Intra-oral Treatment of OLP With Rivelin®-CLO Patches
A Randomized, Double-blind, Placebo-controlled, Parallel Group Clinical Study to Assess the Safety and Efficacy of Three Doses of Clobetasol Propionate When Administered Intra-orally Twice Daily in Patients With Oral Lichen Planus (OLP) Using Rivelin®-CLO Patches
Participants with symptomatic Oral Lichen Planus lesions will be treated with Rivelin® patches containing either 0, 1, 5, or 20 μg clobetasol per patch. Each participant will apply up to 6 patches twice daily for 4 weeks.
Randomized, double-blind, placebo-controlled, parallel group clinical study with 3 active dose arms (Rivelin®-CLO patches) and one placebo arm (Rivelin® plain patch). Up to 6 Rivelin® patches will be applied to symptomatic ulcerative and symptomatic erythematous OLP lesions.
After screening (visit 1, day -14 to day -7), patients who have signed the informed consent form and who are fulfilling the inclusion criteria and none of the exclusion criteria will be randomized at baseline (visit 2, day 1) to one of the four treatment arms in a double-blinded fashion.
Arm A: Rivelin® plain patch (Placebo)
Arm B: Rivelin®-CLO 1 μg/patch
Arm C: Rivelin®-CLO 5 μg/patch
Arm D: Rivelin®-CLO 20 μg/patch Randomization will be 1:1:1:1 and patients will be stratified according to number of patches needed (1-3 and 4-6).
The screening phase ranges between 7 and 14 days, i.e. that the screening visit (visit 1) needs to be performed 7 days prior to baseline at latest. For visits 3 (day 8), 4 (day 15), 5 (day 22), and 6 (day 29) a visit window of +/- 2 days will be allowed. Visit 7 will be defined as visit 6 + 14 days, with a visit window of +/- 3 days.
Randomized patients will enter a 28-days (4-weeks) treatment period. Dosing is two times per day (morning and evening) with patches applied directly on OLP lesions as instructed by a clinician or delegated site staff. Patients will record symptoms and adhesion time in daily diaries by using an electronic diary (eDiary).
During the treatment period, the treating physician or dentist will perform an assessment of the disease status on a weekly basis. A final examination of disease status will be performed at the follow-up visit (visit 7), 14 days after the end of treatment.
Other treatments of symptomatic OLP lesions during the study are prohibited. Only rescue analgesics determined by the investigator at study entry on a patient specific basis are allowed to be taken, in case that OLP associated symptoms like pain cannot be managed by the sole use of the patches. All doses of rescue analgesics will be recorded by the patient in the eDiary.
If the patients' condition is worsening (at the discretion of the investigator) and if associated symptoms cannot longer be managed acceptably by the additional use of rescue analgesics, i.e. if there is the need to start any other OLP treatment, IMP treatment for that patient should be discontinued prematurely and patient should be withdrawn from the study.
At visit 3 (day 8), a blood sample will be drawn to measure the blood plasma concentration of clobetasol and to determine the morning serum cortisol level (between 7 and 9 AM).
All patients will have a follow-up visit that will be performed 2 weeks after the EoT/ET visit (visit 6).
Safety data (by means of AE documentation including fungal infections and SAE reporting) will be closely monitored by an independent Data and Safety Monitoring Board (DSMB). DSMB will advise the Sponsor of any potential risk for the safeguard of patients.
Dosing is two times per day (morning and evening) with Rivelin® plain patches (placebo).
Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 1µg Clobetasol propionate per patch.
Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 5µg Clobetasol propionate per patch.
Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 20µg Clobetasol propionate per patch.
Inclusion Criteria: OLP patients with at least one visible and measurable symptomatic ulcerative OLP lesion, assessable via OLP Clinician Reported Outcome Measure (OLPClinROM). Diagnosis of LP histologically confirmed by result of either an existing clinically relevant biopsi or a new clinically representative biopsy at first screening visit (i.e. a biopsy report either indicative of OLP, LP or indicative of lichenoid inflammation will be sufficient). Patients aged ≥ 18 years. Patients practicing daily oral hygiene (by tooth brushing and/or mouth rinse) and willing to maintain at least their routine oral hygiene procedure during study participation. Willingness to keep already used permitted concomitant medication, food supplements (e.g. probiotics) or herbals, which might have in the discretion of the investigator a potential influence on OLP, on a stable basis during the study. Exclusion Criteria: Patients requiring more than 6 patches (corresponding to an area of approximately 3 cm2 per patch) to cover symptomatic ulcerative and erythematous OLP lesions at baseline visit. Ongoing active visible fungal, bacterial or viral infection of oral mucosa, including ongoing treatment of those at baseline. Patient with any un-healed oral surgery (including recent diagnostic biopsies, if applicable) or oral laser therapeutic wound(s) at baseline visit. Any of the following systemic treatments prior to baseline visit and throughout the study: Protease inhibitors used for the treatment of HIV (e.g. atazanavir, idinavir, nelfinavir, etc.): 1 week Corticosteroids (i.v., intra articular, intra-lesional): 4 weeks Antimycotics: 4 weeks The following systemic treatments are allowed, if on stable dose for a defined period of time to baseline and throughout the study. Antibiotics: 4 weeks Corticosteroids (oral, rectal, inhalative) washout/stable with maxinum dose of 10 mg daily prednisolone or equivalent for 4 weeks. Retinoids: 12 weeks Immunosuppressive drugs (e.g. azathioprine, cyclosporine, mycophenolate mofetil, or biologics): 12 weeks Any of the following topical treatments used in the oral cavity prior to baseline visit: Corticosteroids: 2 weeks Antibiotics: 2 weeks Cyclosporine: 2 weeks Tacrolimus, pimecrolimus: 2 weeks Antimycotics: 2 weeks Retinoids: 4 weeks Phototherapy in oral cavity prior to baseline visit: UVB, PUVA. Current participation in another clinical study and/or having received treatment with any non-marketed / investigational medicinal product (drug substance or medical device) within 4 weeks prior to screening. Known or suspected intolerance/hypersensitivity/resistance to clobetasol propionate or any component of the investigational medicinal product. Any history of squamous cell carcinoma (even if resected), as well as history of other non-squamous cell carcinoma (e.g. sarcoma, salivary gland tumors) that have been managed with radiation or chemotherapy. History of cancer (except resected cutaneous basal cell carcinoma and except in situ cervical cancer) unless it can be documented that the patient has been in a disease-free state for at least 5 years, or at least 2 years in a disease-free state for low-grade cancers. In case of clinical suspicion of malignancy in the oral cavity, a patient can only be included after an excluding biopsy. Professional dental cleaning within 2 weeks prior to baseline and unwillingness to refrain from professional dental cleaning during study conduct. Close affiliation with the investigator (e.g. a close relative) or persons working at the study sites or patient who is an employee of the Sponsor's company. Pregnant, confirmed by a positive pregnancy test, or nursing (lactating) women, or women of childbearing potential (WOCP) planning to become pregnant or WOCP not using or willing to continue to use a defined highly effective method of contraception throughout the study.