Vaccine Responses in Tralokinumab-Treated Atopic Dermatitis - ECZTRA 5 (ECZema TRAlokinumab Trial No. 5) (ECZTRA 5)

• ClinicalTrials.gov Identifier: NCT03562377
• Recruitment Status: Completed
• First Posted: June 19, 2018
• Results First Posted: March 5, 2021
• Last Update Posted: March 5, 2021
• Sponsor: LEO Pharma
• Information provided by (Responsible Party): LEO Pharma

Tracking Information

• First Submitted Date: June 8, 2018
• First Posted Date: June 19, 2018
• Results First Submitted Date: January 14, 2021
• Results First Posted Date: March 5, 2021
• Last Update Posted Date: March 5, 2021
• Actual Study Start Date: July 13, 2018
• Actual Primary Completion Date: September 17, 2019 (Final data collection date for primary outcome measure)

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

• Positive Anti-tetanus Response at Week 16 [ Time Frame: Week 12 to Week 16 ]
  The antibody response to Tdap vaccine will be assessed by measuring serum anti-tetanus IgG by an immunoassay. A positive response is defined as a 3-fold IgG increase compared to Week 12 if IgG ≤1.0 IU/mL at Week 12; or IgG ≥2.5 IU/mL if IgG >1.0 IU/mL at Week 12.
• Positive Anti-meningococcal Response at Week 16 [ Time Frame: Week 12 to Week 16 ]
  The antibody response to meningococcal vaccine will be assessed by measuring serum anti-meningococcal IgG by an immunoassay. A positive response is defined as IgG ≥3.0 µg/mL with at least a 3-fold increase compared to Week 12.

Original Primary Outcome Measures (submitted: June 8, 2018)

• Positive Anti-tetanus Response at Week 16 [ Time Frame: Week 12 to Week 16 ]
  The antibody response to Tdap vaccine will be assessed by measuring serum anti-tetanus IgG by an immunoassay.
• Positive Anti-meningococcal Response at Week 16 [ Time Frame: Week 12 to Week 16 ]
  The antibody response to meningococcal vaccine will be assessed by measuring serum anti-meningococcal IgG by an immunoassay.

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

• Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 [ Time Frame: Week 0 to Week 16 ]
  The IGA is an instrument used in clinical trials to rate the severity of the subject's global atopic dermatitis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
• Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16. [ Time Frame: Week 0 to Week 16 ]
  The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis. > The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
• Number of AEs. [ Time Frame: Week 0 to Week 16 ]
  Overall summary of AEs during the treatment period is presented. For list of SAEs and frequent AEs by MedDRA system organ class (SOC) and preferred term (PT) during the entire trial period (including safety follow-up), see Adverse Events Overview section.
• Presence of Anti-drug Antibodies (ADA). [ Time Frame: Week 0 to Week 16 ]
  ADA levels were measured using a validated bioanalytical method. Data were reported in the following categories: positive (presence of ADA at baseline and/or presence of ADA at at least 1 post-baseline assessment), perishing (presence of ADA at baseline and absence of ADA at all post-baseline assessments), negative (absence of ADA at all assessments), no post-baseline ADA assessment.

Original Secondary Outcome Measures (submitted: June 8, 2018)

• Subjects with Investigator's Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) at Week 16 [ Time Frame: Week 0 to Week 16 ]
  The IGA is an instrument used in clinical trials to rate the severity of the subject's global atopic dermatitis and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
• Subjects achieving at least 75% reduction in Eczema Area and Severity Index (EASI) at Week 16. [ Time Frame: Week 0 to Week 16 ]
  The EASI is a validated measure used in clinical practice and clinical trials to assess the severity and extent of atopic dermatitis. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.

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

Descriptive Information

• Brief Title: Vaccine Responses in Tralokinumab-Treated Atopic Dermatitis - ECZTRA 5 (ECZema TRAlokinumab Trial No. 5)
• Official Title: A Randomised, Double-blind, Placebo-controlled Trial to Evaluate the Effect of Tralokinumab on Vaccine Antibody Responses in Adults With Moderate-to-severe Atopic Dermatitis Who Are Candidates for Systemic Therapy
• Brief Summary: The purpose of this trial is to test if treatment with the trial drug, tralokinumab, can affect the body's immune response to vaccines. The trial will also evaluate the efficacy of tralokinumab when it is given concomitantly with vaccines.> The trial includes a screening period of 2 to 6 weeks, a treatment period of 16 weeks (Weeks 0 to 16), and a 14-week off-treatment follow-up period for the assessment of safety (Weeks 16 to 30). Eligible subjects may transfer to an open-label, long-term trial at Week 16 or later.

Detailed Description

Subjects with atopic dermatitis (AD) will be treated with either tralokinumab or dummy treatment (placebo) for 16 weeks. All subjects will receive 2 vaccines at Week 12. The vaccines are: >

1. Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. This combination vaccine is also known as the Tdap vaccine and is used to prevent these 3 diseases.>
2. Meningococcal vaccine. This vaccine is used to prevent meningococcal diseases (infection of the brain and spinal cord) and blood poisoning.> > The primary objective of the trial is to demonstrate non-inferiority of tralokinumab versus placebo with respect to immune responses to concomitantly administered vaccines.> The secondary objective is to evaluate efficacy of tralokinumab concomitantly administered with vaccines.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

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 tralokinumab/placebo will contain no evidence of their identity.

> Since tralokinumab and placebo are visually distinct and not matched for viscosity, they will be handled and administered by a qualified, unblinded healthcare professional at the trial site who will not be involved in the management of trial subjects.

Primary Purpose: Treatment

• Condition: Atopic Dermatitis

Intervention

• 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 administration.
• Drug: Placebo
  Placebo contains the same excipients in the same concentration only lacking tralokinumab.
• Biological: Tdap vaccine
  Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. All subjects will receive 1 dose at Week 12.
• Biological: Meningococcal vaccine
  This vaccine is used to prevent meningococcal diseases (infection of the brain and spinal cord) and blood poisoning. All subjects will receive 1 dose at Week 12.

Study Arms

• Experimental: Tralokinumab

  Week 0 to 16:> Tralokinumab will be given as subcutaneous injections. >

  > Subjects will receive a tralokinumab loading dose at Day 0 followed by tralokinumab injection regimen A. The last administration will occur at Week 14.

  Interventions:

  • Drug: Tralokinumab
  • Biological: Tdap vaccine
  • Biological: Meningococcal vaccine
• Placebo Comparator: Placebo

  Placebo (dummy treatment) will be given as subcutaneous injections. >

  > Subjects will receive a placebo loading dose at Day 0 followed by placebo injection regimen A. The last administration will occur at Week 14.

  Interventions:

  • Drug: Placebo
  • Biological: Tdap vaccine
  • Biological: Meningococcal vaccine

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 9, 2020): 215
• Original Estimated Enrollment (submitted: June 8, 2018): 200
• Actual Study Completion Date: November 22, 2019
• Actual Primary Completion Date: September 17, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:>

• Age 18 to 54 years>
• Diagnosis of AD as defined by Hanifin and Rajka (1980) criteria for AD>
• History 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>
• An EASI score of ≥12 at screening and 16 at baseline>
• An IGA score of ≥3 at screening and at baseline >
• Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation>

Exclusion Criteria:>

• Subjects for whom administration of the meningococcal vaccine provided in this trial is contraindicated or medically inadvisable, according to local label of the vaccine>
• Subjects for whom administration of the tetanus, diphtheria, and pertussis vaccine provided in this trial is contraindicated or medically inadvisable, according to local label of the vaccine>
• 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 medications and/or systemic corticosteroids within 4 weeks prior to randomisation>
• Treatment with the topical medications topical corticosteroids (TCS), topical calcineurin inhibitor (TCI) or phosphodiesterase 4 (PDE-4) inhibitor within 2 weeks prior to randomisation>
• Receipt of any vaccine (except influenza virus vaccines) within 3 months prior to screening, any meningococcal vaccine within 1 year prior to screening, or any tetanus-, diphtheria-, or pertussis-containing vaccine within 5 years prior to screening>
• Receipt of any marketed (i.e. immunoglobulin, anti-IgE) or investigational biologic agent, including dupilumab>
• History of any active skin infection within 1 week prior to randomisation>
• History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to randomisation

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 54 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT03562377
• Other Study ID Numbers: LP0162-1341
• 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
• Plan Description: De-identified IPD can be made available to researchers in a closed environment for a specified period of time.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: Data is 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

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

Investigators

• Study Director: Medical Expert; LEO Pharma

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