Clinical trial NCT03958955: Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.
Official title: Efficacy and Safety of Twice-daily Application of Delgocitinib Cream 20 mg/g for 6 Weeks in Subjects With Active Discoid Lupus Erythematosus.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Discoid Lupus Erythematosus
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2019-05-22
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Target Lesions With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 6.
timeFrame: Week 6
Secondary outcomes:
measure: Number of Adverse Events (AEs) up to Week 6.
timeFrame: Week 0 to Week 6
measure: Number of Subjects With AEs up to Week 6.
timeFrame: Week 0 to Week 6
measure: Number of Lesion-specific, Treatment-related AEs up to Week 6.
timeFrame: Week 0 to Week 6
measure: Number of Lesions With ≥2-point Reduction in IGA Score at Week 6 Compared to Baseline.
timeFrame: Week 0 to Week 6
measure: Number of Lesions With ≥2-point Reduction in Erythema Score at Week 6 Compared to Baseline.
timeFrame: Week 0 to Week 6
measure: Erythema Score at Week 6.
timeFrame: Week 6
measure: Total Skin Disease Activity Score (Sum of Scores for Erythema, Scaling/Hyperkeratosis, and Oedema/Infiltration) at Week 6.
timeFrame: Week 6
Other outcomes:
Locations:
city: San Diego
country: United States
facility: LEO Pharma Investigational Site
state: California
city: Skokie
country: United States
facility: LEO Pharma Investigational Site
state: Illinois
city: Boston
country: United States
facility: LEO Pharma Investigational Site
state: Massachusetts
city: Forest Hills
country: United States
facility: LEO Pharma Investigational Site
state: New York
city: Cincinnati
country: United States
facility: LEO Pharma Investigational Site
state: Ohio
city: Aarhus
country: Denmark
facility: LEO Pharma Investigational Site
city: Hellerup
country: Denmark
facility: LEO Pharma Investigational site
city: Odense
country: Denmark
facility: LEO Pharma Investigational Site
city: Loiré
country: France
facility: LEO Pharma Investigational Site
city: Nice
country: France
facility: LEO Pharma Investigational Site
city: Paris
country: France
facility: LEO Pharma Investigational Site
city: Toulouse
country: France
facility: LEO Pharma Investigational Site
city: Aachen
country: Germany
facility: LEO Pharma Investigational Site
city: Berlin
country: Germany
facility: LEO Pharma Investigational Site
city: Bochum
country: Germany
facility: LEO Pharma Investigational Site
city: Dresden
country: Germany
facility: LEO Pharma Investigational Site
city: Duesseldorf
country: Germany
facility: LEO Pharma Investigational Site
city: Erlangen
country: Germany
facility: LEO Pharma Investigational Site
city: Oldenburg
country: Germany
facility: LEO Pharma Investigational Site
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References:
citation: Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.