conflict management plan that has been reviewed and approved by the 
study sponsor-investigator prior to participation in this study. 
 
No financial conflicts of interested are anticipated for this study. 
12.3 Subject Stipends or Payments 
 
No payment is given to study participants. 
13 Publication Plan 
 
The primary responsibility for publication of the study results is with the Primary Investigator. 
After the complication of study and prior to publication, the study results will be shared with 
Actelion Pharmaceuticals. The study will be registered at ClinicalTrials.gov prior to subject 
recruitment along with the posting of the results within 12 months of final data collection for the 
primary outcome measure.  
14 References 
 
[1] Somani N1, Bergfeld WF. Cicatricial alopecia: classification and histopathology. Dermatol 
Ther. 2008 Jul‐Aug;21(4):221‐37. 
[2] Chiang YZ, Bundy C, Griffiths CE, Paus R, Harries MJ. The role of beliefs: lessons from a 
pilot study on illness perception, psychological distress and quality of life in patients with 
primary cicatricial alopecia. Br J Dermatol. 2015;172(1):130‐137. 
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