Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis

Overview

Primary objective:

To evaluate the efficacy of tralokinumab in combination with topical corticosteroids (TCS) compared with placebo in combination with TCS in treating moderate-to-severe atopic dermatitis (AD).

Secondary objectives:

To evaluate the efficacy of tralokinumab in combination with TCS on severity and extent of AD, itch, health-related quality of life, and health care resource utilisation compared with placebo in combination with TCS.

To assess the safety of tralokinumab in combination with TCS when used to treat moderate-to-severe AD for 16 weeks.

Full Title of Study: “A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis Who Are Candidates for Systemic Therapy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: August 2021

Interventions

  • Drug: Tralokinumab
    • Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 subclass that specifically binds to human interleukin-13 (IL-13) and blocks the interaction with IL-13 receptors. It is presented as a liquid formulation for subcutaneous administration.
  • Drug: Placebo
    • Placebo contains the same excipients in the same concentration only lacking tralokinumab.
  • Other: Topical corticosteroids (TCS)
    • TCS administered as needed.

Arms, Groups and Cohorts

  • Experimental: Tralokinumab+TCS
    • Week 0 to Week 16: Tralokinumab will be given as subcutaneous injections. Participants will receive tralokinumab loading dose on Day 0 followed by multiple tralokinumab injections. The last administration will occur at Week 14. Topical corticosteroids (TCS) will be administered as needed.
  • Placebo Comparator: Placebo+TCS
    • Week 0 to Week 16: Placebo will be given as subcutaneous injections. Participants will receive placebo loading dose on Day 0 followed by multiple placebo injections. The last administration will occur at Week 14. Topical corticosteroids (TCS) will be administered as needed.

Clinical Trial Outcome Measures

Primary Measures

  • Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 16
    • Time Frame: Week 16
    • IGA is an instrument used in clinical trials to rate the severity of the participant’s global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
  • At least 75% reduction in Eczema Area and Severity Index (EASI75) at Week 16
    • Time Frame: Week 16
    • Eczema Area and Severity Index (EASI) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition.

Secondary Measures

  • Change in Scoring Atopic Dermatitis (SCORAD) total score from baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.
  • Change in Dermatology Life Quality Index (DLQI) score from baseline to Week 16.
    • Time Frame: Week 0 to Week 16
    • DLQI consists of 10 items addressing the participant’s perception of the impact of their skin disease on different aspects of their health-related quality of life over the past week, such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0=not at all ⁄ not relevant; 1=a little; 2=a lot; 3=very much). The total score is the sum of the 10 items (ranging from 0 to 30), with higher scores indicating poorer health-related quality of life.
  • Reduction of Worst Daily Pruritus numeric rating scale (NRS) score (weekly average) of at least 4 from baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • Participants assess their worst itch severity over the past 24 hours using an 11-point NRS (Worst Daily Pruritus NRS) with 0 indicating ‘no itch’ and 10 indicating ‘worst itch imaginable’.
  • At least 90% reduction in EASI (EASI90) at Week 16
    • Time Frame: Week 16
    • EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition.
  • At least 50% reduction in EASI (EASI50) at Week 16
    • Time Frame: Week 16
    • EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition.
  • Percentage change in EASI score from baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. EASI is a composite index with scores ranging from 0 to 72, where higher values indicate a more severe or more extensive condition.
  • Change in Worst Daily Pruritus NRS score (weekly average) from baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • Participants assess their worst itch severity over the past 24 hours using an 11-point NRS (Worst Daily Pruritus NRS) with 0 indicating ‘no itch’ and 10 indicating ‘worst itch imaginable’.
  • Change in Eczema-related Sleep NRS score (weekly average) from baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • Participants rate how much their eczema interfered with their sleep the last night using an 11-point NRS (0 indicating that it ‘did not interfere’ and 10 indicating that it ‘completely interfered’).
  • Change in Patient-Oriented Eczema Measure (POEM) score form baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • POEM consists of 7 items, each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness). Participants score how often they have experienced each symptom over the previous week, using a 5-point categorical response scale (0=no days; 1=1 to 2 days; 2=3 to 4 days; 3=5 to 6 days; 4=every day). The total score is the sum of the 7 items (ranging from 0 to 28) and reflects disease-related morbidity; higher scores indicate more severe disease.
  • Number of treatment-emergent adverse events from baseline to Week 16 per subject
    • Time Frame: Week 0 to Week 16
  • Presence of treatment-emergent anti-drug antibodies from baseline to Week 16
    • Time Frame: Week 0 to Week 16
    • Anti-tralokinumab antibody levels will be analysed using a validated bioanalytical method.

Participating in This Clinical Trial

Key inclusion criteria:

  • Japanese subject aged 18 years and above.
  • Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD.
  • History of AD for 1 year or more.
  • A recent history (within 1 year before screening) of inadequate response to treatment with topical medication.
  • AD involvement of 10% or more body surface area at screening and at baseline according to component A of SCORAD.
  • Applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation.

Key exclusion criteria:

  • Subjects for whom TCS are medically inadvisable e.g. due to important side effects or safety risks in the opinion of the investigator.
  • Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment.
  • Use of tanning beds or phototherapy within 6 weeks prior to randomisation.
  • Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroids within 4 weeks prior to randomisation.
  • Treatment with TCS, topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors, or topical Janus kinase inhibitors within 2 weeks prior to randomisation.
  • Receipt of any marketed biological therapy (i.e. immunoglobulin, anti-immunoglobulin E) including dupilumab or investigational biologic agents 3 to 6 months prior to randomisation.
  • Active skin infections within 1 week prior to randomisation.
  • Clinically significant infection within 4 weeks prior to randomisation.
  • A helminth parasitic infection within 6 months prior to the date informed consent is obtained.
  • Tuberculosis requiring treatment within the 12 months prior to screening.
  • Known primary immunodeficiency disorder.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • LEO Pharma
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Expert, Study Director, LEO Pharma
  • Overall Contact(s)
    • Clinical Disclosure, (+1) 877-577-1168, disclosure@leo-pharma.com

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