Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.
Condition: Discoid Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic; Lupus Erythematosus, Discoid
Intervention: Delgocitinib cream; Delgocitinib cream vehicle
Intervention description: Cream for topical application.; The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention 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 (Participant, Investigator)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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.