Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.

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

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).

Study Overview

• Status: Terminated
• Conditions: Discoid Lupus Erythematosus
• Intervention / Treatment: Drug: Delgocitinib cream vehicle; Drug: Delgocitinib cream

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • LEO Pharma Investigational Site
  • Hellerup, Denmark, 2900
    • LEO Pharma Investigational Site
  • Odense, Denmark, 5000
    • LEO Pharma Investigational Site
• France
  • Loiré, France, 42000
    • LEO Pharma Investigational Site
  • Nice, France, 06202
    • LEO Pharma Investigational Site
  • Paris, France, 75010
    • LEO Pharma Investigational Site
  • Toulouse, France, 31000
    • LEO Pharma Investigational Site
• Germany
  • Aachen, Germany, 52074
    • LEO Pharma Investigational Site
  • Berlin, Germany, 10117
    • LEO Pharma Investigational Site
  • Bochum, Germany, 44791
    • LEO Pharma Investigational Site
  • Dresden, Germany, 01307
    • LEO Pharma Investigational Site
  • Duesseldorf, Germany, 40225
    • LEO Pharma Investigational Site
  • Erlangen, Germany, 91054
    • LEO Pharma Investigational Site
  • Oldenburg, Germany, 26133
    • LEO Pharma Investigational Site
• United States
  • California
    • San Diego, California, United States, 92103
      • LEO Pharma Investigational Site
  • Illinois
    • Skokie, Illinois, United States, 60077
      • LEO Pharma Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • LEO Pharma Investigational Site
  • New York
    • Forest Hills, New York, United States, 11375
      • LEO Pharma Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: LEO Pharma

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2019
• Primary Completion (Actual): April 15, 2020
• Study Completion (Actual): April 30, 2020

Study Registration Dates

• First Submitted: May 20, 2019
• First Submitted That Met QC Criteria: May 20, 2019
• First Posted (Actual): May 22, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2021
• Last Update Submitted That Met QC Criteria: June 4, 2021
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Cutaneous; Lupus Erythematosus, Systemic; Lupus Erythematosus, Discoid
• Other Study ID Numbers: EXP-1373; 2018-003615-22 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

De-identified individual patient data (IPD) can be made available to researchers in a closed environment for a specified period of time.

Data sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.

• IPD Sharing Time Frame: Data is available to request after approval of the studied indication.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No