Clinical trial NCT03656666: 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
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lichen Planus of Vulva
Female Genital Disease
Keywords: apremilast
genital erosive lichen planus
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
name: Amgen
First posted: 2018-09-04
Enrollment: 42
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double-blinded, randomized, placebo-controlled trial
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Mean GELP score at week 24 in apremilast-treated patients versus placebo-treated patients
timeFrame: 24 weeks
Secondary outcomes:
measure: Mean GELP score improvement from week 0 to week 24 in all patients
timeFrame: 24 weeks
measure: Weekly use of topical steroid, collected from patient diary
timeFrame: 24 weeks
measure: Weekly VAS pain score, collected from patient diary
timeFrame: 24 weeks
measure: Number of patients with GELP score improvement at week 16 and 24
timeFrame: 24 weeks
measure: Separate GELP score assessments: Area of involvement (in cm²)
timeFrame: 24 weeks
measure: Separate GELP score assessments: Intensity of erythema
timeFrame: 24 weeks
measure: Separate GELP score assessments: Number of erosions
timeFrame: 24 weeks
measure: Separate GELP score assessments: Striae
timeFrame: 24 weeks
measure: Separate GELP score assessments: Pressure-induced pain (VAS)
timeFrame: 24 weeks
measure: Physician Global Assessment (PGA)
timeFrame: 24 weeks
measure: Patient Global Assessment (PtGA)
timeFrame: 24 weeks
measure: DLQI score
timeFrame: 24 weeks
measure: GHQ-28 score
timeFrame: 24 weeks
measure: Sexual function assessments
timeFrame: 24 weeks
Other outcomes:
measure: Description of immune histochemical changes and expression of selected cytokines before and after apremilast therapy, assessed in vulvar or vaginal biopsies
timeFrame: 24 weeks
measure: Description of extragenital lichen planus at week 0, 16 and 24
timeFrame: 24 weeks
measure: Evaluation of clinical photos
timeFrame: 24 weeks
measure: Adverse events
timeFrame: 24 weeks
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital HF
Study officials:
affiliation: Oslo University Hospital HF
name: Anne Lise Helgesen, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: