This phase 2b study is designed to evaluate the safety and efficacy of tezepelumab as a monotherapy and explore its efficacy as adjunct therapy in subjects with moderate-to-severe atopic dermatitis (AD).
All subjects will receive a subcutaneous (SC) dose of either investigational product or placebo as the first dose on day 1. Subjects who are determined to be non-responders in Part A will receive tezepelumab SC every 2 weeks (Q2W) following completion of all week 16 study activities. Nonresponders are defined as those subjects who have not achieved at least a 50% improvement in Eczema Area and Severity Index (EASI) at week 16 compared to baseline (day 1). Safety follow-up is 18 weeks after the end of treatment (EOT) visit (20 weeks after the final dose of investigational product).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
251
Solution for injection
Placebo solution for injection
Number of Participants With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) (IGA 0/1) at Week 16
The IGA allows investigators to assess overall disease severity at 1 given time point and consists of a 6-point severity scale from clear to severe disease * 0 = clear * 1 = almost clear * 2 = mild disease * 3 = moderate disease * 4 = severe disease * 5 = very severe disease The IGA uses clinical characteristics of erythema, infiltration, papulation, oozing, and crusting as guidelines for the overall severity assessment (Breuer et al, 2004). Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
Time frame: Week 16
Number of Participants Who Experienced a 75% Reduction From Baseline in Eczema Area and Severity Index (EASI 75) at Week 16
The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification). A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
Time frame: Baseline and Week 16
Number of Participants Who Experienced a 50% or 90% Reduction From Baseline in Eczema Area and Severity Index (EASI 50/90) at Week 16
The EASI evaluates 4 natural anatomical regions for severity and extent of key disease signs and focuses on key acute and chronic signs of inflammation (ie, erythema, induration/papulation, excoriation, and lichenification). A reduction in the EASI score indicates an improvement in severity. Participants who took rescue medication between Day 29 to Week 16 were considered non-responders.
Time frame: Baseline and Week 16
Time to Achievement of 50%, 75% or 90% Reduction From Day 1 in Eczema Area and Severity Index (EASI 50/75/90)
Time frame: Day 1 up to End of Study Visit (Week 70)
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Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) at Week 16
The SCORAD is a clinical tool for assessing the severity (ie, extent, intensity) of atopic dermatitis (AD). The tool evaluates the extent and intensity of the AD lesions, along with subjective symptoms (Kunz et al, 1997). The total score ranges from 0 to 103, with higher values indicating more severe disease. A negative change from baseline indicates an improvement in severity of disease.
Time frame: Baseline and Week 16
Change From Baseline in Pruritus Numeric Rating Scale (NRS) at Week 16
Pruritus was assessed using an NRS (0-10) with 0 = no itch and 10 = worst imaginable itch. A negative change from baseline indicates an improvement in symptoms.
Time frame: Baseline and Week 16
Serum Trough Concentrations of Tezepelumab After Q2W or Q4W Administration
Switchers were included up to Week 16 and were then excluded from the analysis after switching. All Tezepelumab participants received 420 mg of Tezepelumab on Day 1.
Time frame: Pre-dose on Day 1, Week 2, 4, 12, 16, 24, 32, 40, 48, 50, 52, 58 and 70
Serum Trough Concentrations of Tezepelumab After Switching to 420 mg Q2W Administration After Week 16
Time frame: Pre-dose on Week 24, 32, 40, 48, 50, 52, 58 and 70