Discoid lupus erythematosus MedDRA version: 18.0 Level: LLT Classification code 10013072 Term: Discoid lupus erythematosus System Organ Class: 100000004858
Conditions
Interventions
Trade Name: Enbrel 10 mg powder and solvent for solution for injection
Product Name: Etanercept
Product Code: EU/1/99/126/022
Pharmaceutical Form: Powder and solvent for solution for injection
INN or
Sponsors
The University of Leeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: (i) Adults aged 18-65 years old. (ii) Have at least one active DLE lesion, either diagnosed by skin biopsy or confirmation by Consultant Dermatologist/Rheumatologist. (iii) Patients with DLE only and SLE patients with DLE are included. (iv) Have refractory disease to an anti-malarial at 3 months as assessed by the Dermatologist/Rheumatologist. (v) Patients receiving anti-malarials must have been receiving them for at least 3 months prior to Screening, with a stable dose regimen for at least 28 days (±1 day) prior to Baseline (the first study drug administration) (vi) Ability to provide an informed consent. (vii) All male and female patients biologically capable of having children must agree to use a reliable method of contraception for the duration of the study and for a period of 3 weeks after their final dose of study drug. Acceptable methods of contraception are surgical sterilisation, oral, implantable or injectable hormonal methods, intrauterine devices or barrier contraceptives. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: (i) Any prior treatment with TNF-blockade therapies. (ii) Intramuscular or intra-dermal corticosteroid within 28 days of the Screening visit. (iii) Oral steroid of greater than 10mg prednisolone daily, or change in oral steroid dose within 28 days prior to the Baseline Visit. (iv) A change in the dose of other immunosuppressant including methotrexate, azathioprine and mycophenolate mofetil within 28 days (±1 day) prior to Baseline Visit. (v) Concomitant therapies with any alkylating agents (e.g. cyclophosphamide, chlorambucil), other immunosuppressant including sulfasalazine and leflunomide, other biological agent particularly anakinra and abatacept and other experimental drug. If patients are on any of these, they need to be off therapies for at least 28 days prior to Baseline Visit to allow for washout. (vi) Evidence of an immunosuppressive state, including an active HIV infection, agammaglobulinaemia, T-cell deficiencies or Human T cell Lymphotrophic Virus Type 1 (HTLV-1). (vii) Chronic active infection such as hepatitis B or hepatitis C and tuberculosis. Patients with latent tuberculosis may be included if treated with chemoprophylaxis for at least 2 months before starting the study and to continue chemoprophylaxis for a total of 6 months (viii) History of cancer within the last 5 years except for squamous or basal cell skin carcinoma that has been completely excised and treated cervical carcinoma in situ. (ix) Demyelinating diseases. (x) Moderate to severe heart failure based on New York Heart Association (NYHA) functional class III and IV. (xi) Pregnancy. (xii) Breastfeeding. (xiii) Planned surgery within the study period which is expected to require omission of study medication of 28 days or more. (xiv) Receipt of live attenuated vaccine within 28 days prior to the Baseline Visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the proportion of patients with active discoid lupus erythematosus (DLE) that achieves a clinical response as assessed using the modified Limited Score of Activity and Damage in DLE (SADDLE) tool (ie: defined as reduction in modified limited SADDLE score by 20% or more from baseline in the discoid lesion) at Week 12 following treatment with weekly intra-dermal injection of etanercept.;Secondary Objective: (i) To assess other efficacy outcomes including Physician’s rating of patient's disease activity using the Visual Analogue Scale (VAS) and daily oral corticosteroid requirement (ii) To assess patient-reported outcomes including Dermatology Life Quality Index (DLQI)Questionnaire and Patient’s rating of his/her disease activity using the VAS (iii) To report the safety of treatment in terms of side effects and/or reaction to the drug. We will also report whether the treatment leads to progression of patients with DLE only (skin involvement only) to widespread involvement of lupus symptoms; systemic lupus erythematosus (SLE) or makes the patients who are already known SLE worse (iv) To assess whether intra-dermal injection of etanercept is associated with absorption of the drug in the blood (v) To report whether the patients are willing to undergo the four tests to measure skin inflammation (a) skin biopsy, (b) optical coherence tomography (OCT), (c) infrared thermography and (d) laser;Primary end point(s): Reduction in the modified limited Score of Activity and Damage in DLE (SADDLE) score by 20% or more from baseline in the index lesion at Week 12.;Timepoint(s) of evaluation of this end point: 12 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Change in Physician’s VAS and daily oral corticosteroid requirement at Week 12. 2. Change in patient-reported outcomes; DLQI and Patient’s VAS at Week 12. 3. Incidence of AEs, ARs, SAEs, SARs and SUSARs. 4. New development or worsening of positive auto-antibodies titres: anti-nuclear antigen (ANA) and anti-double stranded deoxyribonucleic acid (dsDNA), extractable nuclear antigen antibodies (anti-ENAs) and anti-cardiolipin antibody (ACA) at Week 7 and 15. 5. Change in complement (C3 and C4) levels below the normal limit (if normal at baseline) at Week 7 and 15. 6. For SLE patients, change in disease activity as assessed using the British Isles Lupus Activity Groups (BILAG)-2004 score and SLE Disease Activity Index (SLEDAI) at Week 7 and 15. 7. Objective assessment of tissue response using (i) histopathology from skin biopsy – change in grade of histopathologic features (ii) OCT – change in OCT parameters (iii) Infrared thermography – change in the difference in temperature between active DLE and non-active areas and (iv) LDI – change in perfusion per unit blood flow. 8. Validity of photograph of lesion as an outcome measure. Exploratory endpoints: 1.The proportion of patients who are willing to undergo skin biopsy, OCT, thermography and LDI assessments pre- and post-therapy 2. Correlation of OCT, thermography, LDI and photograph with the modified limited SADDLE score 3. Sensitivity and specificity of OCT, thermography, LDI and photograph against the gold standard; histopathologic features from skin biopsy as an outcome measure ;Timepoint(s) of evaluation of this end point: As above at Week 12. However for safety end points (Number 3-6), these will be evaluated at Week 15. | — |
Countries
United Kingdom
Contacts
Public ContactJames Goulding
University of Leeds
Outcome results
None listed