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The AP-GELP Study: A Clinical Trial on the Effects of Apremilast in Female Genital Erosive Lichen Planus

Primary Purpose

Lichen Planus of Vulva, Female Genital Disease

Status
Active
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Apremilast
Placebo
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lichen Planus of Vulva focused on measuring apremilast, genital erosive lichen planus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Moderate to severe GELP at inclusion with the diagnosis based on characteristic clinical and/or histological features. Minimum GELP score 5/30 in vagina and/or vulva (scored separately), of which erythema and pain ≥1 are mandatory
  • Informed consent from the patient to the protocol and clinical procedures.

Exclusion Criteria:

  • Patients receiving other systemic immune modulating therapy
  • Concomitant use of strong CYP3A4 enzyme inducers
  • Inadequate birth control, pregnancy and/or breast-feeding
  • Depression and suicidal ideation
  • Patients with severe renal impairment
  • Patients with active tuberculosis, serious infections or cancer
  • Unexplained and clinically significant weight loss in underweight patients
  • Hypersensitivity to the active substance(s) or to any of the excipients
  • Hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption
  • Participating in another trial that might affect the current study or there should be minimum 90 days between participation in another intervention trial

Sites / Locations

  • Oslo University Hospital HF

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Apremilast

Placebo + Apremilast

Arm Description

Week 0-24: 21 patients will receive apremilast oral tablets with initial standard titration of dose day 1-6 followed by standard dose of 30 mg apremilast b.i.d. Initial titration: Day 1: 10 mg in morning. Day 2: 10 mg in morning and 10 mg in evening. Day 3: 10 mg in morning and 20 mg in evening. Day 4: 20 mg in morning and 20 mg in evening. Day 5: 20 mg in morning and 30 mg in evening. Day 6 and thereafter: 30 mg twice daily.

Week 0-24: 21 patients will receive matching placebo oral tablets, with initial titration.

Outcomes

Primary Outcome Measures

Mean GELP score at week 24 in apremilast-treated patients versus placebo-treated patients
The GELP (Genital Erosive Lichen Planus) score is a scoring system for clinical assessment of genital erosive lichen planus (GELP) in women. Area of genital involvement, erythema, striae, number of erosions and pain are registered and scored 0-3 (0 is none) for each parameter. Vulval and vaginal involvement is assessed separately, resulting in a maximum GELP score of 30.

Secondary Outcome Measures

Mean GELP score improvement from week 0 to week 24 in all patients
The GELP (Genital Erosive Lichen Planus) score is a scoring system for clinical assessment of genital erosive lichen planus (GELP) in women. Area of genital involvement, erythema, striae, number of erosions and pain are registered and scored 0-3 (0 is none) for each parameter. Vulval and vaginal involvement is assessed separately, resulting in a maximum GELP score of 30.
Weekly use of topical steroid, collected from patient diary
Frequency of application is recorded once a week in the patient diary as the number of days being used per week
Weekly VAS pain score, collected from patient diary
VAS is recorded once a week in the patient diary using a visual linear scale of 100mm ranging from 0 (no pain) to 10 (worst imaginable pain).
Number of patients with GELP score improvement at week 16 and 24
The GELP (Genital Erosive Lichen Planus) score is a scoring system for clinical assessment of genital erosive lichen planus (GELP) in women. Area of genital involvement, erythema, striae, number of erosions and pain are registered and scored 0-3 (0 is none) for each parameter. Vulval and vaginal involvement is assessed separately, resulting in a maximum GELP score of 30.
Separate GELP score assessments: Area of involvement (in cm²)
Range 0-3 (none=0, <3 cm²=1, 3-6 cm²=2, >6 cm²=3). Recorded as part of the GELP score at time points specified in the protocol.
Separate GELP score assessments: Intensity of erythema
Range 0-3 (none=0, mild=1, moderate=2, strong=3). Recorded as part of the GELP score at time points specified in the protocol.
Separate GELP score assessments: Number of erosions
Range 0-3 (none=0, 1=1, 2-3=2, >3=3). Recorded as part of the GELP score at time points specified in the protocol.
Separate GELP score assessments: Striae
Range 0-3 (none=0, minimal=1, moderate=2, extensive=3). Recorded as part of the GELP score at time points specified in the protocol.
Separate GELP score assessments: Pressure-induced pain (VAS)
Patient-reported pain is induced by pressuring the involved area with a cotton swab, using a visual linear scale of 100mm ranging from 0 (no pain) to 10 (worst imaginable pain). GELP score range 0-3 (no pain=0, VAS 1-3=1, VAS 4-6=2,VAS 7-10=3). Recorded as part of the GELP score at time points specified in the protocol.
Physician Global Assessment (PGA)
5-point disease severity scoring system, assessed by the clinician at time points specified in the protocol (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
Patient Global Assessment (PtGA)
5-point disease severity scoring system, assessed by the patient at time points specified in the protocol (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
DLQI score
The Dermatology Life Quality Index (DLQI) is a 10-question validated questionnaire. Each question is scored 0-3, with a maximum score of 30. The higher the score, the more quality of life is impaired. The time points for DLQI score are specified in the protocol.
GHQ-28 score
GHQ-28 is a 28-item version of the General Health Questionnaire (GHQ) subdivided into somatic symptoms, anxiety/insomnia, social dysfunction and severe depression. Each question is scored 0-1. The higher the score, the more severe the condition.The time points for GHQ-28 score are specified in the protocol.
Sexual function assessments
The Female Sexual Distress Scale - Revised (FSDS-R) is a 13-item questionnaire used for sexual function assessment. Each question is scored 0-4. The total score range is 0-52, with higher scores indicating more sexually related distress.

Full Information

First Posted
August 15, 2018
Last Updated
March 28, 2023
Sponsor
Oslo University Hospital
Collaborators
Celgene Corporation, Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT03656666
Brief Title
The AP-GELP Study: A Clinical Trial on the Effects of Apremilast in Female Genital Erosive Lichen Planus
Official Title
The AP-GELP Study: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Phosphodiesterase 4-Inhibitor Apremilast in Female Genital Erosive Lichen Planus
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 24, 2019 (Actual)
Primary Completion Date
November 30, 2022 (Actual)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
Celgene Corporation, Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
Genital erosive lichen planus (GELP) is a chronic inflammatory disease causing painful genital sores and scarring in women. Treatment options are limited and often unsatisfactory. This trial will study the effects of treatment with apremilast and quality of life and sexual function in women with GELP.
Detailed Description
Genital erosive lichen planus (GELP) is a chronic, inflammatory and scarring genital disease. The disease may have a significant impact on daily living, quality of life and sexual function. There is a considerable lack of high-quality evidence on treatment options for GELP and few effective therapeutic facilities available in current clinical practice. The aims of this study are to investigate clinical and immunohistochemical effects of a new oral anti-inflammatory treatment, apremilast, for women with moderate-to-severe GELP in a double-blinded, randomized, placebo-controlled trial (RCT). Apremilast is an inhibitor of phosphodiesterase 4 (PDE4) with documented effect in several inflammatory skin diseases, but it has not yet been studied in patients with GELP. The drug dose and study design have been chosen based on relevant experience from other studies on apremilast, and is equivalent to the dose used for approved indications (chronic plaque psoriasis and psoriatic arthritis). The main objective of this trial is to assess the efficacy of apremilast in the treatment of GELP in women. Secondary objectives include Description of immunohistochemical changes in lichen planus lesions Assessment of safety of apremilast in the treatment of GELP Assessment of quality of life and sexual function

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lichen Planus of Vulva, Female Genital Disease
Keywords
apremilast, genital erosive lichen planus

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
Double-blinded, randomized, placebo-controlled trial
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Apremilast
Arm Type
Active Comparator
Arm Description
Week 0-24: 21 patients will receive apremilast oral tablets with initial standard titration of dose day 1-6 followed by standard dose of 30 mg apremilast b.i.d. Initial titration: Day 1: 10 mg in morning. Day 2: 10 mg in morning and 10 mg in evening. Day 3: 10 mg in morning and 20 mg in evening. Day 4: 20 mg in morning and 20 mg in evening. Day 5: 20 mg in morning and 30 mg in evening. Day 6 and thereafter: 30 mg twice daily.
Arm Title
Placebo + Apremilast
Arm Type
Placebo Comparator
Arm Description
Week 0-24: 21 patients will receive matching placebo oral tablets, with initial titration.
Intervention Type
Drug
Intervention Name(s)
Apremilast
Other Intervention Name(s)
Otezla
Intervention Description
Apremilast oral tablets
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo (for apremilast)
Intervention Description
Placebo oral tablets
Primary Outcome Measure Information:
Title
Mean GELP score at week 24 in apremilast-treated patients versus placebo-treated patients
Description
The GELP (Genital Erosive Lichen Planus) score is a scoring system for clinical assessment of genital erosive lichen planus (GELP) in women. Area of genital involvement, erythema, striae, number of erosions and pain are registered and scored 0-3 (0 is none) for each parameter. Vulval and vaginal involvement is assessed separately, resulting in a maximum GELP score of 30.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Mean GELP score improvement from week 0 to week 24 in all patients
Description
The GELP (Genital Erosive Lichen Planus) score is a scoring system for clinical assessment of genital erosive lichen planus (GELP) in women. Area of genital involvement, erythema, striae, number of erosions and pain are registered and scored 0-3 (0 is none) for each parameter. Vulval and vaginal involvement is assessed separately, resulting in a maximum GELP score of 30.
Time Frame
24 weeks
Title
Weekly use of topical steroid, collected from patient diary
Description
Frequency of application is recorded once a week in the patient diary as the number of days being used per week
Time Frame
24 weeks
Title
Weekly VAS pain score, collected from patient diary
Description
VAS is recorded once a week in the patient diary using a visual linear scale of 100mm ranging from 0 (no pain) to 10 (worst imaginable pain).
Time Frame
24 weeks
Title
Number of patients with GELP score improvement at week 16 and 24
Description
The GELP (Genital Erosive Lichen Planus) score is a scoring system for clinical assessment of genital erosive lichen planus (GELP) in women. Area of genital involvement, erythema, striae, number of erosions and pain are registered and scored 0-3 (0 is none) for each parameter. Vulval and vaginal involvement is assessed separately, resulting in a maximum GELP score of 30.
Time Frame
24 weeks
Title
Separate GELP score assessments: Area of involvement (in cm²)
Description
Range 0-3 (none=0, <3 cm²=1, 3-6 cm²=2, >6 cm²=3). Recorded as part of the GELP score at time points specified in the protocol.
Time Frame
24 weeks
Title
Separate GELP score assessments: Intensity of erythema
Description
Range 0-3 (none=0, mild=1, moderate=2, strong=3). Recorded as part of the GELP score at time points specified in the protocol.
Time Frame
24 weeks
Title
Separate GELP score assessments: Number of erosions
Description
Range 0-3 (none=0, 1=1, 2-3=2, >3=3). Recorded as part of the GELP score at time points specified in the protocol.
Time Frame
24 weeks
Title
Separate GELP score assessments: Striae
Description
Range 0-3 (none=0, minimal=1, moderate=2, extensive=3). Recorded as part of the GELP score at time points specified in the protocol.
Time Frame
24 weeks
Title
Separate GELP score assessments: Pressure-induced pain (VAS)
Description
Patient-reported pain is induced by pressuring the involved area with a cotton swab, using a visual linear scale of 100mm ranging from 0 (no pain) to 10 (worst imaginable pain). GELP score range 0-3 (no pain=0, VAS 1-3=1, VAS 4-6=2,VAS 7-10=3). Recorded as part of the GELP score at time points specified in the protocol.
Time Frame
24 weeks
Title
Physician Global Assessment (PGA)
Description
5-point disease severity scoring system, assessed by the clinician at time points specified in the protocol (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
Time Frame
24 weeks
Title
Patient Global Assessment (PtGA)
Description
5-point disease severity scoring system, assessed by the patient at time points specified in the protocol (0=clear, 1=almost clear, 2=mild, 3=moderate, 4=severe).
Time Frame
24 weeks
Title
DLQI score
Description
The Dermatology Life Quality Index (DLQI) is a 10-question validated questionnaire. Each question is scored 0-3, with a maximum score of 30. The higher the score, the more quality of life is impaired. The time points for DLQI score are specified in the protocol.
Time Frame
24 weeks
Title
GHQ-28 score
Description
GHQ-28 is a 28-item version of the General Health Questionnaire (GHQ) subdivided into somatic symptoms, anxiety/insomnia, social dysfunction and severe depression. Each question is scored 0-1. The higher the score, the more severe the condition.The time points for GHQ-28 score are specified in the protocol.
Time Frame
24 weeks
Title
Sexual function assessments
Description
The Female Sexual Distress Scale - Revised (FSDS-R) is a 13-item questionnaire used for sexual function assessment. Each question is scored 0-4. The total score range is 0-52, with higher scores indicating more sexually related distress.
Time Frame
24 weeks
Other Pre-specified Outcome Measures:
Title
Description of immune histochemical changes and expression of selected cytokines before and after apremilast therapy, assessed in vulvar or vaginal biopsies
Description
Asessment in biopsies at week 0 and 24
Time Frame
24 weeks
Title
Description of extragenital lichen planus at week 0, 16 and 24
Description
Extragenital lichen planes is described and compared at 0,16 and 24 weeks
Time Frame
24 weeks
Title
Evaluation of clinical photos
Description
Clinical photos of lichen planus lesions are taken by a medical photographer at week 0 and 24
Time Frame
24 weeks
Title
Adverse events
Description
Adverse events are registered at time point described in the protocol
Time Frame
24 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Moderate to severe GELP at inclusion with the diagnosis based on characteristic clinical and/or histological features. Minimum GELP score 5/30 in vagina and/or vulva (scored separately), of which erythema and pain ≥1 are mandatory Informed consent from the patient to the protocol and clinical procedures. Exclusion Criteria: Patients receiving other systemic immune modulating therapy Concomitant use of strong CYP3A4 enzyme inducers Inadequate birth control, pregnancy and/or breast-feeding Depression and suicidal ideation Patients with severe renal impairment Patients with active tuberculosis, serious infections or cancer Unexplained and clinically significant weight loss in underweight patients Hypersensitivity to the active substance(s) or to any of the excipients Hereditary problems of galactose intolerance, lactase deficiency or glucose-galactose malabsorption Participating in another trial that might affect the current study or there should be minimum 90 days between participation in another intervention trial
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anne Lise Helgesen, MD PhD
Organizational Affiliation
Oslo University Hospital HF
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hospital HF
City
Oslo
ZIP/Postal Code
0424
Country
Norway

12. IPD Sharing Statement

Learn more about this trial

The AP-GELP Study: A Clinical Trial on the Effects of Apremilast in Female Genital Erosive Lichen Planus

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