The AP-GELP Study: A Randomized, Placebo-Controlled Clinical Trial on the Effects of Phosphodiesterase 4-Inhibitor Apremilast in Female Genital Erosive Lichen Planus
Trial Snapshot
- Phase
- Phase 2
- Status
- Active, not recruiting
- Sponsor
- Enrollment
- 42
- Locations
- 1
- Primary Endpoint
- Mean GELP score at week 24 in apremilast-treated patients versus placebo-treated patients
Study Overview
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
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Apremilast
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.
Intervention: Apremilast (Drug)
Placebo + Apremilast
Week 0-24: 21 patients will receive matching placebo oral tablets, with initial titration.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Mean GELP score at week 24 in apremilast-treated patients versus placebo-treated patients
Time Frame: 24 weeks
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 Outcomes
- Weekly use of topical steroid, collected from patient diary(24 weeks)
- Number of patients with GELP score improvement at week 16 and 24(24 weeks)
- Separate GELP score assessments: Striae(24 weeks)
- Separate GELP score assessments: Pressure-induced pain (VAS)(24 weeks)
- Physician Global Assessment (PGA)(24 weeks)
- Patient Global Assessment (PtGA)(24 weeks)
- Separate GELP score assessments: Area of involvement (in cm²)(24 weeks)
- DLQI score(24 weeks)
- Mean GELP score improvement from week 0 to week 24 in all patients(24 weeks)
- Separate GELP score assessments: Number of erosions(24 weeks)
- Weekly VAS pain score, collected from patient diary(24 weeks)
- Separate GELP score assessments: Intensity of erythema(24 weeks)
- GHQ-28 score(24 weeks)
- Sexual function assessments(24 weeks)
Investigators
Anne Lise Helgesen
Principal Investigator
Oslo University Hospital