Back to resultsTralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis (ECZTRA 8)
Primary Purpose
Atopic Dermatitis
Status
Completed
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
Tralokinumab
Placebo
Topical corticosteroids (TCS)
Sponsored by
About this trial
This is an interventional treatment trial for Atopic Dermatitis
Eligibility Criteria
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.
Sites / Locations
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
- LEO Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Tralokinumab+TCS
Placebo+TCS
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
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.
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.
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'.
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.
At Least 50% Reduction in EASI (EASI50) 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.
Percentage Change in EASI Score From Baseline 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
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'.
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').
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.
Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject
Number of events divided by patient years of exposure (= rate).
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04587453
Brief Title
Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis
Acronym
ECZTRA 8
Official Title
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
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
October 27, 2020 (Actual)
Primary Completion Date
July 6, 2021 (Actual)
Study Completion Date
July 15, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
LEO Pharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Atopic Dermatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Masking Description
Neither the trial participant nor any of the investigator or LEO pharma staff who are involved in the treatment or clinical evaluation and monitoring of the participants will be aware of the treatment received. The packaging and labelling of the investigational medicinal product (IMP) will contain no evidence of their identity. Since tralokinumab and placebo are visually distinct and not matched for viscosity, IMP will be handled and administered by a qualified, unblinded healthcare professional at the site who will not be involved in the management of trial participants and who will not perform any of the assessments.
Allocation
Randomized
Enrollment
106 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tralokinumab+TCS
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo+TCS
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Tralokinumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo contains the same excipients in the same concentration only lacking tralokinumab.
Intervention Type
Other
Intervention Name(s)
Topical corticosteroids (TCS)
Intervention Description
TCS administered as needed.
Primary Outcome Measure Information:
Title
Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
Description
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
Title
At Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16
Description
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 Outcome Measure Information:
Title
Change in Scoring Atopic Dermatitis (SCORAD) Total Score From Baseline to Week 16
Description
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
Title
Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16.
Description
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
Title
Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) Score (Weekly Average) of at Least 4 From Baseline to Week 16
Description
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
Title
At Least 90% Reduction in EASI (EASI90) at Week 16
Description
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
Title
At Least 50% Reduction in EASI (EASI50) at Week 16
Description
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
Title
Percentage Change in EASI Score From Baseline to Week 16
Description
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
Title
Change in Worst Daily Pruritus NRS Score (Weekly Average) From Baseline to Week 16
Description
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
Title
Change in Eczema-related Sleep NRS Score (Weekly Average) From Baseline to Week 16
Description
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
Title
Change in Patient-Oriented Eczema Measure (POEM) Score Form Baseline to Week 16
Description
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
Title
Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject
Description
Number of events divided by patient years of exposure (= rate).
Time Frame
Week 0 to Week 16
Title
Number of Subjects With Presence of Treatment-emergent Anti-drug Antibodies (ADA) From Baseline to Week 16
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Expert
Organizational Affiliation
LEO Pharma
Official's Role
Study Director
Facility Information:
Facility Name
LEO Investigational Site
City
Nagoya-shi
State/Province
Aichi
ZIP/Postal Code
457-8510
Country
Japan
Facility Name
LEO Investigational Site
City
Ichikawa-city
State/Province
Chiba
ZIP/Postal Code
272-0143
Country
Japan
Facility Name
LEO Investigational Site
City
Ichikawa-shi
State/Province
Chiba
ZIP/Postal Code
272-0033
Country
Japan
Facility Name
LEO Investigational Site
City
Chikushino-city
State/Province
Fukuoka
ZIP/Postal Code
818-0083
Country
Japan
Facility Name
LEO Investigational Site
City
Asahikawa
State/Province
Hokkaido
ZIP/Postal Code
070-8610
Country
Japan
Facility Name
LEO Investigational Site
City
Chuo-Ku-Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-0063
Country
Japan
Facility Name
LEO Investigational Site
City
Obihiro-shi
State/Province
Hokkaido
ZIP/Postal Code
080-0013
Country
Japan
Facility Name
LEO Investigational Site
City
Sapporo-shi
State/Province
Hokkaido
ZIP/Postal Code
063-0812
Country
Japan
Facility Name
LEO Investigational Site
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-0807
Country
Japan
Facility Name
LEO Investigational Site
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8186
Country
Japan
Facility Name
LEO Investigational Site
City
Nonoichi
State/Province
Ishikawa
ZIP/Postal Code
921-8801
Country
Japan
Facility Name
LEO Investigational Site
City
Kagoshima-shi
State/Province
Kagoshima
ZIP/Postal Code
890-0063
Country
Japan
Facility Name
LEO Investigational Site
City
Kawasaki-shi
State/Province
Kanagawa
ZIP/Postal Code
211-0063
Country
Japan
Facility Name
LEO Investigational Site
City
Yokohama-city
State/Province
Kanagawa
ZIP/Postal Code
221-0825
Country
Japan
Facility Name
LEO Investigational Site
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
220-6208
Country
Japan
Facility Name
LEO Investigational Site
City
Kamigyo-ku
State/Province
Kyoto
ZIP/Postal Code
602-8566
Country
Japan
Facility Name
LEO Investigational Site
City
Tokyo
State/Province
Minato
ZIP/Postal Code
108-0014
Country
Japan
Facility Name
LEO Investigational Site
City
Osaka-shi
State/Province
Osaka
ZIP/Postal Code
532-0003
Country
Japan
Facility Name
LEO Investigational Site
City
Sakai-shi
State/Province
Osaka
ZIP/Postal Code
593-8324
Country
Japan
Facility Name
LEO Investigational Site
City
Toyonaka-shi
State/Province
Osaka
ZIP/Postal Code
560-0085
Country
Japan
Facility Name
LEO Investigational Site
City
Koto-ku
State/Province
Tokyo
ZIP/Postal Code
136-0074
Country
Japan
Facility Name
LEO Investigational Site
City
Setagaya
State/Province
Tokyo
ZIP/Postal Code
158-0097
Country
Japan
Facility Name
LEO Investigational Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
160-0023
Country
Japan
Facility Name
LEO Investigational Site
City
Shinjuku-ku
State/Province
Tokyo
ZIP/Postal Code
169-0075
Country
Japan
Facility Name
LEO Investigational Site
City
Fukuoka
ZIP/Postal Code
814-0171
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified IPD can be made available to researchers in a closed environment for a specified period of time.
IPD Sharing Time Frame
Data is available to request after results of the trial are available on leopharmatrials.com
IPD Sharing Access Criteria
Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.
IPD Sharing URL
http://leopharmatrials.com/for-professionals
Learn more about this trial
Tralokinumab in Combination With Topical Corticosteroids in Japanese Subjects With Moderate-to-severe Atopic Dermatitis
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