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Trial record 2 of 8 for:    ECZTRA

Tralokinumab Monotherapy for Moderate to Severe Atopic Dermatitis - ECZTRA 2 (ECZema TRAlokinumab Trial no. 2) (ECZTRA 2)

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ClinicalTrials.gov Identifier: NCT03160885
Recruitment Status : Completed
First Posted : May 19, 2017
Results First Posted : August 24, 2020
Last Update Posted : August 24, 2020
Sponsor:
Information provided by (Responsible Party):
LEO Pharma

Brief Summary:

Primary objective:

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

Secondary objectives:

To evaluate the efficacy of tralokinumab on severity and extent of AD, itch, and health related quality of life compared with placebo.

Maintenance objective:

To evaluate maintenance of effect with continued tralokinumab dosing up to 52 weeks compared to placebo for subjects achieving clinical response at Week 16.


Condition or disease Intervention/treatment Phase
Atopic Dermatitis Drug: Tralokinumab Drug: Placebo Phase 3

Detailed Description:

Subjects found eligible following the screening period were randomized 3:1 to initial treatment with tralokinumab 300 mg every 2 weeks (Q2W) or placebo. Randomization was stratified by region (Asia, Australia, Europe, and North America) and disease severity (Investigator's Global Assessment [IGA] 3 or 4).

Subjects achieving a clinical response at Week 16 (defined as IGA of 0 or 1 on a 5-point scale ranging from 0 [clear] to 4 [severe], or at least 75% reduction in Eczema Area and Severity Index [EASI] score from baseline [EASI75]) continued into maintenance treatment that continued until Week 52.

Subjects randomized to tralokinumab in the initial treatment period and who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) were re-randomized 2:2:1 to one of the following Q2W maintenance regimens stratified by region (Asia, Australia, Europe, and North America) and IGA response at Week 16 (IGA 0/1 or IGA >1):

  • Tralokinumab 300 mg Q2W.
  • Tralokinumab 300 mg Q4W (alternating dose administrations tralokinumab 300 mg and placebo).
  • Placebo.

Subjects randomized to placebo in the initial treatment period who achieved a clinical response at Week 16 (defined by IGA 0 or 1, or EASI75) continued to receive placebo Q2W in the maintenance treatment period.

Subjects not achieving a clinical response at Week 16 as well as those who met the criteria listed below during maintenance treatment were transferred to open-label tralokinumab 300 mg Q2W treatment with optional use of topical corticosteroid (TCS) up to Week 52.

Transfer to open-label treatment during maintenance:

Subjects with IGA=0 at Week 16: IGA of at least 2 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects with IGA=1 at Week 16: IGA of at least 3 and not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects with IGA >1 at Week 16: not achieved EASI75 over at least a 4-week period (i.e. over 3 consecutive visits).

Subjects transferring to open-label treatment had the option to self-administer tralokinumab in their home after adequate training (at 3 dosing visits in the open-label period after additional consent has been obtained) by site staff at the investigator's discretion.

After completion of the maintenance treatment period (or open-label treatment), all subjects, except for those who entered the open-label long-term extension trial, continued in a 14-week off-treatment follow-up period for the assessment of safety and anti-drug antibody (ADA).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 794 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Neither the subject nor any of the investigator or LEO staff who are involved in the treatment or clinical evaluation and monitoring of the subjects will be aware of the treatment received. The packaging and labelling of the investigational medicinal products (IMPs) 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 (HCP) at the site who will not be involved in the management of trial subjects and who will not perform any of the assessments.

Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Placebo-controlled, Phase 3 Trial to Evaluate the Efficacy and Safety of Tralokinumab Monotherapy in Subjects With Moderate to Severe Atopic Dermatitis Who Are Candidates for Systemic Therapy
Actual Study Start Date : June 12, 2017
Actual Primary Completion Date : September 4, 2018
Actual Study Completion Date : August 14, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Eczema

Arm Intervention/treatment
Experimental: Initial treatment period - Tralokinumab Q2W

Week 0 to Week 16

Two subcutaneous (SC) injections of tralokinumab as a loading dose on Day 0, followed by a SC injection of tralokinumab Q2W regimen for 16 weeks

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration

Placebo Comparator: Initial treatment period - Placebo

Week 0 to Week 16 (Initial treatment period):

Two subcutaneous (SC) injections of placebo as a loading dose on Day 0 followed by a SC injection of placebo Q2W regimen for 16 weeks

Drug: Placebo
Placebo contains the same excipients, in the same concentration only lacking tralokinumab

Experimental: Maintenance treatment period - Tralokinumab Q2W

Week 16 to Week 52

Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q2W for 36 weeks

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration

Experimental: Maintenance treatment period - Tralokinumab Q4W

Week 16 to Week 52

Tralokinumab responders from the initial treatment period re-randomised at Week 16 and administered tralokinumab maintenance subcutaneous injection regimen Q4W for 36 weeks.

Participants in this group receive alternating doses of tralokinumab SC injection and placebo SC injection every 2 weeks

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration

Drug: Placebo
Placebo contains the same excipients, in the same concentration only lacking tralokinumab

Placebo Comparator: Maintenance treatment period - Placebo

Week 16 to Week 52

Tralokinumab responders from initial treatment period randomised at Week 16 and administered placebo subcutaneous maintenance injection for 36 weeks

Drug: Placebo
Placebo contains the same excipients, in the same concentration only lacking tralokinumab

Placebo Comparator: Maintenance treatment period - Placebo (tralokinumab naive)

Week 16 to Week 52

Placebo responders from the initial treatment period re-assigned at Week 16 and administered placebo maintenance subcutaneous injection regimen Q2W for 36 weeks

Drug: Placebo
Placebo contains the same excipients, in the same concentration only lacking tralokinumab

Experimental: Open-label treatment - Tralokinumab 300 mg Q2W + optional TCS

Week 16 to Week 52

Subjects receiving initial treatment with tralokinumab Q2W or placebo Q2W assigned to open-label treatment at Week 16 and administered tralokinumab subcutaneous (SC) injection + optional TCS* regimen Q2W

OR

Subjects receiving maintenance treatment with tralokinumab Q2W/Q4W or placebo assigned to open-label treatment after Week 16 and administered tralokinumab SC injection + optional TCS regimen Q2W

• TCS = topical corticosteroids

Drug: Tralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration




Primary Outcome Measures :
  1. Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16. [ Time Frame: At Week 16 ]
    The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).

  2. Subjects Achieving at Least 75% Reduction in Eczema Area and Severity Index [EASI]. [ Time Frame: At Week 16 ]
    The 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 and/or more extensive condition.


Secondary Outcome Measures :
  1. Reduction of Worst Daily Pruritus Numeric Rating Scale (Weekly Average) of at Least 4 From Baseline to Week 16. [ Time Frame: Week 0 to Week 16 ]
    Subjects will 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'.

  2. Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16. [ Time Frame: Week 0 to Week 16 ]
    The 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.

  3. Change in Dermatology Life Quality Index (DLQI) Score From Baseline to Week 16. [ Time Frame: Week 0 to Week 16 ]
    The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their quality of life (QoL) over the last 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 (0 to 30); a high score is indicative of a poor QoL.

  4. Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA of 0/1 at Week 16 [ Time Frame: At Week 52 ]
    The IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).

  5. Subjects With at Least 75% Reduction in Eczema Area and Severity Index [EASI] at Week 52 Among Subjects With EASI75 at Week 16 [ Time Frame: At Week 52 ]
    The 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 and/or more extensive condition.

  6. Safety and Tolerability: Adverse Event (AE) /Serious Adverse Event (SAE) Frequency [ Time Frame: Week 0 to Week 16 ]
    Overall summary of AEs and SAEs during the Initial treatment period is presented. For list of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.

  7. Frequency of Anti-drug Antibodies [ Time Frame: Week 0 to Week 16 ]
    Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method

  8. Subjects Achieving at Least 50% Reduction in Eczema Area and Severity Index [EASI] at Week 16 [ Time Frame: At Week 16 ]
    The 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 and/or more extensive condition.

  9. Subjects Achieving at Least 90% Reduction in Eczema Area and Severity Index [EASI] at Week 16. [ Time Frame: At Week 16 ]
    The 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 and/or more extensive condition.

  10. Change From Baseline to Week 16 in Eczema Area and Severity Index [EASI] Score [ Time Frame: At Week 16 ]
    The 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 and/or more extensive condition.

  11. Subjects Achieving at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16. [ Time Frame: At Week 16 ]
    The 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.

  12. Subjects Achieving at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD) at Week 16. [ Time Frame: At Week 16 ]
    The 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.

  13. Change From Baseline to Week 16 in Worst Daily Pruritus NRS (Weekly Average). [ Time Frame: Baseline to Week 16 ]
    Subjects will 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'

  14. Reduction of Worst Daily Pruritus NRS (Weekly Average) ≥3 From Baseline to Week 16. [ Time Frame: Baseline to Week 16 ]
    Subjects will 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'.

  15. Reduction From Baseline to Week 16 of Dermatology Life Quality Index (DLQI) of ≥4 Points Among Subjects With Baseline DLQI ≥4. [ Time Frame: Baseline to Week 16 ]
    The DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their QoL over the last 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 (0 to 30); a high score is indicative of a poor QoL.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 and above.
  • Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD.
  • Diagnosis of AD for ≥1 year.
  • Subjects who have a recent history of inadequate response to treatment with topical medications or for whom topical treatments are otherwise medically inadvisable.
  • AD involvement of ≥10% body surface area at screening and baseline.
  • Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomization

Exclusion Criteria:

  • Active dermatologic conditions that may confound the diagnosis of AD.
  • Use of tanning beds or phototherapy within 6 weeks prior to randomisation.
  • Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to randomisation.
  • Treatment with TCS and/or topical calcineurin inhibitor (TCI) within 2 weeks prior to randomisation.
  • Active skin infection 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.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.0 times the upper limit of normal (ULN) at screening.
  • Positive hepatitis B surface antigen, hepatitis B surface antibody, hepatitis B core antibody or hepatitis C virus antibody serology at screening.
  • History of anaphylaxis following any biologic therapy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03160885


Locations
Show Show 115 study locations
Sponsors and Collaborators
LEO Pharma
Investigators
Layout table for investigator information
Principal Investigator: Eric Simpson, MD, MCR Department of Dermatology, Oregon Health and Science University
  Study Documents (Full-Text)

Documents provided by LEO Pharma:
Statistical Analysis Plan  [PDF] June 14, 2019
Study Protocol  [PDF] August 14, 2018

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: LEO Pharma
ClinicalTrials.gov Identifier: NCT03160885    
Other Study ID Numbers: LP0162-1326
2016-004201-13 ( EudraCT Number )
First Posted: May 19, 2017    Key Record Dates
Results First Posted: August 24, 2020
Last Update Posted: August 24, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified Individual Participant Data can be made available to researchers in a closed environment for a specified period of time.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data are available to request after results of the trial are available on leopharmatrials.com
Access Criteria: Data-sharing is subject to approved scientifically sound research proposal and signed data-sharing agreement.
URL: http://leopharmatrials.com/for-professionals

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Dermatitis, Atopic
Dermatitis
Eczema
Skin Diseases
Skin Diseases, Genetic
Genetic Diseases, Inborn
Skin Diseases, Eczematous
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases