search
Back to results

Lichen Planus Mucosae at USZ, Efficacy of Oral Alitretinoin

Primary Purpose

Lichen Planus (LP)

Status
Unknown status
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
alitretinoin
Sponsored by
University of Zurich
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lichen Planus (LP)

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  • Aged 18 to 75 years
  • MLP for at least 3 months
  • Disease activity according to Escudier score of 10 points or greater or erosive lesion of any score
  • Refractory to standard topical therapy
  • Consensus to a 2 weeks wash-out period of topical steroids before starting study treatment

Exclusion criteria

  • Unable to comply with the requirements of the study
  • Pregnant or lactating women
  • Female patients of childbearing potential who cannot use or will not commit to using two effective forms of contraception simultaneously under supervision of the investigator or a gynecologist
  • Active hepatitis and/or vaccination against hepatitis A/B during the last 4 weeks
  • Adequate control of the disease by standard topical therapy and standard topical corticosteroid therapy
  • Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component

  • Patients treated with any of the following treatments 4 weeks before the start of study treatment:

    1. systemic drugs: corticosteroids, immunosuppressants, methotrexate
    2. phototherapy
  • Treatment with any systemic or topical retinoids within 1 year or 1 month, respectively, before start of study treatment or treatment with systemic retinoids for treatment for MLP at any time

  • coexistence of any serious medical condition which, in the opinion of the investigator, may interfere with the safety of the patient, including

    1. hepatic insufficiency (alanine aminotransferase and /or aspartate aminotransferase values > 2.5 x ULN)
    2. severe renal failure
    3. uncontrolled hypertriglyceridemia (triglycerides >150 % of the upper limit of normal),
    4. uncontrolled hypercholesterolemia (cholesterol or low density lipoprotein (LDL) cholesterol values > 1.5 x ULN
    5. Patients with cardiovascular risk factors that would exclude a starting dose of 30 mg of alitretinoin
    6. Uncontrolled hypothyroidism
    7. Hypervitaminosis A
    8. Active major psychiatric disorder including depression and suicidal ideation
  • Concomitant medications such as systemic tetracyclines, CYP3A4 inhibitors such as ketoconazole, Vitamin A or St. John's Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before start of study treatment
  • Trial participation within 2 months before start of study treatment (3 months for biologics)

Sites / Locations

  • University Hospital Zurich, Division of DermatologyRecruiting

Outcomes

Primary Outcome Measures

Efficacy of alitretinoin (Toctino®) based on the Escudier score of oral lesions at baseline and after 24 weeks of treatment.
The primary objective is to determine the efficacy of alitretinoin (Toctino®) in reducing signs and symptoms of severe mucosal lichen planus with respect to the proportion of responders based on the, Escudier score of oral lesions at baseline and after 24 weeks of treatment or at the latest assessment for patients who withdrew prematurely (Last Observation Carried Forward, LOCF). Response is defined as a 50 % reduction in the total Escudier score compared to the baseline values.

Secondary Outcome Measures

Assess the efficacy of alitretinoin over time in reduction of signs (e.g. ulcerations) or symptoms (e.g. pruritus), using VAS for pruritus and pain and OHIP
Assess the time to response (time to 50 % reduction in the total Escudier score)
Assess oral mucosal changes regarding inflammation and erosions, at treatment end compared to baseline using Escudier
Assess the number/distribution of extramucosal skin lesions (papules) of LP at treatment end compared to baseline
Assess, if applicable, the inflammatory infiltrate in mucosa and skin before and during alitretinoin therapy determined by histopathology taken before and 4 weeks after initiation of study treatment.
Determine the relapse rate (relapse is defined as Escudier score or number of extramucosal papules increasing back to > 75% of baseline) within 24 week follow-up
Assess safety of alitretinoin in mucosal lichen planus for the body as a whole

Full Information

First Posted
February 20, 2012
Last Updated
March 19, 2012
Sponsor
University of Zurich
search

1. Study Identification

Unique Protocol Identification Number
NCT01538732
Brief Title
Lichen Planus Mucosae at USZ, Efficacy of Oral Alitretinoin
Official Title
Single-Center, Prospective, Open Label, Single-arm Pilot Study Investigating the Efficacy and Safety of Alitretinoin in Patients Suffering From Severe Mucosal Lichen Planus.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2012
Overall Recruitment Status
Unknown status
Study Start Date
March 2012 (undefined)
Primary Completion Date
March 2014 (Anticipated)
Study Completion Date
March 2014 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a single center, prospective, open label, single arm, investigator initiated pilot study investigating the effect of alitretinoin on severe lichen planus with mucosal manifestations. The target population comprises patients with MLP for at least 3 months, with or without LP lesions on other areas of the skin, who are refractory to topical therapy and standard skin care, and who are otherwise in good health. Patients will be recruited at the outpatient clinic of the dermatology department, University hospital Zurich.The planned duration of the study is 2 years. A total of 20 patients will be included. Patients who meet enrolment criteria will receive 30mg alitretinoin, given orally as gelatin capsules, once daily for 24 weeks. Dose interruptions are permitted in response to adverse effects, consistent with use of retinoids and the product label. Most clinical evaluations will be performed every 4 weeks. A safety follow-up visit is planned 4 weeks after the end of treatment. Further follow-up visits will be conducted 16 and 24 weeks after end of treatment in those patients meeting the primary endpoint Trial with medicinal product

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lichen Planus (LP)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
alitretinoin
Intervention Description
30mg capsules (Alitretinoin)will be taken peroral once daily with a meal. Study treatment will be given for a total duration of up to 24 weeks
Primary Outcome Measure Information:
Title
Efficacy of alitretinoin (Toctino®) based on the Escudier score of oral lesions at baseline and after 24 weeks of treatment.
Description
The primary objective is to determine the efficacy of alitretinoin (Toctino®) in reducing signs and symptoms of severe mucosal lichen planus with respect to the proportion of responders based on the, Escudier score of oral lesions at baseline and after 24 weeks of treatment or at the latest assessment for patients who withdrew prematurely (Last Observation Carried Forward, LOCF). Response is defined as a 50 % reduction in the total Escudier score compared to the baseline values.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Assess the efficacy of alitretinoin over time in reduction of signs (e.g. ulcerations) or symptoms (e.g. pruritus), using VAS for pruritus and pain and OHIP
Time Frame
6 months
Title
Assess the time to response (time to 50 % reduction in the total Escudier score)
Time Frame
6 months
Title
Assess oral mucosal changes regarding inflammation and erosions, at treatment end compared to baseline using Escudier
Time Frame
6 months
Title
Assess the number/distribution of extramucosal skin lesions (papules) of LP at treatment end compared to baseline
Time Frame
6 months
Title
Assess, if applicable, the inflammatory infiltrate in mucosa and skin before and during alitretinoin therapy determined by histopathology taken before and 4 weeks after initiation of study treatment.
Time Frame
4 weeks
Title
Determine the relapse rate (relapse is defined as Escudier score or number of extramucosal papules increasing back to > 75% of baseline) within 24 week follow-up
Time Frame
6 months
Title
Assess safety of alitretinoin in mucosal lichen planus for the body as a whole
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Aged 18 to 75 years MLP for at least 3 months Disease activity according to Escudier score of 10 points or greater or erosive lesion of any score Refractory to standard topical therapy Consensus to a 2 weeks wash-out period of topical steroids before starting study treatment Exclusion criteria Unable to comply with the requirements of the study Pregnant or lactating women Female patients of childbearing potential who cannot use or will not commit to using two effective forms of contraception simultaneously under supervision of the investigator or a gynecologist Active hepatitis and/or vaccination against hepatitis A/B during the last 4 weeks Adequate control of the disease by standard topical therapy and standard topical corticosteroid therapy Known hypersensitivity to other retinoids or vitamin A derivatives, or to any study medication component Patients treated with any of the following treatments 4 weeks before the start of study treatment: systemic drugs: corticosteroids, immunosuppressants, methotrexate phototherapy Treatment with any systemic or topical retinoids within 1 year or 1 month, respectively, before start of study treatment or treatment with systemic retinoids for treatment for MLP at any time coexistence of any serious medical condition which, in the opinion of the investigator, may interfere with the safety of the patient, including hepatic insufficiency (alanine aminotransferase and /or aspartate aminotransferase values > 2.5 x ULN) severe renal failure uncontrolled hypertriglyceridemia (triglycerides >150 % of the upper limit of normal), uncontrolled hypercholesterolemia (cholesterol or low density lipoprotein (LDL) cholesterol values > 1.5 x ULN Patients with cardiovascular risk factors that would exclude a starting dose of 30 mg of alitretinoin Uncontrolled hypothyroidism Hypervitaminosis A Active major psychiatric disorder including depression and suicidal ideation Concomitant medications such as systemic tetracyclines, CYP3A4 inhibitors such as ketoconazole, Vitamin A or St. John's Wort within 1 week, or receiving systemic itraconazole within 2 weeks, before start of study treatment Trial participation within 2 months before start of study treatment (3 months for biologics)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Johanna Mangana, MD
Email
johanna.mangana@usz.ch
First Name & Middle Initial & Last Name or Official Title & Degree
Reinhard Dummer, Professor, MD
Email
reinhard.dummer@usz.ch
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Reinhard Dummer, Prof. MD
Organizational Affiliation
University Hospital Zurich, Division of Dermatology
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital Zurich, Division of Dermatology
City
Zurich
State/Province
ZH
ZIP/Postal Code
8091
Country
Switzerland
Individual Site Status
Recruiting

12. IPD Sharing Statement

Citations:
PubMed Identifier
26507685
Citation
Kunz M, Urosevic-Maiwald M, Goldinger SM, Frauchiger AL, Dreier J, Belloni B, Mangana J, Jenni D, Dippel M, Cozzio A, Guenova E, Kamarachev J, French LE, Dummer R. Efficacy and safety of oral alitretinoin in severe oral lichen planus--results of a prospective pilot study. J Eur Acad Dermatol Venereol. 2016 Feb;30(2):293-8. doi: 10.1111/jdv.13444. Epub 2015 Oct 27.
Results Reference
derived

Learn more about this trial

Lichen Planus Mucosae at USZ, Efficacy of Oral Alitretinoin

We'll reach out to this number within 24 hrs