Clinical Trial: Targeted Therapy Using Intradermal Injection of Etanercept for Remission Induction in Discoid Lupus Erythematosus
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: A Single Arm, Simon's 2-stage Minimax Design, Phase II Open Label Trial to Investigate the Efficacy and Safety of Intra-dermal Injection of Etanercept for Remission Induction in
Brief Summary:
The purpose of this study is to determine whether Etanercept which is given through intradermal injection is effective in the treatment of discoid lupus erythematosus (DLE).
The investigators also would like to develop new tests to measure skin inflammation by scanning the affected skin using optical coherence tomography (OCT), thermography and laser doppler imaging (LDI) and taking photographs of the rash (to be done before and after treatment). If the findings from these new tests are similar to the ones from taking a sample of skin (biopsy), then the latter (which is an invasive test) can be avoided.
Detailed Summary:
There is an unmet need for new therapies to control inflammation in discoid lupus erythematosus (DLE). A significant proportion of DLE patients (with or without systemic lupus erythematosus (SLE)) are resistant to conventional therapies and DLE may be exacerbated by B cell depletion therapy.There is no clinical guideline or algorithm on how to manage patients with DLE who have refractory disease to the first line agents, anti-malarials. If left untreated, uncontrolled inflammation will lead to permanent disfiguring and irreversible scar to the patient, thus pose a major cosmetic issue and significantly impair the quality of life.
Targeted therapy based on immunopathogenesis is an attractive approach and tumour necrosis factor (TNF) is implicated in the pathogenesis of DLE. However, systemic administration of TNF blockers has been associated with induction of pathogenic autoantibodies that may render SLE worse or progression from DLE only to SLE. TNF blockers have been administered using the intra-dermal injection route in other TNF-mediated diseases and appear similarly safe and effective to systemic administration.
Another issue is the problem with outcome measures as skin disease is particularly heterogenous and many instruments rely on subjective assessment which may be difficult even in the hands of experts.
The TARGET-DLE trial will address these problems by: (i) administering a TNF blocker, etanercept using the intra-dermal route, which will provide local concentration to neutralise TNF in tissue while minimises the effect to systemic immunity and (ii) measuring tissue response using the existing outcome measure; the modified limited Score of Activity and Damage in DLE (SADDLE) as well as new objective measures such as skin biopsy, optical coherence tomography (OCT),
Sponsor: University of Leeds
Current Primary Outcome: The proportion of patients who achieve a reduction in the modified limited Score of Activity and Damage in Discoid Lupus Erythematosus (SADDLE) score by 20% of the baseline score in the index lesion [ Time Frame: At Week 12 ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Change in Physician's Visual Analogue Scale (VAS) for global assessment of disease activity from Baseline [ Time Frame: At Week 12 ]The investigator will rate the overall disease activity status of the participant with respect to the DLE signs and symptoms and the functional capacity of the participant, using a 100mm VAS where 0 is "very good, asymptomatic, and no limitation of normal activities" and 100 is "very poor, very severe symptoms which are intolerable, and inability to carry out all normal activities."
- Change in daily oral prednisolone dose from Baseline [ Time Frame: At Week 12 ]Corticosteroid doses should be converted to prednisolone-equivalent doses (if not taking prednisolone form of corticosteroid) for data analysis. Expressed in milligram (mg).
- Change in Dermatology Life Quality Index (DLQI) from Baseline [ Time Frame: At Week 12 ]This participant-reported outcome consists of 10 questions concerning participants' perception of the impact of skin diseases on different aspects of their health related quality of life over the preceding week.
- Change in Participant's VAS for global health assessment from Baseline [ Time Frame: At Week 12 ]Participants will rate their global assessment of their DLE disease activity for the day of the visit using a 100mm VAS where 0 is "very good, no symptoms" and 100 is "very poor, very severe symptoms."
- Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: From Baseline to 15 weeks ]
- Number of participants with new development or worsening of positive anti-nuclear antigen (ANA) titres from Baseline [ Time Frame: At Week 7 and 15 ]
- Number of participants with new development or worsening of positive anti-double stranded deoxyribonucleic acid (dsDNA) titres from Baseline [ Time Frame: At Week 7 and 15 ]
- Number of participants with new development or worsening of positive anti-extract nuclear antigen (ENA) titres from Baseline [ Time Frame: At Week 7 and 15 ]
- Number of participants with new development or worsening of positive anti-cardiolipin antibody (ACA) titres from Baseline [ Time Frame: At Week 7 and 15 ]
- Change in complement (C3 and C4) levels below the normal limit (if normal at baseline) [ Time Frame: At Week 7 and 15 ]
- Number of participants with detectable serum etanercept level [ Time Frame: At Week 5 ]
- Change in disease activity as assessed using the British Isles Lupus Activity Groups (BILAG)-2004 score from Baseline [ Time Frame: At Week 7 and 15 ]This is only assessed in participants with systemic lupus erythematosus (SLE) rather than DLE only at Baseline
- Change in disease activity as assessed using SLE Disease Activity Index (SLEDAI) from Baseline [ Time Frame: At Week 7 and 15 ]This is only assessed in participants with systemic lupus erythematosus (SLE) rather than DLE only at Baseline
- Change in total histiopathologic score of skin biopsy from Baseline [ Time Frame: At Week 12 ]The skin biopsy will be scored for the classic histological features of DLE including (i) interface dermatitis (ii) vacuolar alteration of the basal layer, (iii) thickening of the basement membrane, (iv) follicular plugging, (v) hyperkeratosis, (vi) atrophy of the epidermis, (vii) inflammatory cell infiltrate in a perivascular, periappendageal and subepidermal location and (viii) dermal mucin deposition using a graded scale of 0-3; 0=none, 1=slight, 2=moderate and 3=strong for each feature.
- Change in total OCT score from Baseline [ Time Frame: At Week 12 ]The OCT will be scored for (i) thickening and disruption of the entrance signal (ii) thinning of layer below the entrance signal (iii) patchy hyporeflective zones in the epidermis and (iv) wide signal free cavities in the upper dermis using a graded scale of 0-3; 0=none, 1=slight, 2=moderate and 3=strong for each parameter
- Change in the difference in temperature between active DLE and nonactive area as assessed using thermography from Baseline [ Time Frame: At Week 12 ]Thermography is a non-invasive technique that detects infrared radiation to provide an image of the temperature distribution across skin surface. The temperature will be measured in Celcius
- Change in perfusion per unit blood flow as assessed using LDI from Baseline [ Time Frame: At Week 12 ]LDI is a non-invasive imaging modality that is used to monitor blood perfusion in dermal tissue. Based on the well-established Doppler principle, this beam collects back-scattered light without touching the tissue and
Original Secondary Outcome: Same as current
Information By: University of Leeds
Dates:
Date Received: January 8, 2016
Date Started: February 2016
Date Completion: December 2017
Last Updated: October 24, 2016
Last Verified: October 2016
