Lupus Erythematosus, DiscoidPhase 2TARGET-DLENCT02656082
Targeted Therapy Using Intradermal Injection of Etanercept for Remission Induction in Discoid Lupus Erythematosus
A Phase 2 study testing Etanercept in people with Lupus Erythematosus, Discoid and Lupus Erythematosus, Cutaneous, run by University of Leeds at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lupus Erythematosus, Discoid, Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Chronic Cutaneous
- What is being tested?
- Etanercept
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2016to 31 Dec 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults aged 18-80 years old.
- Have at least one active DLE lesion, either diagnosed by skin biopsy or confirmation by Dermatologist/ Rheumatologist.
- Patients with DLE only and SLE patients with DLE are included.
- Have refractory disease to an anti-malarial for at least 3 months as assessed by Dermatologist/Rheumatologist.
- 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)
- Ability to provide an informed consent.
- 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.
Who cannot join
- Any prior treatment with TNF-blockade therapies.
- Intramuscular or intra-dermal corticosteroid within 28 days of the Screening visit.
- Corticosteroid of greater than 10mg prednisolone daily equivalent, or change in oral steroid dose within 28 days prior to Baseline Visit.
- A change in the dose of other immunosuppressant including methotrexate, azathioprine and mycophenolate mofetil within 28 days (±1 day) prior to Baseline Visit.
- 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.
- Evidence of an immunosuppressive state, including an active HIV infection, agammaglobulinaemias, T-cell deficiencies or Human T cell Lymphotrophic Virus Type 1 (HTLV-1).
Show all 14Show fewer
- 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.
- 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.
- Demyelinating diseases.
- Moderate to severe heart failure based on New York Heart Association (NYHA) functional class III and IV.
- Pregnancy.
- Breastfeeding.
- Planned surgery within the study period which is expected to require omission of study medication of 28 days or more.
- Receipt of live attenuated vaccine within 28 days prior to the Baseline Visit.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Leeds Institute of Rheumatic and Musculoskeletal Medicine, Chapel Allerton Hospital
Leeds, LS7 4SA
About this study
Official title: A Single Arm, Phase II Open Label Trial to Investigate the Efficacy and Safety of Intra-dermal Injection of Etanercept for Remission Induction in Discoid Lupus Erythematosus
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.
Read the detailed description
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), thermography and laser Doppler imaging (LDI).
Data from this study may be used to power a definitive randomised controlled trial should the primary end point be achieved.
- Conditions
- Lupus Erythematosus, Discoid, Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Chronic Cutaneous
- Being tested
- Etanercept
- Keywords
- Discoid lupus erythematosus, Intradermal injection of etanercept
- Medical subject headings
- Lupus Erythematosus, Discoid, Lupus Erythematosus, Cutaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EtanerceptDrug
Also called Enbrel
Treatment with etanercept is intended for remission induction of DLE only and not for maintenance purpose.
| Study group | Role | What they receive |
|---|---|---|
| Etanercept | Experimental | Intradermal injection of etanercept. The dosage is determined based on discoid lesion radius. Weekly injection up to 12 weeks. Receives: Drug: Etanercept |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
A modified SADDLE score will be used; limited to only one index lesion and the efficacy is judged based on total score in activity component only.
Measured: At Week 12
Secondary outcomes (18)
Change in Physician's Visual Analogue Scale (VAS) for global assessment of disease activity from Baseline
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."
Measured: At Week 12
Change in daily oral prednisolone dose from Baseline
Corticosteroid doses should be converted to prednisolone-equivalent doses (if not taking prednisolone form of corticosteroid) for data analysis. Expressed in milligram (mg).
Measured: At Week 12
Change in Dermatology Life Quality Index (DLQI) from Baseline
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.
Measured: At Week 12
Change in Participant's VAS for global health assessment from Baseline
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."
Measured: At Week 12
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Measured: From Baseline to 15 weeks
Number of participants with new development or worsening of positive anti-nuclear antigen (ANA) titres from Baseline
Measured: At Week 7 and 15
Number of participants with new development or worsening of positive anti-double stranded deoxyribonucleic acid (dsDNA) titres from Baseline
Measured: At Week 7 and 15
Number of participants with new development or worsening of positive anti-extract nuclear antigen (ENA) titres from Baseline
Measured: At Week 7 and 15
Number of participants with new development or worsening of positive anti-cardiolipin antibody (ACA) titres from Baseline
Measured: At Week 7 and 15
Change in complement (C3 and C4) levels below the normal limit (if normal at baseline)
Measured: At Week 7 and 15
Number of participants with detectable serum etanercept level
Measured: At Week 5
Change in disease activity as assessed using the British Isles Lupus Activity Groups (BILAG)-2004 score from Baseline
This is only assessed in participants with systemic lupus erythematosus (SLE) rather than DLE only at Baseline
Measured: At Week 7 and 15
Change in disease activity as assessed using SLE Disease Activity Index (SLEDAI) from Baseline
This is only assessed in participants with systemic lupus erythematosus (SLE) rather than DLE only at Baseline
Measured: At Week 7 and 15
Change in total histiopathologic score of skin biopsy from Baseline
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.
Measured: At Week 12
Change in total OCT score from Baseline
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
Measured: At Week 12
Change in the difference in temperature between active DLE and nonactive area as assessed using thermography from Baseline
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
Measured: At Week 12
Change in perfusion per unit blood flow as assessed using LDI from Baseline
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 generates colour-coded images of the spatial distribution of tissue perfusion. This is expressed in terms of arbitrary perfusion units (PU).
Measured: At Week 12
Change in photograph score from Baseline
The index lesion will be photographed using macro digital camera. These images will then be scored by two dermatologists who will be blinded to the clinical status, for response to therapy using a graded scale of 1-5; 1=remission, 2=slight improvement, 3=no change in response, 4=slight worsening and 5=severe worsening.
Measured: At Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2016 (estimated)
- Study start1 Feb 2016
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lupus Erythematosus, DiscoidStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leeds
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Pfizer, Clinical Trials Research Unit, Leeds
- Responsible party
- Principal investigator, Yuzaiful Md Yusof, University of Leeds
- Investigators
- Paul Emery, MD FMedSci, Study chair, University of Leeds
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02656082
- Sponsor's protocol ID
- RR15/114
- Other IDs
- 2015-001602-33, 2015
- Acronym
- TARGET-DLE
- Status last verified
- Feb 2019
- First submitted
- 8 Jan 2016
- Last updated
- 27 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single Arm, Phase II Open Label Trial to Investigate the Efficacy and Safety of Intra-dermal Injection of Etanercept for Remission Induction in Discoid Lupus Erythematosus
- ClinicalTrials.gov ID
- NCT02656082
- Acronym / sponsor ID
- TARGET-DLE / RR15/114
- Conditions
- Lupus Erythematosus, Discoid, Lupus Erythematosus, Cutaneous, Lupus Erythematosus, Chronic Cutaneous
- Keywords
- Discoid lupus erythematosus, Intradermal injection of etanercept
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- University of LeedsUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Pfizer, Clinical Trials Research Unit, Leeds
- Study start
- 1 Feb 2016 (actual)
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 14 Jan 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 description
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), thermography and laser Doppler imaging (LDI).
Data from this study may be used to power a definitive randomised controlled trial should the primary end point be achieved.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Etanercept | Experimental | Drug: EtanerceptIntradermal injection of etanercept. The dosage is determined based on discoid lesion radius. Weekly injection up to 12 weeks. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adults aged 18-80 years old.
- Have at least one active DLE lesion, either diagnosed by skin biopsy or confirmation by Dermatologist/ Rheumatologist.
- Patients with DLE only and SLE patients with DLE are included.
- Have refractory disease to an anti-malarial for at least 3 months as assessed by Dermatologist/Rheumatologist.
- 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)
Key exclusion criteria (14 listed)
- Any prior treatment with TNF-blockade therapies.
- Intramuscular or intra-dermal corticosteroid within 28 days of the Screening visit.
- Corticosteroid of greater than 10mg prednisolone daily equivalent, or change in oral steroid dose within 28 days prior to Baseline Visit.
- A change in the dose of other immunosuppressant including methotrexate, azathioprine and mycophenolate mofetil within 28 days (±1 day) prior to Baseline Visit.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EtanerceptAlso: EnbrelTreatment with etanercept is intended for remission induction of DLE only and not for maintenance purpose. | Drug | Etanercept |
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
A modified SADDLE score will be used; limited to only one index lesion and the efficacy is judged based on total score in activity component only.
18 secondary outcomes
Change in Physician's Visual Analogue Scale (VAS) for global assessment of disease activity from Baseline
Time frame: At Week 12
Change in daily oral prednisolone dose from Baseline
Time frame: At Week 12
Change in Dermatology Life Quality Index (DLQI) from Baseline
Time frame: At Week 12
Change in Participant's VAS for global health assessment from Baseline
Time frame: At Week 12
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
Change in disease activity as assessed using SLE Disease Activity Index (SLEDAI) from Baseline
Time frame: At Week 7 and 15
Change in total histiopathologic score of skin biopsy from Baseline
Time frame: At Week 12
Change in total OCT score from Baseline
Time frame: At Week 12
Change in the difference in temperature between active DLE and nonactive area as assessed using thermography from Baseline
Time frame: At Week 12
Change in perfusion per unit blood flow as assessed using LDI from Baseline
Time frame: At Week 12
Change in photograph score from Baseline
Time frame: At Week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2019.
Related trials for Lupus Erythematosus, Discoid
RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease
Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE)
RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease (ELOWEN-2)
Systematic Lupus Erythematosus, Cutaneous Lupus Erythematosus
RecruitingPhase 2/3
Study of Afimetoran in Adults With Cutaneous Lupus Erythematosus
Cutaneous Lupus Erythematosus (CLE), Systematic Lupus Erythematosus
Active, not recruitingPhase 2/3
A 2-Part Study to Learn Whether Litifilimab (BIIB059) Injections Can Improve Symptoms of Adult Participants Who Have Active Cutaneous Lupus Erythematosus
Subacute Cutaneous Lupus Erythematosus, Chronic Cutaneous Lupus Erythematosus
Active, not recruitingPhase 2
The Willow LTE Study With M5049 in Participants With SCLE, DLE and/or SLE (WILLOW LTE)
Systemic Lupus Erythematosus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Emery, MD FMedSci study chair
University of Leeds
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Etanercept in people with Lupus Erythematosus, Discoid and Lupus Erythematosus, Cutaneous, run by University of Leeds at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2019.