Oral Lichen Planus
Conditions
Brief summary
Apremilast for the management of oral lichen planus.
Detailed description
Oral lichen planus (OLP) affects approximately 1.27% of the general population. Inflammatory responses constitute a major component of OLP pathogenesis where targeted therapies play an important role in managing this condition. Apremilast is a new well-tolerated and relatively safe anti-inflammatory therapy that has been approved for managing psoriasis and psoriatic arthritis. Given its safer profile, Apremilast may ameliorate inflammatory responses in clinically active OLP without the experience of serious adverse events associated with other systemic immunosuppressive therapies used to treat OLP. The plan is to conduct a single-center, explanatory, randomized, 16 weeks, parallel group, superiority, blinded, placebo-controlled, clinical trial. The main objective is treatment success assessment. Other objectives include exploring the efficacy of Apremilast in clinically active OLP adult patients considered for systemic treatment and failed topical corticosteroid therapy. It is hypothesized that Apremilast will induce more treatment success as compared to placebo in patients who failed the standard treatment of topical corticosteroids.
Interventions
DRUGApremilast
Apremilast tablets. Titration will occur in the initial five days of treatment as per dosing in psoriasis as follows: Day 1: 10 mg; Day 2: 20 mg; Day 3: 30 mg; Day 4: 40 mg; Day 5: 50 mg. Day 6 and thereafter patients will be dosed at 60 mg for a total of 12 weeks.
DRUGPlacebo
Placebo Oral tablets. Patients randomized to the control arm will receive color, taste, shape and odour matched oral placebo. The number of tablets and the days taken is analogous to the intervention arm had they been randomized to the intervention arm.
Sponsors
Celgene
Sunnybrook Research Institute
Sunnybrook Health Sciences Centre
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Each participant must meet all of the following inclusion criteria to participate in this study: 1. Must be 18 years or older at time of consent. 2. Patients must have clinically active OLP that is being considered for systemic therapy; and an oral biopsy within the last 12 months of randomization showing a lichenoid reaction correlating clinically with OLP. 3. Must have failed topical corticosteroids therapy. Topical corticosteroid failure is defined as receiving a trial of at least 4 weeks of high potency topical corticosteroids without achieving sufficient improvement by patients. 4. Must be in general good health (except for disease under study) as judged by the Investigator, based on medical history, physical examination, clinical laboratories, and urinalysis. (NOTE: The definition of good health means a subject does not have uncontrolled significant co-morbid conditions). Laboratory work-up includes the following: complete blood count (CBC), creatinine, albumin, aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total bilirubin, serum, Beta-HCG (if female), Hepatitis C antibodies and HgbA1C. 5. Male participants must use a recognized effective method of contraception with any female partner (i.e. at a minimum, barrier plus an additional method of contraception) while on investigational product and for at least 4 weeks after taking the last dose of investigational product. 6. Female participants of childbearing potential (FCBP)† must have a negative pregnancy test at Screening. While on investigational product and for at least 4 weeks after taking the last dose of investigational product, FCBP who engage in activity in which conception is possible must use one of the approved contraceptive§ options described below: 1. Option 1: Any one of the following highly effective methods: hormonal contraception (oral, injection, implant, transdermal patch, vaginal ring); intrauterine device (IUD); tubal ligation; prior hysterectomy; prior bilateral oophorectomy or salpingo-oophorectomy; or partner's vasectomy; OR 2. Option 2: Male or female condom (latex condom or nonlatex condom NOT made out of natural \[animal\] membrane \[for example, polyurethane\]; plus one additional barrier method: (a) diaphragm with spermicide; (b) cervical cap with spermicide; or (c) contraceptive sponge with spermicide. * A female of childbearing potential is a sexually mature female who 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been postmenopausal for at least 24 consecutive months (that is, has had menses at any time during the preceding 24 consecutive months). * The female subject's chosen form of contraception must be effective by the time the female subject is randomized into the study (for example, hormonal contraception should be initiated at least 28 days before randomization).
Exclusion criteria
All participants meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessing treatment success defined as Physician Global Assessment (PhGA) of 0 or 1 | Baseline to 16 weeks | The primary outcome will be assessing treatment success with Apremilast as compared to placebo defined as Physician Global Assessment (PhGA) of 0 or 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Physician Global Assessment (PhGA) | Baseline to 16 weeks | Physician Global Assessment (PhGA) grading score from 0 to 4. Score of 0 is clear, score of 1 is almost clear, score of 2 is mild disease, score of 3 is moderate disease, and a score of 4 is severe disease. |
| Patient Assessment (PtA) | Baseline to 16 weeks | Patient Assessment (PtA) grading score from 0 to 4. Score of 0 is clear, score of 1 is almost clear, score of 2 is mild disease, score of 3 is moderate disease, and a score of 4 is severe disease. |
| Achieving partial response | Baseline to 12 weeks | Percentage of patients who achieve partial response |
| Visual Analogue Scale (VAS) | Baseline to 16 weeks | Patient assessment of pain score from 0 to 10. VAS is a scale demonstrated by a 10 cm horizontal line marked from 0-10 with the left end marked as no symptoms (0) and the right end marked as worst symptoms (10). |
| Achieving complete remission defined as achieving a score of 0 on PhGA scale | 12 weeks and 16 weeks | Complete remission is defined as achieving a score of 0 on PhGA scale |
| Modified Oral Mucositis Index (MOMI) Scale | Baseline weeks to 16 weeks | Physician assessment using a validated 20 item scale in OLP, is used to rate four types of mucosal changes (atrophy, edema, erythema, and ulceration) in nine anatomical areas of the oral cavity |
| Safety and tolerability of Apremilast | 6 weeks to 16 weeks | Relationship of adverse events to study treatment. Difference in proportions between the two study arms for each AE at each time point will be assessed and changes in the incidence of treatment. |
| Standardized steroid and anti-fungal rinses used | 6 weeks to 16 weeks | Differences in total dexamethasone and nystatin mouthwashes quantity used at each time point between the two study arms will be assessed |
| Body Mass Index (BMI) | Baseline to 16 weeks | Differences in BMI scores at each time point between two study arms will be assessed |
| Oral Health Impact Profile (OHIP-14) Scale | Baseline to 16 weeks | Patient assessment of overall disease impact on quality of life is a self-filled validated scale that focuses on seven domains: functional limitation, physical pain, psychological discomfort, physical disability, psychological disability, social disability and handicap. Participants will be asked to respond according to frequency of impact on a 5-point scale coded: never (score 0), hardly ever (score 1), occasionally (score 2), fairly often (score 3) and very often (score 4). |
Countries
Canada
Outcome results
None listed