Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.

Study Overview
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Brief Summary
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This was a double-blind, multi-centre, randomised, vehicle-controlled, within-subject phase 2a trial. The trial was designed to establish the efficacy and safety of delgocitinib cream in the treatment of adult subjects with discoid lupus erythematosus (DLE).

Official Title
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Efficacy and Safety of Twice-daily Application of Delgocitinib Cream 20 mg/g for 6 Weeks in Subjects With Active Discoid Lupus Erythematosus.

Conditions
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Discoid Lupus Erythematosus

Intervention / Treatment
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* Drug: Delgocitinib cream
* Drug: Delgocitinib cream vehicle


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Histopathological findings (current or previous) consistent with clinical diagnosis of DLE. Unequivocal clinical diagnosis of 2 active DLE target lesions that were <6 months old and amenable for clinical evaluation. This included lesions located on the scalp if they fulfilled all lesion-specific eligibility criteria. Target lesion IGA score of at least moderate severity (≥3) at screening and baseline. Target lesion erythema score ≥2 at screening and baseline. Main Exclusion Criteria: Target lesion dyspigmentation score of 2 at screening or baseline. Target lesion scarring/atrophy score of 2 at screening or baseline. Target lesion scarring alopecia score of >0 in scalp lesions at screening or baseline. Medical history of systemic lupus erythematosus (SLE) with clinically significant organ involvement (American College of Rheumatology SLE classification criteria no. 6 to 9) including SLE-related pleuritis or pericarditis (by clinical evaluation and electrocardiogram), and neurologic, renal, and/or other major SLE-related organ system involvement. SLE joint involvement was acceptable. Subjects with unstable or significant SLE disease activity findings that would, by its progressive nature and/or severity, interfere with the trial evaluation, completion, and/or procedures per the investigator's discretion. Other skin conditions at screening or baseline that would interfere with the evaluation of DLE. Immunosuppressive/immunomodulating therapy with e.g. methotrexate, cyclosporine, azathioprine, retinoids (both topical and systemic), or dapsone within 4 weeks prior to baseline. Systemic prednisolone >7.5 mg/day or changed dose within 4 weeks prior to baseline (nasal and inhaled corticosteroids were allowed). Treatment with the following medications: Oral antimalarial treatment with hydroxychloroquine >6.5 mg/kg body weight/day, or chloroquine >4 mg/kg body weight/day, or changed dose within 12 weeks prior to baseline. Quinacrine combined with either hydroxychloroquine or chloroquine within 12 weeks prior to baseline. Drugs known to interact with antimalarials (e.g. digoxin, cimetidine) within 12 weeks prior to baseline. Treatment with topical corticosteroids, calcineurin inhibitors, and phosphodiesterase-4 (PDE-4) inhibitors within 2 weeks prior to baseline. Use of systemic antibiotics or cutaneously applied antibiotics on the target lesions within 2 weeks prior to baseline. Ultraviolet (UV) therapy within 2 weeks prior to baseline. Any procedure impairing the skin barrier (e.g. incision) within 2 cm from the border of any of the target lesions within 4 weeks prior to baseline. Receipt of live (attenuated) vaccines within 4 weeks prior to baseline. Treatment with any marketed biological therapy or investigational biologic agents: Any cell-depleting agents including but not limited to rituximab: within 6 months prior to baseline, or until lymphocyte count returned to normal, whichever was longer. Other biologics: within 3 months or 5 half-lives, whichever was longer, prior to baseline. Unstable or fluctuating use of tobacco within 1 month prior to screening which, in the opinion of the investigator, could affect the natural course of the disease and thus affect the evaluation of the treatment. History of any active skin infection within 1 week prior to baseline. Clinically significant infection within 4 weeks prior to baseline which, in the opinion of the investigator, could compromise the safety of the subject in the trial, interfere with evaluation of the IMP, or reduce the subject's ability to participate in the trial. Clinically significant infections are defined as: A systemic infection. A serious skin infection requiring parenteral (intravenous or intramuscular) antibiotics, antiviral, or antifungal medication. Tuberculosis requiring treatment within 12 months prior to screening and/or subjects with a positive blood test for tuberculosis at screening. Subjects with high risk of latent tuberculosis (e.g. prior residence in or travel to countries with high prevalence of tuberculosis, close contact with a person with active tuberculosis, or a history of active or latent tuberculosis where an adequate course of treatment cannot be confirmed) must have been tested at screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This was a phase 2a, within-subject trial design, where all subjects were treated with active treatment on one DLE target lesion and vehicle treatment on another DLE target lesion.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Delgocitinib cream 20 mg/g<br>Delgocitinib cream applied twice daily for 6 weeks | Drug: Delgocitinib cream<br>* Cream for topical application.<br>* Other names: LEO 124249 cream;|
| Placebo Comparator: Delgocitinib cream vehicle<br>Delgocitinib cream vehicle applied twice daily for 6 weeks | Drug: Delgocitinib cream vehicle<br>* The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.<br>* Other names: LEO 124249 cream vehicle;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target Lesions With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 6. | The IGA is an instrument used in clinical trials to rate the severity of the subject's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). In this trial, the IGA was a lesion-specific assessment and was evaluated separately for each of the 2 target lesions. | Week 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events (AEs) up to Week 6. | Number of AEs from baseline to Week 6 | Week 0 to Week 6 | 
| Number of Subjects With AEs up to Week 6. | Number of subjects with AEs from baseline to Week 6 | Week 0 to Week 6 | 
| Number of Lesion-specific, Treatment-related AEs up to Week 6. | The number of lesion-specific, treatment-related AEs per target lesion will be compared for active and vehicle treatment. Lesion-specific AEs are defined as lesional/perilesional AEs (i.e. AE location within the treatment area and/or ≤2 cm from the border of a target lesion). | Week 0 to Week 6 | 
| Number of Lesions With ≥2-point Reduction in IGA Score at Week 6 Compared to Baseline. | The IGA is an instrument used in clinical trials to rate the severity of the subject's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). In this trial, the IGA was a lesion-specific assessment and was evaluated separately for each of the 2 target lesions. | Week 0 to Week 6 | 
| Number of Lesions With ≥2-point Reduction in Erythema Score at Week 6 Compared to Baseline. | The erythema score is lesion-specific and based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) and the Revised CLASI (RCLASI) which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The severity of the erythema is scored on a 4-point scale ranging from 0 to 3. The severity is scored from low to high with 0=absent and 3=dark red, purple/violaceous/crusted/haemorrhagic. | Week 0 to Week 6 | 
| Erythema Score at Week 6. | The erythema score is lesion-specific and based on the CLASI and the RCLASI which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The severity of the erythema is scored on a 4-point scale ranging from 0 to 3. The severity is scored from low to high with 0=absent and 3=dark red, purple/violaceous/crusted/haemorrhagic. | Week 6 | 
| Total Skin Disease Activity Score (Sum of Scores for Erythema, Scaling/Hyperkeratosis, and Oedema/Infiltration) at Week 6. | The skin disease activity scores are based on the CLASI and the RCLASI which are validated scoring systems to assess disease activity and damage in patients with cutaneous lupus erythematosus. The total skin disease activity score is defined as the sum of the scores for 3 clinical signs (erythema, scaling/hyperkeratosis, oedema/infiltration) for each target lesion. For the total score and the individual clinical signs, higher scores indicate more severe symptoms. Erythema is scored on a 4-point scale ranging from 0 (absent) to 3 (dark red, purple/violaceous/crusted/haemorrhagic). Hyperkeratosis/scaling is scored on a 3-point scale from 0 (absent) to 2 (verrucous hyperkeratosis). Oedema/infiltration is scored on a 3-point scale from 0 (absent) to 2 (palpable and visible). The total skin disease activity score can therefore range from 0 to 7. | Week 6 |