Immunotherapy with the bioactive substance Guselkumab in patients suffering from oral skin disease Lichen-Planus using an open-label, parallel, multi-center phase IIa trial desig

Phase 1

Conditions: severe oral lichen planus (LP) with variable phenotype (erosive, ulcerating, hyperplastic/leucoplastic, and combined forms)
Therapeutic area: Diseases [C] - Skin and Connective Tissue Diseases [C17]
MedDRA version: 20.1Level: PTClassification code 10030983Term: Oral lichen planusSystem Organ Class: 10017947 - Gastrointestinal disorders

Registration Number: EUCTR2021-000271-36-DE

Lead Sponsor: Philipps University Marburg

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 45

Inclusion Criteria

1.Signed written informed consent form
2.Capability and willingness to comply with study procedures
3.Adult patients = 18 years
4.Moderate to severe Oral LP with variable phenotype (erosive, ulcerating, hyperplastic/leukoplakic, and combined forms and other side manifestations like skin manifestations)
5.Oral involvement = 3 month
6.Escudier-Score = 10
7.Histology characteristic for LP
8.Refractory to topical therapy with high-potency glucocorticoids (group I, II, III as per WHO definition)
9.For women of child-bearing potential: a negative result in a pregnancy test AND agreement to practice a highly effective method of contraception during the entire period from informed consent up to 90 days after the last administration of the IMP.
10.For non-sterilised males who are sexually active with a female partner of child-bearing potential: Agreement to practice highly effective methods of contraception during the entire period from first study intervention up to 90 days after the last administration of the IMP

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1.1.Subjects with either a chronic infection, a prior history of recurrent infection, or a clinically important active infection (e.g. active tuberculosis) should not be administered Guselkumab.
2.History of latent tuberculosis
3.Patients with clinical relevant illnesses (e.g. severe renal, heart and/ or liver insufficiency, malignancies) and clinical relevant changes in lab parameter (e.g. WBC, absolute neutrophile count, hemoglobin, AST/ALT, bilirubin)
4.History of any malignancy or obligatory precancerous condition of any organ system other than cervical carcinoma of Stage 1B or less, or non-invasive basal cell carcinoma of the skin in the last 5 years before IMP administration
5.Patients tested positive for hepatitis B virus (HBV) infection, hepatitis C virus (HCV) or human immunodeficiency viruses (HIV)
6.Systemic/topical glucocorticoids of high - ultrahigh potency (group I, II, III as per WHO definition) within 4 weeks days prior to treatment*
7.Severe hypersensitivity, intolerance or allergy against Guselkumab, to human immunoglobulin (Ig) proteins, mAbs, or antibody fragments
8.Live or inactive vaccine within the 28 days before first study treatment, or a planned vaccination during the study. NOTE: SARS-CoV2 and influenza vaccinations may be performed at the earliest 28 days before or after the last IMP treatment
9.Breastfeeding
10.Concomitant therapy with immunosuppressive drugs, biologics or phototherapy
11.Patients with an increased risk of respiratory infections (e.g. patients with chronic obstructive pulmonary disease)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: Efficacy of Guselkumab treatment on mucosal T-cell infiltration 12 weeks after study entry in patients with oral lichen planus (LP) with different phenotypes (erosive, ulcerative, hyperplastic / leukoplastic and combined forms) ;Secondary Objective: Pharmacodynamics, Association between the mechanistical responders/ improvement and the clinical improvement, Quality of Life, Safety, immunological read outs ;Primary end point(s): The primary endpoint is the proportion of patients who experience a 50% reduction in the relative number (of total CD3+ T cells) of IL-17+ CD4+ and IL-17+ CD8+ T cells in mucosal biopsies at week 12 compared to week 0 (pre-treatment). For the sake of simplicity, these patients will be called responders” in the statistical section.<br>The responder rates will be compared between the two groups (waiting list and verum)<br>;Timepoint(s) of evaluation of this end point: week 12

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Pharmcodynamics<br>2)Association between the mechanistical responders/ improvement and the clinical improvement <br>3)Quality of Life <br>4)Safety<br>Immunolgical read-outs<br><br>;Timepoint(s) of evaluation of this end point: 1.Pharmacodynamics of Guselkumab in patients with oral LP (Week 0 vs. 12 and 24)<br>2.Association between the mechanistical responders/ improvement and the clinical improvement (comparison week 12 and 24)<br>3.Quality of Life (Patient reported Outcomes) in patients with oral LP treated with Guselkumab (Weeks 0, 4, 12, 20, 24)<br>4.Safety (throughout study)<br>