Dose-ranging Trial to Evaluate Delgocitinib Cream 1, 3, 8, and 20 mg/g Compared to Delgocitinib Cream Vehicle Over an 8-week Treatment Period in Adult Subjects With Atopic Dermatitis.

A Phase 2b, Double-blind, Randomised, 5-arm, Vehicle-controlled, Dose Ranging Trial to Evaluate the Efficacy and Safety of Twice Daily Topical Applications of Delgocitinib Cream 1, 3, 8, 20 mg/g for 8 Weeks in Adult Subjects With Mild to Severe Atopic Dermatitis.

This is a double-blind, multi-centre, randomised, 5-arm, vehicle-controlled, parallel-group trial. The trial is designed to establish a dose-response signal and investigate the efficacy and safety of delgocitinib cream in the treatment of adult subjects with mild to severe atopic dermatitis (AD).

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Delgocitinib cream; Drug: Delgocitinib cream vehicle

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Carlton, Australia, 3053
    • LEO Pharma Investigational Site
  • Darlinghurst, Australia, 2010
    • LEO Pharma Investigational Site
  • East Melbourne, Australia, 3002
    • LEO Pharma Investigational Site
  • Hectorville, Australia, 5073
    • LEO Pharma Investigational Site
  • Kogarah, Australia, 2217
    • LEO Pharma Investigational Site 1
  • Kogarah, Australia, 2217
    • LEO Pharma Investigational Site
  • Woolloongabba, Australia, 4102
    • LEO Pharma Investigational Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • LEO Pharma Investigational Site
    • Edmonton, Alberta, Canada, T5K 1X3
      • LEO Pharma Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3R 6A7
      • LEO Pharma Investigational Site
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • LEO Pharma Investigational Site
  • New Brunswick
    • Fredericton, New Brunswick, Canada, E3B 1G9
      • LEO Pharma Investigational Site
  • Ontaria
    • Mississauga, Ontaria, Canada, L5H 1G9
      • LEO Pharma Investigational Site
  • Ontario
    • Barrie, Ontario, Canada, L4M 7G1
      • LEO Pharma Investigational Site
    • Markham, Ontario, Canada, L3P 1X2
      • LEO Pharma Investigational Site
    • Peterborough, Ontario, Canada, K9J 5K2
      • LEO Pharma Investigational Site
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • LEO Pharma Investigational Site
    • Toronto, Ontario, Canada, M2M 4J5
      • LEO Pharma Investigational Site
    • Toronto, Ontario, Canada, M2W 2N2
      • LEO Pharma Investigational Site
    • Toronto, Ontario, Canada, M3H 5Y8
      • LEO Pharma Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • LEO Pharma Investigational Site
  • California
    • Encino, California, United States, 91436
      • LEO Pharma Investigational Site
    • Los Angeles, California, United States, 90033
      • LEO Pharma Investigational Site
    • Los Angeles, California, United States, 90045
      • LEO Pharma Investigational Site
    • Rolling Hills Estates, California, United States, 90274-7604
      • LEO Pharma Investigational Site
    • Santa Ana, California, United States, 92701
      • LEO Pharma Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • LEO Pharma Investigational Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • LEO Pharma Investigational Site
  • New York
    • New York, New York, United States, 10019
      • LEO Pharma Investigational Site
  • North Carolina
    • High Point, North Carolina, United States, 27262
      • LEO Pharma Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Age 18 years and above.
• Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD.
• History of AD for ≥1 year.
• AD involvement of 5-50% treatable body surface area at screening and at baseline (excluding scalp).
• Disease severity graded as mild to severe according to vIGA-AD (i.e. vIGA-AD ≥2) at screening and baseline.

Key Exclusion Criteria:

• AD lesion(s) on scalp at screening and/or baseline.
• Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, rosacea, urticaria, or psoriasis.
• Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD.
• Use of tanning beds or phototherapy within 4 weeks prior to baseline.
• Systemic treatment with immunosuppressive/modulating drugs or corticosteroids within 4 weeks prior to baseline or 3 or more bleach baths any week within 4 weeks prior to baseline.
• Treatment with topical corticosteroids, topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors, or oral antibiotics within 2 weeks prior to baseline.
• Change in systemic antihistamine therapy within 2 weeks prior to baseline i.e. the subjects must not start antihistamine treatment or change the current dosage regime within 2 weeks prior to baseline.
• Receipt of live attenuated vaccines within 4 weeks prior to baseline.
• Treatment with any marketed or investigational biologic agents within 6 months or 5 half-lives prior to baseline, or until cell counts return to normal, whichever is longer.
• History of any active skin infection within 1 week prior to baseline.
• Clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to baseline.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Delgocitinib cream 1 mg/g; Delgocitinib cream applied twice daily for 8 weeks	Drug: Delgocitinib cream; Cream for topical application; Other Names: LEO 124249 cream
Experimental: Delgocitinib cream 3 mg/g; Delgocitinib cream applied twice daily for 8 weeks	Drug: Delgocitinib cream; Cream for topical application; Other Names: LEO 124249 cream
Experimental: Delgocitinib cream 8 mg/g; Delgocitinib cream applied twice daily for 8 weeks	Drug: Delgocitinib cream; Cream for topical application; Other Names: LEO 124249 cream
Experimental: Delgocitinib cream 20 mg/g; Delgocitinib cream applied twice daily for 8 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 8 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
Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score.	EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe or more extensive condition. The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose selection. Mixed Model for Repeated Measurements (MMRM) analysis was used to determine the difference in the continuous endpoint between the active delgocitinib doses and delgocitinib cream vehicle.	Week 0 to Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8.	vIGA-AD is an instrument used in clinical trials to assess the subject's global disease severity and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose-selection. Cochran-Mantel-Haenszel analysis was used to determine the difference in response rates between the active delgocitinib cream doses and the delgocitinib cream vehicle.	Week 0 to Week 8
EASI75 at Week 8	EASI75 is defined as at least 75% reduction in EASI from baseline.	Week 0 to Week 8
Time to vIGA-AD TS	The time to vIGA-AD TS response is defined as the time from baseline to first assessment of a vIGA-AD score of 0 (Clear) or 1 (Almost Clear) with ≥2-step improvement	Week 0 to Week 8

Collaborators and Investigators

• Sponsor: LEO Pharma

Study record dates

Study Major Dates

• Study Start (Actual): December 28, 2018
• Primary Completion (Actual): May 19, 2020
• Study Completion (Actual): May 19, 2020

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: October 30, 2018
• First Posted (Actual): October 31, 2018

Study Record Updates

• Last Update Posted (Actual): July 8, 2021
• Last Update Submitted That Met QC Criteria: July 6, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: LP0133-1275

Plan for Individual participant data (IPD)

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