Phase 2b Dose-ranging Trial to Evaluate Delgocitinib Cream 1, 3, 8, and 20 mg/g Compared to Delgocitinib Cream Vehicle Over a 16-week Treatment Period in Adult Subjects With Chronic Hand Eczema

• ClinicalTrials.gov Identifier: NCT03683719
• Recruitment Status: Completed
• First Posted: September 25, 2018
• Results First Posted: April 19, 2021
• Last Update Posted: April 19, 2021
• Sponsor: LEO Pharma
• Information provided by (Responsible Party): LEO Pharma

Tracking Information

• First Submitted Date: September 21, 2018
• First Posted Date: September 25, 2018
• Results First Submitted Date: March 23, 2021
• Results First Posted Date: April 19, 2021
• Last Update Posted Date: April 19, 2021
• Actual Study Start Date: November 28, 2018
• Actual Primary Completion Date: March 6, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 15, 2021)

Investigator's Global Assessment for Chronic Hand Eczema (IGA-CHE) Score of 0 (Clear) or 1 (Almost Clear) With at Least a 2-step Improvement (IGA-CHE Treatment Success) From Baseline to Week 16. [ Time Frame: Week 0 to Week 16. ]

IGA-CHE is an instrument used in clinical trials to rate the severity of subject's global disease stage 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 delgocitinib cream vehicle.

Original Primary Outcome Measures (submitted: September 21, 2018)

Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) with at least a 2-step improvement (IGA 0/1) from baseline to Week 16. [ Time Frame: Week 0 to Week 16. ]

IGA is an instrument used in clinical trials to rate the severity of subject's global disease stage and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).

Current Secondary Outcome Measures (submitted: April 15, 2021)

• Change in Hand Eczema Severity Index (HECSI) From Baseline to Week 16. [ Time Frame: Week 0 to Week 16. ]
  HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The highest possible HECSI score is 360. The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose selection. A mixed model for repeated measurements (MMRM) analysis was used to determine the difference in the continuous endpoint between the active delgocitinib cream doses and delgocitinib cream vehicle.
• Time to IGA-CHE Treatment Success. [ Time Frame: Week 0 to Week 16. ]
  Time to IGA-CHE treatment success response is defined as the time from baseline to first assessment of an IGA-CHE score of 0 (clear) or 1 (almost clear) with at least a 2-step improvement.

Original Secondary Outcome Measures (submitted: September 21, 2018)

• Change in Hand Eczema Severity Index (HECSI) From Baseline to Week 16. [ Time Frame: Week 0 to Week 16. ]
  HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area).
• Time to IGA 0/1. [ Time Frame: Week 0 to Week 16. ]
  Time to IGA 0/1 response is defined as the time from baseline to first assessment of an IGA 0/1.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Phase 2b Dose-ranging Trial to Evaluate Delgocitinib Cream 1, 3, 8, and 20 mg/g Compared to Delgocitinib Cream Vehicle Over a 16-week Treatment Period in Adult Subjects With Chronic Hand Eczema
• Official Title: A Phase 2b, Double-blind, Randomised, 5-arm, Vehicle-controlled, Dose-ranging Trial to Evaluate the Efficacy and Safety of Twice Daily Topical Application of Delgocitinib Cream 1, 3, 8, and 20 mg/g for 16 Weeks in Adult Subjects With Mild to Severe Chronic Hand Eczema
• Brief Summary: The purpose of this research trial was to test different strengths of a new trial medication, delgocitinib cream 1, 3, 8, and 20 mg/g, and to investigate how treatment with delgocitinib cream affects chronic hand eczema. This was judged by a range of assessments that rate the severity and extent of chronic hand eczema and its symptoms, as well as general health status and quality of life.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Chronic Hand Eczema

Intervention

• Drug: Delgocitinib cream
  Cream for topical application.
  Other Name: LEO 124249 cream
• 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

Study Arms

• Experimental: Delgocitinib cream 1 mg/g
  Delgocitinib cream applied twice daily for 16 weeks.
  Intervention: Drug: Delgocitinib cream
• Experimental: Delgocitinib cream 3 mg/g
  Delgocitinib cream applied twice daily for 16 weeks.
  Intervention: Drug: Delgocitinib cream
• Experimental: Delgocitinib cream 8 mg/g
  Delgocitinib cream applied twice daily for 16 weeks.
  Intervention: Drug: Delgocitinib cream
• Experimental: Delgocitinib cream 20 mg/g
  Delgocitinib cream applied twice daily for 16 weeks.
  Intervention: Drug: Delgocitinib cream
• Placebo Comparator: Delgocitinib cream vehicle
  Delgocitinib cream vehicle applied twice daily for 16 weeks.
  Intervention: Drug: Delgocitinib cream vehicle

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 8, 2020): 258
• Original Estimated Enrollment (submitted: September 21, 2018): 250
• Actual Study Completion Date: April 20, 2020
• Actual Primary Completion Date: March 6, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Age 18 years or above.
• Diagnosis of chronic hand eczema defined as hand eczema, which has persisted for more than 3 months or returned twice or more within the last 12 months.
• Disease severity graded as mild to severe according to IGA (i.e., IGA ≥2).
• Recent history (within 1 year before the screening visit) of inadequate response to topical corticosteroid treatment or topical corticosteroid treatment being medically inadvisable.
• Diagnostic patch testing performed within 3 years prior to the screening visit.

Key Exclusion Criteria:

• Concurrent skin diseases on the hands e.g tinnea manuum.
• Active atopic dermatitis in regions other than the hands or psoriasis requiring medical treatment.
• Clinically significant infection (e.g., impetiginised hand eczema) on the hands.
• Systemic treatment with immunosuppressive drugs, immunomodulating drugs, retinoids, or corticosteroids within 4 weeks prior to baseline.
• Psoralen ultraviolet A (PUVA) or ultraviolet B (UVB) therapy on the hands within 4 weeks prior to baseline.
• Receipt of live attenuated vaccines 4 weeks prior to baseline.
• Cutaneously applied treatment with immunomodulators (e.g., phosphodiesterase-4 (PDE-4) inhibitors, pimecrolimus, tacrolimus) or topical corticosteroids on the hands within 2 weeks prior to baseline.
• Use of systemic antibiotics or cutaneously applied antibiotics on the hands within 2 weeks prior to baseline.
• Change in systemic antihistamine therapy within 2 weeks prior to baseline i.e., subjects must not start antihistamine treatment or change the current dosage regime within 2 weeks prior to baseline.
• Other cutaneously applied therapy on the hands (except for the use of subject's own emollients) within 1 week prior to baseline.
• Cutaneously applied treatments in regions other than the hands, which could interfere with clinical trial evaluations or pose a safety concern within 1 week prior to baseline.
• Receipt of any marketed or investigational biologic agents within 6 months or 5 half-lives prior to baseline or until cells count returns to normal, whichever is longer.
• Clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to baseline.
• Tuberculosis requiring treatment within 12 months prior to screening and/or subjects with a positive blood test for tuberculosis at screening.
• History of any known primary immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at screening, or the subject taking antiretroviral medications.
• Any disorder which is not stable and in the investigator's opinion could affect the safety of the subject, influence the findings of the trial, or impede the subject's ability to complete the trial.
• Positive hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (anti-HCV) serology at screening. Subjects with positive HBsAb may be randomised provided they are hepatitis B vaccinated and have negative HBsAg and HBcAb.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Germany, United States

Administrative Information

• NCT Number: NCT03683719
• Other Study ID Numbers: LP0133-1273
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• URL: https://www.leopharmatrials.com/For-professionals

• Responsible Party: LEO Pharma
• Study Sponsor: LEO Pharma
• Collaborators: Not Provided

Investigators

• Study Director: Medical Expert; LEO Pharma

• PRS Account: LEO Pharma
• Verification Date: April 2021