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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 140
- 试验地点
- 27
- 主要终点
- Change in ulcer area
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
All 4 interventions will be similar in appearance and be allocated by use of a blinded kit number (each kit contains drug for 1 week).
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Rivelin® plain patches
Dosing is two times per day (morning and evening) with Rivelin® plain patches (placebo).
干预措施: Clobetasol Propionate (Drug)
Rivelin®-CLO patch 1µg
Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 1µg Clobetasol propionate per patch.
干预措施: Clobetasol Propionate (Drug)
Rivelin®-CLO patch 5µg
Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 5µg Clobetasol propionate per patch.
干预措施: Clobetasol Propionate (Drug)
Rivelin®-CLO patch 20µg
Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 20µg Clobetasol propionate per patch.
干预措施: Clobetasol Propionate (Drug)
结局指标
主要结局
Change in ulcer area
时间窗: 4 weeks
The change will be calculated from baseline to end of trial
次要结局
- Change in lesion area(4 weeks)
- Change in 5-point erythema score(4 weeks)
- Change in Clinical global impression score(4 weeks)
- Change in OLPSSM total score (item #1 to #7)(4 weeks)
- Change in individual diary symptom scores (item #1 to #7 of the OLPSSM)(4 weeks)
- Change in worst symptoms at anatomical sites(4 weeks)
- The proportion of positive outcomes (score 0 or 1) on each of the 11 questions in the Patch Sensation Questionnaire(2 weeks)
- The proportion of patients with successful (>=80% of days on treatment) patch applications(4 weeks)
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)(4 weeks)