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

Phase 2

Completed

Interventions: Drug: Placebo
Drug: Tralokinumab
Biological: Tdap vaccine
Biological: Meningococcal vaccine

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Tralokinumab	Tdap vaccine	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.
Placebo	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.
Placebo	Meningococcal vaccine	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.
Tralokinumab	Meningococcal vaccine	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.
Placebo	Tdap vaccine	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.
Tralokinumab	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.

Primary Outcome Measures

Name	Time	Method
Positive Anti-tetanus Response at Week 16	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	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 at least a 3-fold increase compared to Week 12.

Secondary Outcome Measures

Name	Time	Method
Number of AEs.	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).	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.
Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16.	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.
Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16	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).

Locations (2): LEO Pharma Investigational Site
🇨🇦
Verdun, Quebec, Canada
Leo Pharma Investigational Site
🇺🇸
Spokane, Washington, United States