E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Oral Lichen Planus (OLP). OLP is a common, chronic mucosal disease associated with a cell-mediated immunological dysfunction and characterized by exacerbations of inflammation, which can lead to ulcerations of the oral mucosa associated with pain and discomfort including oral burning sensations. |
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E.1.1.1 | Medical condition in easily understood language |
OLP is a chronic condition affecting mucous membranes inside the mouth. OLP may appear as white, lacy patches; red, swollen tissues; or open sores causing burning, pain or other discomfort. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Mouth and tooth diseases [C07] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10030983 |
E.1.2 | Term | Oral lichen planus |
E.1.2 | System Organ Class | 10017947 - Gastrointestinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
1. To demonstrate the efficacy of three different doses of Rivelin®-CLO patches in treating OLP lesions over 4 weeks of treatment assessed by change in ulcer area. |
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E.2.2 | Secondary objectives of the trial |
1. To demonstrate the efficacy of 3 doses of Rivelin®-CLO patches in treating OLP lesions over 4 weeks assessed by change in lesion area. 2. To demonstrate the efficacy of 3 doses of Rivelin®-CLO patches in treating OLP lesions over 4 weeks assessed by change in 5-point erythema score. 3. To demonstrate the efficacy of 3 doses of Rivelin®-CLO patches in treating OLP lesions over 4 weeks assessed by change in Clinical global impression of anatomical site score. 4. To demonstrate the effect on patient reported daily symptoms (OLPSSM) when OLP lesions are treated by 3 doses of Rivelin®-CLO patches over 4 weeks. 5. To investigate the comfort and sensation of wearing the Rivelin®-CLO and Rivelin® plain patches after first administration and after 2 weeks of treatment. 6. To investigate the adhesion time of Rivelin®-CLO and Rivelin® plain patches applied to one OLP lesion over 4 weeks of treatment. 7. To evaluate the safety of Rivelin®-CLO patches in treating OLP lesions over 4 weeks. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. OLP patients with at least one visible and measurable symptomatic ulcerative OLP lesion , assessable via OLP Clinician Reported Outcome Measure (OLPClinROM). 2. Clinical diagnosis of symptomatic OLP supported by the Oral Lichen Planus Symptom Severity Measure (OLPSSM): The sum score of individual items #1 to #7 of the OLPSSM has to be 5 or more on at least 4 days (consecutive or not consecutive) during the last week prior to baseline/randomization visit. 3. Diagnosis of LP histologically confirmed by result of either an existing clinically relevant biopsy or a new clinically representative biopsy taken at first screening visit (i.e., a biopsy report either indicative of OLP, LP or indicative of lichenoid inflammation will be sufficient). 4. The written informed consent form has been signed and dated by the patient following receipt of verbal and written information about the study prior to carry out any study related activity. 5. Patients aged ≥ 18 years. 6. 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. 7. 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 from second screening (visit 1) to end of study (visit 7). 8. Only if a diagnostic biopsy needs to be taken at first screening visit: Complete healing of biopsy wound, including complete relief of pain associated with the biopsy site (defined as no / no further need to use any pain relief medication) at date of the second screening visit (visit 1). |
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E.4 | Principal exclusion criteria |
1. 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. 2. Ongoing active visible fungal, bacterial or viral infection of oral mucosa, including ongoing treatment of fungal or bacterial infection at second screening visit (visit 1) and/or at baseline visit. 3. Patient with any not completely healed oral surgery (including recent diagnostic biopsies, if applicable) or oral laser therapeutic wound(s) at second screening visit (visit 1). 4. 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 - Antimycotics: 4 weeks - Corticosteroids (i.v., intra-lesional, intra-articular): 4 weeks Note: intra-articular injections for the treatment of concomitant conditions (e.g. RA, activated arthrosis, acute gout, etc.) will be allowed if needed for non-OLP related disease flares during the study.
The following systemic treatments are allowed, if on stable dose for a defined period of time prior to baseline (as stated below) and throughout the study. If not on stable dose as defined, these treatments are forbidden throughout the study and have to be washed out for the periods of time prior to baseline (as stated below): - Corticosteroids (oral, rectal inhalative) washout/stable with maximum dose of 10 mg daily prednisolone or equivalent for 4 weeks - Antibiotics: washout/stable for 4 weeks - Retinoids: washout/stable for 12 weeks - Immunosuppressive drugs (e.g. azathioprine, cyclosporine, mycophenolate mofetil, hydroxychloroquine or biologics): washout/stable for 12 weeks 5. 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 6. Phototherapy in oral cavity prior to baseline visit: UVB: 2 weeks, PUVA: 4 weeks. 7. 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 the first screening visit (visit 0). 8. Known or suspected intolerance/hypersensitivity/resistance to clobetasol propionate or any component of the investigational medicinal product. 9. Note: former exclusion criterion #9 was deleted as a consequence of amendment 04. 10. Any history of oral 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. 11. History of cancer (except resected cutaneous basal cell carcinoma, except resected cutaneous squamous cell carcinoma and except resected 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. 12. Any condition or disease or circumstances that in the Investigator’s opinion would put the patient at any undue risk, prevent completion of the trial, or interfere with the analysis of the trial results. 13. Professional dental cleaning within 2 weeks prior to baseline and unwillingness to refrain from professional dental cleaning during study conduct. 14. Patients known or suspected of not being able to comply with the study protocol (e.g. due to patient’s physical or mental inability, alcoholism, drug dependency, drug abuse, psychological disorder or other conditions). 15. Close affiliation with the investigator (e.g. a close relative) or persons working at the study sites (if financially dependent on the investigator) or patient who is an employee of the Sponsor’s company. 16. 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. 17. Only if a diagnostic biopsy needs to be taken at first screening visit (visit 0): Patients with any contraindication to biopsy procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in ulcer area from baseline (visit 2) to average of visit 5 and visit 6. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the 4 weeks treatment period |
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E.5.2 | Secondary end point(s) |
1. a) Change in lesion area from baseline to average of visit 5 and visit 6 1. b) Change in 5-point erythema score from baseline to average of visit 5 and visit 6. 1. c) Change in Clinical global impression of anatomical site score from baseline to average of visit 5 and visit 6. 2. a) Change in OLPSSM total score (item #1 to #7) from baseline (run-in mean) to mean over weeks 3 and 4. 2. b) Change in individual diary symptom scores (item #1 to #7 of the OLPSSM) from baseline (run-in mean) to mean over weeks 3 and 4. 3. Change in worst symptoms at anatomical sites from baseline to average of visit 5 and visit 6. 4. The proportion of positive outcomes (score 0 or 1) on each of the 11 questions in the Patch Sensation Questionnaire assessed at day 1 and after 2 weeks of treatment. 5. The proportion of patients with successful (>=80% of days on treatment) patch applications defined as an adhesion time >=30 minutes during the 4 weeks treatment. 6. a) Frequency and intensity of adverse events (AEs) reported during the study. 6. b) Laboratory values and vital signs. 6. c) Pseudomembranous candidiasis assessed by visual inspection. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. a), b) and c): At the end of the 4 weeks treatment period. 2. a) and b): At the end of the 4 weeks treatment period 3. At the end of the 4 weeks treatment period. 4. After 2 weeks of treatment. 5. At the end of the 4 weeks treatment period. 6. a): Ongoing until end of the study. 6. b): At screening and at the end of study visit (visit 7) 6. c): At each visit until end of the study |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Denmark |
Germany |
Ireland |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |