Clinical trial NCT03562377: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atopic Dermatitis
Lead sponsor: LEO Pharma
Sponsor class: INDUSTRY
First posted: 2018-06-19
Enrollment: 215
Sex: ALL
Minimum age (years): 18
Maximum age (years): 54
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Positive Anti-tetanus Response at Week 16
timeFrame: Week 12 to Week 16
measure: Positive Anti-meningococcal Response at Week 16
timeFrame: Week 12 to Week 16
Secondary outcomes:
measure: Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
timeFrame: Week 0 to Week 16
measure: Participants Achieving at Least 75% Reduction in Eczema Area and Severity Index (EASI) at Week 16.
timeFrame: Week 0 to Week 16
measure: Number of AEs.
timeFrame: Week 0 to Week 16
measure: Presence of Anti-drug Antibodies (ADA).
timeFrame: Week 0 to Week 16
Other outcomes:
Locations:
city: Fort Smith
country: United States
facility: Leo Pharma Investigational Site
state: Arkansas
city: Bakersfield
country: United States
facility: LEO Pharma Investigational Site
state: California
city: Beverly Hills
country: United States
facility: Leo Pharma Investigational Site
state: California
city: Fountain Valley
country: United States
facility: Leo Pharma Investigational Site
state: California
city: Los Angeles
country: United States
facility: Leo Pharma Investigational Site
state: California
city: Los Angeles
country: United States
facility: Leo Pharma Investigational Site
state: California
city: Los Angeles
country: United States
facility: Leo Pharma Investigational Site
state: California
city: Newport Beach
country: United States
facility: Leo Pharma Investigational Site
state: California
city: San Diego
country: United States
facility: LEO Pharma Investigational Site
state: California
city: Centennial
country: United States
facility: LEO Pharma Investigational Site
state: Colorado
city: Denver
country: United States
facility: LEO Pharma Investigational Site
state: Colorado
city: Thornton
country: United States
facility: LEO Pharma Investigational Site
state: Colorado
city: Coral Gables
country: United States
facility: Leo Pharma Investigational Site
state: Florida
city: Doral
country: United States
facility: Leo Pharma Investigational Site
state: Florida
city: Hialeah
country: United States
facility: Leo Pharma Investigational Site
state: Florida
city: Atlanta
country: United States
facility: LEO Pharma Investigational Site
state: Georgia
city: New Albany
country: United States
facility: Leo Pharma Investigational Site
state: Indiana
city: South Bend
country: United States
facility: Leo Pharma Investigational Site
state: Indiana
city: Bangor
country: United States
facility: LEO Pharma Investigational Site
state: Maine
city: Boston
country: United States
facility: Leo Pharma Investigational Site
state: Massachusetts
city: Brighton
country: United States
facility: LEO Pharma Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Leo Pharma Investigational Site
state: Michigan
city: Southfield
country: United States
facility: LEO Pharma Investigational Site
state: Michigan
city: Missoula
country: United States
facility: Leo Pharma Investigational Site
state: Montana
city: East Windsor
country: United States
facility: Leo Pharma Investigational Site
state: New Jersey
city: Brooklyn
country: United States
facility: LEO Pharma Investigational Site
state: New York
city: Cortland
country: United States
facility: Leo Pharma Investigational Site
state: New York
city: Forest Hills
country: United States
facility: Leo Pharma Investigational Site
state: New York
city: New York
country: United States
facility: Leo Pharma Investigational Site
state: New York
city: Cincinnati
country: United States
facility: Leo Pharma Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: LEO Pharma Investigational Site
state: Ohio
city: Gahanna
country: United States
facility: LEO Pharma Investigational Site
state: Ohio
city: Medford
country: United States
facility: LEO Pharma Investigational Site
state: Oregon
city: Chattanooga
country: United States
facility: Leo Pharma Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Leo Pharma Investigational Site
state: Texas
city: Dallas
country: United States
facility: LEO Pharma Investigational Site
state: Texas
city: Frisco
country: United States
facility: Leo Pharma Investigational Site
state: Texas
city: South Burlington
country: United States
facility: Leo Pharma Investigational Site
state: Vermont
city: Spokane
country: United States
facility: Leo Pharma Investigational Site
state: Washington
city: Edmonton
country: Canada
facility: LEO Pharma Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: LEO Pharma Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: LEO Pharma Investigational Site
state: British Colombia
city: Saint John's
country: Canada
facility: LEO Pharma Investigational Site
state: New Foundland & Labrador
city: Hamilton
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: London
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Oakville
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Peterborough
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Richmond Hill
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: LEO Pharma Investigational Site
state: Ontario
city: Verdun
country: Canada
facility: LEO Pharma Investigational Site
state: Quebec
Study officials:
affiliation: LEO Pharma
name: Medical Expert
role: STUDY_DIRECTOR
References:
citation: 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.