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

LEO Pharma106 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

106

Conditions

Atopic Dermatitis

Interventions

Tralokinumab

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (25)

LEO Investigational Site

Nagoya, Aichi-ken, Japan

LEO Investigational Site

Ichikawa, Chiba, Japan

LEO Investigational Site

Ichikawa-shi, Chiba, Japan

LEO Investigational Site

Chikushino-shi, Fukuoka, Japan

LEO Investigational Site

Asahikawa, Hokkaido, Japan

LEO Investigational Site

Chuo-Ku-Sapporo, Hokkaido, Japan

LEO Investigational Site

Obihiro-shi, Hokkaido, Japan

LEO Investigational Site

Sapporo, Hokkaido, Japan

LEO Investigational Site

Sapporo, Hokkaido, Japan

LEO Investigational Site

Nishinomiya, Hyōgo, Japan

...and 15 more locations

Outcomes

Primary Outcomes

Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at 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).

Time frame: Week 16

At Least 75% Reduction in Eczema Area and Severity Index (EASI75) at 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.

Time frame: Week 0 to Week 16

Secondary Outcomes

Change in Scoring Atopic Dermatitis (SCORAD) Total Score From Baseline to Week 16

SCORAD is a validated tool to evaluate the AD disease based on 3 components: * A) The extent of AD lesions. Assessed as percentage of each defined body area and reported as sum of all areas (max score = 100%). * B) The severity of AD lesions. The intensity of 6 specific symptoms on a representative area was assessed using the scale: 0 = none/absent, 1 = mild, 2 = moderate, 3 = severe (max score = 18). * C) Subjective symptoms. The itch and sleeplessness over the last 3 days/nights was recorded for each symptom by the subject on a VAS scale: 0 = no itch or trouble sleeping, 10 = unbearable itch or a lot of trouble sleeping (max score = 20). The SCORAD was calculated as: A/5+7B/2+C. The maximum total score is 103, with higher values indicating more severe disease.

Time frame: Week 0 to Week 16

Change in Dermatology Life Quality Index (DLQI) Score From Baseline 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.

Time frame: Week 0 to Week 16

Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) Score (Weekly Average) of at Least 4 From Baseline to Week 16

Participants assessed the itch for the past 24 hours using the Worst Daily Pruritus NRS, consisting of 11 points, with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.

Time frame: Week 0 to Week 16

At Least 90% Reduction in EASI (EASI90) at 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.

Time frame: Week 0 to Week 16

At Least 50% Reduction in EASI (EASI50) at Week 16

Time frame: Week 0 to Week 16

Percentage Change in EASI Score From Baseline to Week 16

Time frame: Week 0 to Week 16

Change in Worst Daily Pruritus NRS Score (Weekly Average) From Baseline to Week 16

Participants assessed the itch for the past 24 hours using the Worst Daily Pruritus NRS, consisting of 11 points, with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.

Time frame: Week 0 to Week 16

Change in Eczema-related Sleep NRS Score (Weekly Average) From Baseline to Week 16

Participants rated 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').

Time frame: Week 0 to Week 16

Change in Patient-Oriented Eczema Measure (POEM) Score Form Baseline 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.

Time frame: Week 0 to Week 16

Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject

Number of events divided by patient years of exposure (= rate).

Time frame: Week 0 to Week 16

Number of Subjects With Presence of Treatment-emergent Anti-drug Antibodies (ADA) From Baseline to Week 16

Anti-tralokinumab antibody levels were analyzed using a validated bioanalytical method. Positive treatment-emergent ADA was defined as ADA negative or missing at baseline, and at least one positive post-baseline ADA response. Negative treatment-emergent ADA was defined as ADA negative or missing at baseline, and all post-baseline ADA assessments negative.

Time frame: Week 0 to Week 16