Efficacy and Safety of Delgocitinib Cream in Discoid Lupus Erythematosus.

• Sponsor: LEO Pharma
• Information provided by (Responsible Party): LEO Pharma

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Discoid Lupus Erythematosus	Drug: Delgocitinib cream; Drug: Delgocitinib cream vehicle	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: This is a within-subject trial design, where all subjects will be treated with active treatment on one DLE target lesion and vehicle treatment on another DLE target lesion.
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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.
• Actual Study Start Date: June 11, 2019
• Estimated Primary Completion Date: December 2019
• Estimated Study Completion Date: December 2019

Arms and Interventions

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 Name: 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 Name: LEO 124249 cream vehicle

Outcome Measures

Primary Outcome Measures :

1. Target lesions with Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 6. [ Time Frame: Week 0 to 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 is a lesion-specific assessment and will be evaluated separately for each of the 2 target lesions.

Secondary Outcome Measures :

1. Number of adverse events (AEs) up to Week 6. [ Time Frame: Week 0 to Week 6 ]
   (Number of AEs per subject)
2. Number of subjects with AEs up to Week 6. [ Time Frame: Week 0 to Week 6 ]
   (Subjects with 1 or more AEs)
3. Number of lesion-specific, treatment-related AEs up to Week 6. [ Time Frame: Week 0 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).
4. A ≥2-point reduction in IGA score at Week 6 compared to baseline. [ Time Frame: Week 0 to 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 is a lesion-specific assessment and will be evaluated separately for each of the 2 target lesions.
5. A ≥2-point reduction in erythema score at Week 6 compared to baseline. [ Time Frame: Week 0 to week 6 ]
   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.
6. Erythema score at Week 6. [ Time Frame: Week 0 to 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.
7. Total skin disease activity score (sum of scores for erythema, scaling/hyperkeratosis, and oedema/infiltration) at Week 6. [ Time Frame: Week 0 to Week 6 ]
   The 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.

Eligibility Criteria

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

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 are <6 months old and amenable for clinical evaluation. This includes lesions located on the scalp if they fulfil 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 is 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 are 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 returns to normal, whichever is longer.
  • Other biologics: within 3 months or 5 half-lives, whichever is longer, prior to baseline.
• Smoking of >70 cigarettes/week or >70 g of tobacco content/week within 1 month prior to screening.
• 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, may 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 be tested at screening.

Contacts and Locations

Contacts

Contact: LEO Pharma A/S; (+1) 877-557-1168; disclosure@leo-pharma.com

Locations

United States, California

LEO Pharma Investigational Site; Not yet recruiting

San Diego, California, United States, 92103

United States, Illinois

LEO Pharma Investigational Site; Not yet recruiting

Skokie, Illinois, United States, 60077

United States, Massachusetts

LEO Pharma Investigational Site; Not yet recruiting

Boston, Massachusetts, United States, 02115

United States, New York

LEO Pharma Investigational Site; Not yet recruiting

Forest Hills, New York, United States, 11375

United States, Ohio

LEO Pharma Investigational Site; Not yet recruiting

Cincinnati, Ohio, United States, 45219

Denmark

LEO Pharma Inve; Not yet recruiting

Hellerup, Denmark, 2900

LEO Pharma Investigational Site; Recruiting

Odense, Denmark, 5000

France

LEO Pharma Investigational Site; Not yet recruiting

Loiré, France, 42000

LEO Pharma Investigational Site; Not yet recruiting

Nice, France, 06202

LEO Pharma Investigational Site; Not yet recruiting

Paris, France, 75010

LEO Pharma Investigational Site; Not yet recruiting

Toulouse, France, 31000

Germany

LEO Pharma Investigational Site; Not yet recruiting

Aachen, Germany, 52074

LEO Pharma Investigational Site; Not yet recruiting

Berlin, Germany, 10117

LEO Pharma Investigational Site; Not yet recruiting

Bochum, Germany, 44791

LEO Pharma Investigational Site; Recruiting

Dresden, Germany, 01307

LEO Pharma Investigational Site; Not yet recruiting

Duesseldorf, Germany, 40225

LEO Pharma Investigational Site; Recruiting

Erlangen, Germany, 91054

LEO Pharma Investigational Site; Not yet recruiting

Oldenburg, Germany, 26133

Sponsors and Collaborators

LEO Pharma

Investigators

• Study Director: Medical Expert; LEO Pharma

More Information

• Responsible Party: LEO Pharma
• ClinicalTrials.gov Identifier: NCT03958955 History of Changes
• Other Study ID Numbers: EXP-1373; 2018-003615-22 ( EudraCT Number )
• First Posted: May 22, 2019
• Last Update Posted: July 11, 2019
• Last Verified: June 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

De-identified 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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• Time Frame: Data is available to request after approval of the studied indication.
• URL: http://www.leo-pharma.com/Home/Research-and-Development/Clinical-trial-disclosure/Access-to-patient-level-data.aspx

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lupus Erythematosus, Systemic; Lupus Erythematosus, Discoid; Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Lupus Erythematosus, Cutaneous; Skin Diseases