Intra-oral Treatment of OLP With Rivelin®-CLO Patches

Sponsor

Dermtreat (Industry)

Overall Status

Completed

CT.gov ID

NCT03592342

Collaborator

Proinnovera GmbH (Industry), X-act Cologne Clinical Research GmbH (Industry)

140

Enrollment

Locations

Arms

17.7

Actual Duration (Months)

5.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Oral Lichen Planus	Drug: Clobetasol Propionate	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

140 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomization will be 1:1:1:1 to 1 of the 4 parallel arms (3 active and 1 placebo) and patients will be stratified according to number of patches needed (1-3 and 4-6).Randomization will be 1:1:1:1 to 1 of the 4 parallel arms (3 active and 1 placebo) and patients will be stratified according to number of patches needed (1-3 and 4-6).

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

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).

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 28, 2018

Actual Primary Completion Date :

Dec 20, 2019

Actual Study Completion Date :

Dec 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Rivelin® plain patches Dosing is two times per day (morning and evening) with Rivelin® plain patches (placebo).	Drug: Clobetasol Propionate Rivelin® patch is a two-layer patch comprised of a muco-adhesive, drug-delivery layer and a protective layer.
Experimental: Rivelin®-CLO patch 1µg Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 1µg Clobetasol propionate per patch.	Drug: Clobetasol Propionate Rivelin® patch is a two-layer patch comprised of a muco-adhesive, drug-delivery layer and a protective layer.
Experimental: Rivelin®-CLO patch 5µg Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 5µg Clobetasol propionate per patch.	Drug: Clobetasol Propionate Rivelin® patch is a two-layer patch comprised of a muco-adhesive, drug-delivery layer and a protective layer.
Experimental: Rivelin®-CLO patch 20µg Dosing is two times per day (morning and evening) with Rivelin®-CLO patch 20µg Clobetasol propionate per patch.	Drug: Clobetasol Propionate Rivelin® patch is a two-layer patch comprised of a muco-adhesive, drug-delivery layer and a protective layer.

Outcome Measures

Primary Outcome Measures

Change in ulcer area [4 weeks]
The change will be calculated from baseline to end of trial

Secondary Outcome Measures

Change in lesion area [4 weeks]
The change will be calculated from baseline to end of trial
Change in 5-point erythema score [4 weeks]
The change will be calculated from baseline to end of trial using a 5-point erythema score (assessed as no redness (0) or very severe redness (4))
Change in Clinical global impression score [4 weeks]
The change will be calculated from baseline to end of trial using the Clinical Global Impression Score assessed on a 5-point rating scale ranging between no disease (0) and very severe disease (4)
Change in OLPSSM total score (item #1 to #7) [4 weeks]
The change will be calculated from baseline to end of trial. The OLPSSM (OLP Symptom Severity Measure) is a recently developed questionnaire, which serves for the patient to assess his/her specific OLP symptoms. This questionnaire consists of overall 12 items, to be assessed at different time points. Most items should be completed on a daily basis (in the evening). These items will be assessed as part of the patient's eDiary
Change in individual diary symptom scores (item #1 to #7 of the OLPSSM) [4 weeks]
The change will be calculated from baseline to end of trial. The OLPSSM (OLP Symptom Severity Measure) is a recently developed questionnaire, which serves for the patient to assess his/her specific OLP symptoms. This questionnaire consists of overall 12 items, to be assessed at different time points. Most items should be completed on a daily basis (in the evening). These items will be assessed as part of the patient's eDiary.
Change in worst symptoms at anatomical sites [4 weeks]
The change will be calculated from baseline to end of trial
The proportion of positive outcomes (score 0 or 1) on each of the 11 questions in the Patch Sensation Questionnaire [2 weeks]
The patient will assess the sensation of wearing the Rivelin® patches by answering 11 questions (the Patch sensation questionnaire) according to 5-point rating scales (ranging between 0 [most positive response] and 4 [most negative response]).The Patch Sensation Questionnaire will be completed during the clinic visit at baseline (visit 2) after first patch application and at visit 4 (2 weeks).
The proportion of patients with successful (>=80% of days on treatment) patch applications [4 weeks]
Defined as an adhesion time more than 30 minutes during the 4 weeks treatment
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) [4 weeks]
Frequency and intensity of adverse events (AEs) reported during the study

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	QWay Research	Hialeah	Florida	United States	33010
2	Vitae Research Center, LLC	Miami	Florida	United States	33135
3	Valencia Medical & Research Center	Miami	Florida	United States	33165
4	The Dental College of Georgia	Augusta	Georgia	United States	30912
5	Tufts University, School of Dental Medicine	Boston	Massachusetts	United States	02111
6	Brigham and Women's Hospital, Division of Oral Medicine and Dentistry	Boston	Massachusetts	United States	02115
7	NYU College of Dentistry, Bluestone Center for Clinical Research	New York	New York	United States	10010
8	UNC Dermatology and Skin Cancer Center	Chapel Hill	North Carolina	United States	27516
9	Carolinas Center for Oral Health	Charlotte	North Carolina	United States	28209
10	University of Pennsylvania Health System, Dept. Oral amd Maxillofacial Surgery	Philadelphia	Pennsylvania	United States	19104
11	Texas A&M University (TAMU), College of Dentistry	Dallas	Texas	United States	75246
12	UT Southwestern Medical Center Department of Surgery	Dallas	Texas	United States	75390-9109
13	ENT Associates of Texas	Frisco	Texas	United States	75035
14	The Oral and Facial Surgery Center	Clearfield	Utah	United States	84105
15	Kaye Edmonton Clinic	Edmonton	Alberta	Canada	T6G1Z1
16	Health Sciences North, North East Cancer Center	Sudbury	Ontario	Canada	P3E5JL
17	Rigshospitalet	Copenhagen		Denmark	2100
18	University of Copenhagen Department of Odontology	Copenhagen		Denmark	2100
19	LMU München, Klinik und Poliklinik für Dermatologie und Allergologie	Munich		Germany	80337
20	Cork University Dental School and Hospital	Cork		Ireland	T12 E8YV
21	School of Dental Sciences Newcastel Upon Tyne	Newcastle Upon Tyne	Newcastel	United Kingdom	NE2 4BW
22	Edinburgh Dental Institute	Edinburgh		United Kingdom	EH3 9HA
23	University of Glasgow Dental School	Glasgow		United Kingdom	G2 3JZ
24	Leeds Dental Institute	Leeds		United Kingdom	LS9 9LU
25	King´s College London Dental Institute, Oral Clinical Research Unit	London		United Kingdom	SE1 9RT
26	University College London and University College London Hospitals Trust	London		United Kingdom	WC1X 8LD
27	University of Sheffield, School of Clinical Dentistry	Sheffield		United Kingdom	S10 2TA