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

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

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.

Study Overview

• Status: Completed
• Conditions: Atopic Dermatitis
• Intervention / Treatment: Drug: Tralokinumab; Biological: Tdap vaccine; Biological: Meningococcal vaccine; Drug: Placebo

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
• Enrollment (Actual): 215
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5K 1X3
      • LEO Pharma Investigational Site
    • Edmonton, Alberta, Canada, T6G 1C3
      • LEO Pharma Investigational Site
  • British Colombia
    • Vancouver, British Colombia, Canada, V6H 4E1
      • LEO Pharma Investigational Site
  • New Foundland & Labrador
    • Saint John's, New Foundland & Labrador, Canada, A1A 4Y3
      • LEO Pharma Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8S 1G5
      • LEO Pharma Investigational Site
    • London, Ontario, Canada, N6H 5L5
      • LEO Pharma Investigational Site
    • Oakville, Ontario, Canada, L6J 7W5
      • LEO Pharma Investigational Site
    • Peterborough, Ontario, Canada, K9J 5K2
      • LEO Pharma Investigational Site
    • Richmond Hill, Ontario, Canada, L4B 1A5
      • LEO Pharma Investigational Site
    • Toronto, Ontario, Canada, M4V 1R2
      • LEO Pharma Investigational Site
    • Windsor, Ontario, Canada, N8X 2G1
      • LEO Pharma Investigational Site
  • Quebec
    • Verdun, Quebec, Canada, H4G 3E7
      • LEO Pharma Investigational Site
• United States
  • Arkansas
    • Fort Smith, Arkansas, United States, 72916
      • LEO Pharma Investigational Site
  • California
    • Bakersfield, California, United States, 93301
      • LEO Pharma Investigational Site
    • Beverly Hills, California, United States, 90212
      • LEO Pharma Investigational Site
    • Fountain Valley, California, United States, 92708
      • LEO Pharma Investigational Site
    • Los Angeles, California, United States, 90025
      • LEO Pharma Investigational Site
    • Los Angeles, California, United States, 90045
      • LEO Pharma Investigational Site
    • Los Angeles, California, United States, 90057
      • LEO Pharma Investigational Site
    • Newport Beach, California, United States, 92660
      • LEO Pharma Investigational Site
    • San Diego, California, United States, 92123
      • LEO Pharma Investigational Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • LEO Pharma Investigational Site
    • Denver, Colorado, United States, 80045
      • LEO Pharma Investigational Site
    • Thornton, Colorado, United States, 80233
      • LEO Pharma Investigational Site
  • Florida
    • Coral Gables, Florida, United States, 33134
      • LEO Pharma Investigational Site
    • Doral, Florida, United States, 33122
      • LEO Pharma Investigational Site
    • Hialeah, Florida, United States, 33012
      • LEO Pharma Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • LEO Pharma Investigational Site
  • Indiana
    • New Albany, Indiana, United States, 47150
      • LEO Pharma Investigational Site
    • South Bend, Indiana, United States, 46617
      • LEO Pharma Investigational Site
  • Maine
    • Bangor, Maine, United States, 04401
      • LEO Pharma Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • LEO Pharma Investigational Site
    • Brighton, Massachusetts, United States, 02135
      • LEO Pharma Investigational Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48103
      • LEO Pharma Investigational Site
    • Southfield, Michigan, United States, 48034
      • LEO Pharma Investigational Site
  • Montana
    • Missoula, Montana, United States, 59808
      • LEO Pharma Investigational Site
  • New Jersey
    • East Windsor, New Jersey, United States, 08520
      • LEO Pharma Investigational Site
  • New York
    • Brooklyn, New York, United States, 11201
      • LEO Pharma Investigational Site
    • Cortland, New York, United States, 13045
      • LEO Pharma Investigational Site
    • Forest Hills, New York, United States, 11375
      • LEO Pharma Investigational Site
    • New York, New York, United States, 10021
      • LEO Pharma Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • LEO Pharma Investigational Site
    • Cincinnati, Ohio, United States, 45231
      • LEO Pharma Investigational Site
    • Gahanna, Ohio, United States, 43230
      • LEO Pharma Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • LEO Pharma Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • LEO Pharma Investigational Site
  • Texas
    • Austin, Texas, United States, 78759
      • LEO Pharma Investigational Site
    • Dallas, Texas, United States, 75225
      • LEO Pharma Investigational Site
    • Frisco, Texas, United States, 75034
      • LEO Pharma Investigational Site
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • LEO Pharma Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202
      • LEO Pharma Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 randomization
• Treatment with systemic immunosuppressive/immunomodulating medications and/or systemic corticosteroids within 4 weeks prior to randomization
• Treatment with the topical medications topical corticosteroids (TCS), topical calcineurin inhibitor (TCI) or phosphodiesterase 4 (PDE-4) inhibitor within 2 weeks prior to randomization
• 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 randomization
• History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to randomization

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	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.; 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.
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.	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.; Drug: Placebo; Placebo contains the same excipients in the same concentration only lacking tralokinumab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive Anti-tetanus Response at 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.	Week 12 to Week 16
Positive Anti-meningococcal Response at 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 at least a 3-fold increase compared to Week 12.	Week 12 to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at 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).	Week 0 to Week 16
Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at 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.	Week 0 to Week 16
Number of AEs.	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.	Week 0 to Week 16
Presence of Anti-drug Antibodies (ADA).	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.	Week 0 to Week 16

Collaborators and Investigators

• Sponsor: LEO Pharma
• Investigators: Study Director: Medical Expert, LEO Pharma

Publications and helpful links

General Publications

• Simpson EL, Merola JF, Silverberg JI, Reich K, Warren RB, Staumont-Salle D, Girolomoni G, Papp K, de Bruin-Weller M, Thyssen JP, Zachariae R, Olsen CK, Wollenberg A. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br J Dermatol. 2022 Dec;187(6):888-899. doi: 10.1111/bjd.21867. Epub 2022 Oct 26.

Study record dates

Study Major Dates

• Study Start (Actual): July 13, 2018
• Primary Completion (Actual): September 17, 2019
• Study Completion (Actual): November 22, 2019

Study Registration Dates

• First Submitted: June 8, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Skin Diseases; Skin Diseases, Genetic; Skin Diseases, Eczematous; Dermatitis, Atopic; Dermatitis; Eczema; Immunologic Factors; Physiological Effects of Drugs; Vaccines
• Other Study ID Numbers: LP0162-1341

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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: De-identified Individual Participant Data can be made available to researchers and is subject to approved scientifically sound research proposal and signed data-sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No