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

Study Overview
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Brief Summary
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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
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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: > 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.> 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.

Official Title
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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

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Tralokinumab
* Drug: Placebo
* Biological: Tdap vaccine
* Biological: Meningococcal vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 54 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tralokinumab<br>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<br>* 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.<br>Biological: Tdap vaccine<br>* Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. All subjects will receive 1 dose at Week 12.<br>Biological: Meningococcal vaccine<br>* 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.<br>|
| Placebo Comparator: Placebo<br>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. | Drug: Placebo<br>* Placebo contains the same excipients in the same concentration only lacking tralokinumab.<br>Biological: Tdap vaccine<br>* Tetanus (lockjaw), diphtheria (infection of the nose and throat), and pertussis (whooping cough) vaccine. All subjects will receive 1 dose at Week 12.<br>Biological: Meningococcal vaccine<br>* 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.<br>|

What is the study measuring?
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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 |