E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
severe oral lichen planus (LP) with variable phenotype (erosive, ulcerating, hyperplastic/leucoplastic, and combined forms) |
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E.1.1.1 | Medical condition in easily understood language |
severe oral skin disease lichen planus (LP) with variable outer appearance |
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E.1.1.2 | Therapeutic area | Diseases [C] - Skin and Connective Tissue Diseases [C17] |
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 |
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) |
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E.2.2 | Secondary objectives of the trial |
Pharmacodynamics, Association between the mechanistical responders/ improvement and the clinical improvement, Quality of Life, Safety, immunological read outs |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
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E.4 | Principal 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) |
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E.5 End points |
E.5.1 | 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. The responder rates will be compared between the two groups (waiting list and verum)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Pharmcodynamics 2)Association between the mechanistical responders/ improvement and the clinical improvement 3)Quality of Life 4)Safety Immunolgical read-outs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Pharmacodynamics of Guselkumab in patients with oral LP (Week 0 vs. 12 and 24) 2. Association between the mechanistical responders/ improvement and the clinical improvement (comparison week 12 and 24) 3. Quality of Life (Patient reported Outcomes) in patients with oral LP treated with Guselkumab (Weeks 0, 4, 12, 20, 24) 4. Safety (throughout 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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life, Imunolgical readouts: T cell subpopulations (e.g. CD4, CD8, IFN-γ, IL-17) within lesional biopsies; peripheral blood T cell subpopulations (e.g. Th1-, Th17-cells), safety |
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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 | No |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |