Valchlor in the Treatment of Lichen Planopilaris

• Sponsor: Mayo Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT03417141
• Collaborator: Actelion (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 17
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lichen Planopilaris	Drug: Mechlorethamine 0.016% Top Gel	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Adults patient with active Lichen Planopilaris or Frontal Fibrosing AlopeciaAdults patient with active Lichen Planopilaris or Frontal Fibrosing Alopecia
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Valchlor in the Treatment of Lichen Planopilaris: A Single Arm, Open- Label, Exploratory Study
• Actual Study Start Date: Apr 1, 2018
• Actual Primary Completion Date: Aug 30, 2019
• Actual Study Completion Date: Aug 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Valchor treatment of Lichen Planopilaris Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.	Drug: Mechlorethamine 0.016% Top Gel; Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.; Other Names: Valchlor

Outcome Measures

Primary Outcome Measures

1. Change in Lichen Planopilaris Activity Index (LLPAI) [baseline, up to 24 weeks]

   The Lichen Planopilaris Activity Index is a standardized validated quantitative measure of disease activity. 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. The percent change of LLPAI score from before and after treatment.

Secondary Outcome Measures

1. Change in Dermatology Quality of Life Index (DQLI) [baseline, 24 weeks]

   The DQLI is 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. The absolute change of total DQLI score from before and after treatment

2. Change in Follicular Units [baseline, 24 weeks]

   Phototrichograms of all subjects scalps performed using FotoFinder video-epiluminescence microscopy (FotoFinder Systems GmbH) in combination with TrichoScan digital image analysis (TRICHOLOG GmbH and DatInf mbH). The percent change in the total number of hairs per square cm was measured before and after treatment.

3. Change in Mean Follicular Density [baseline, 24 weeks]

   Phototrichograms of all subjects scalps performed using FotoFinder video-epiluminescence microscopy (FotoFinder Systems GmbH) in combination with TrichoScan digital image analysis (TRICHOLOG GmbH and DatInf mbH). The percent change in the mean number of follicular units per square cm was measured before and after treatment.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Exclusion 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic in Florida	Jacksonville	Florida	United States	32224

Sponsors and Collaborators

• Mayo Clinic
• Actelion

Investigators

• Principal Investigator: Jason Sluzevich, MD, Mayo Clinic

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 26, 2018

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Jason Sluzevich MD, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT03417141
• Other Study ID Numbers: IRB 16-006731
• First Posted: Jan 31, 2018
• Last Update Posted: Jan 28, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jason Sluzevich MD, Principal Investigator, Mayo Clinic: Valchor
• Additional relevant MeSH terms: Lichen Planus; Mechlorethamine

Study Results

Participant Flow

Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Period Title: Overall Study
STARTED	12
COMPLETED	8
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Overall Participants	12
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	66
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 91.7%
More than one race	0 0%
Unknown or Not Reported	1 8.3%
Region of Enrollment (participants) [Number]
United States	12 100%
LICHEN PLANOPILARIS ACTIVITY INDEX (LPPAI) (Integer) [Median (Full Range) ]
Median (Full Range) [Integer]	5

Outcome Measures

1. Primary Outcome

Title	Change in Lichen Planopilaris Activity Index (LLPAI)
Description	The Lichen Planopilaris Activity Index is a standardized validated quantitative measure of disease activity. 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. The percent change of LLPAI score from before and after treatment.
Time Frame	baseline, up to 24 weeks

Outcome Measure Data

Analysis Population Description

One subject withdrew and data was not analyzed for that subject

Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Measure Participants	11
Week 12	-42.9
Week 24	-66.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Valchor Treatment of Lichen Planopilaris
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.014
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Valchor Treatment of Lichen Planopilaris
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Secondary Outcome

Title	Change in Dermatology Quality of Life Index (DQLI)
Description	The DQLI is 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. The absolute change of total DQLI score from before and after treatment
Time Frame	baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

One subject withdrew and three subjects were non-compliant with study procedures. Data was not analyzed for a total of four subjects.

Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Measure Participants	8
Median (Full Range) [score on a scale]	-2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Valchor Treatment of Lichen Planopilaris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.093
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Change in Follicular Units
Description	Phototrichograms of all subjects scalps performed using FotoFinder video-epiluminescence microscopy (FotoFinder Systems GmbH) in combination with TrichoScan digital image analysis (TRICHOLOG GmbH and DatInf mbH). The percent change in the total number of hairs per square cm was measured before and after treatment.
Time Frame	baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

One subject withdrew, and three subjects were non-compliant with study procedures. Data was not was not analyzed for a total of four subjects.

Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Measure Participants	8
Median (Full Range) [percent change]	-9.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Valchor Treatment of Lichen Planopilaris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.57
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Change in Mean Follicular Density
Description	Phototrichograms of all subjects scalps performed using FotoFinder video-epiluminescence microscopy (FotoFinder Systems GmbH) in combination with TrichoScan digital image analysis (TRICHOLOG GmbH and DatInf mbH). The percent change in the mean number of follicular units per square cm was measured before and after treatment.
Time Frame	baseline, 24 weeks

Outcome Measure Data

Analysis Population Description

One subject withdrew and three subjects were non-compliant with study procedures. Data was not analyzed for a total of four subjects.

Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
Measure Participants	8
Median (Full Range) [percent change]	-9.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Valchor Treatment of Lichen Planopilaris
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Time Frame	Adverse events were collect for each subject from baseline until last treatment for a total of approximately six months
Arm/Group Title	Valchor Treatment of Lichen Planopilaris
Arm/Group Description	Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris. Valchlor: Valchlor, a 0.016% gel formulation of mechlorethamine. Once daily application of Valchlor in decreasing disease activity in patients with Lichen Planopilaris.
All Cause Mortality
	Valchor Treatment of Lichen Planopilaris
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Valchor Treatment of Lichen Planopilaris
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Valchor Treatment of Lichen Planopilaris
	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)
Skin and subcutaneous tissue disorders
Contact dermatitis	11/12 (91.7%)	11
Severe Itching	1/12 (8.3%)	1

Limitations/Caveats

One subject withdrew and three subjects were non-compliant with study procedures. Data was not analyzed for a total of four subjects.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.