A randomized, double-blind, placebo-controlled multicenter, phase 3 study to evaluate the efficacy and safety of tezepelumab administered subcutaneously (SC) using an accessorized pre-filled syringe (APFS) versus placebo in adult and adolescent patients with eosinophilic esophagitis (EoE).
The study consists of a screening period of 2 to 8 weeks and a 52-week randomized double-blind placebo-controlled treatment period. After completion of the treatment period, participants will be eligible to participate in an optional active treatment extension period (lasting for 24 weeks), followed by a 12-week off-treatment safety follow-up period. Participants who will not participate in the extension period will participate in a 12-week off-treatment safety follow-up period following completion of the 52-week treatment period. This study will randomize approximately 360 participants. The participants will be randomized at 1:1:1 ratio to the 3 treatment arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
368
Tezepelumab subcutaneous injection
Tezepelumab subcutaneous injection
Placebo subcutaneous injection
Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels
Peak esophageal eosinophil count per HPF determined by histological analysis of 2-4 biopsies from each of the proximal, mid, and distal esophagus.
Time frame: Week 24
Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score
The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia.
Time frame: Week 24
Change from baseline in EoE EREFS (Endoscopic reference score )
The EoE EREFS is a scoring system for assessing the presence and severity of the major endoscopic signs of EoE, including esophageal edema, rings, exudates, furrows, and stricture. EoE endoscopic appearances will be analyzed by the EoE-EREFS, a scoring system for inflammatory and fibrostenotic features of the disease. Proximal and distal esophageal areas will be scored, with the score for each region ranging from 0 to 9, and the overall score ranging from 0 to 18. Higher scores indicate more extensive disease.
Time frame: Week 24, Week 52
Change from baseline in EoE-HSS (Histologic scoring system) grade score
EoE HSS is a histology scoring system for esophageal biopsies that evaluates 8 features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change).
Time frame: Week 24
Change from baseline in EoE-HSS (Histologic scoring system) stage score
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Research Site
Phoenix, Arizona, United States
Research Site
Little Rock, Arkansas, United States
Research Site
Los Angeles, California, United States
Research Site
Aurora, Colorado, United States
Research Site
Inverness, Florida, United States
Research Site
Jacksonville, Florida, United States
Research Site
Saint Augustine, Florida, United States
Research Site
Normal, Illinois, United States
Research Site
Iowa City, Iowa, United States
Research Site
Topeka, Kansas, United States
...and 115 more locations
EoE HSS is a histology scoring system for esophageal biopsies that evaluates 8 features: eosinophil density, basal zone hyperplasia, eosinophil abscesses, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. Severity (grade) and extent (stage) of abnormalities are scored using a 4-point scale (0 normal; 3 maximum change).
Time frame: Week 24
Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels
The peak esophageal eosinophil count is based on 2-4 esophageal biopsies from 2-3 locations.
Time frame: Week 52
Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score
The Dysphagia Symptom Questionnaire (DSQ) captures the presence and severity of dysphagia symptoms in the past day in a 4-item questionnaire. The DSQ score is calculated over 14-day periods and ranges from 0 to 84, with a lower score indicating less severe dysphagia.
Time frame: Week 52
Endoscopic response of total EREFS score of 0 to ≤2 with no score > 1 for any of the components and no worsening in any individual component from baseline accross all esophageal levels
EoE endoscopic appearances will be analyzed by the EoE-EREFS, a scoring system for inflammatory and fibrostenotic features of the disease. For each of the EREFS compontents a maximum score across proximal, mid and distal esophageal areas will be selected, with the scores for edema and stricture ranging from 0 to 1, exudates and furrows ranging from 0 to 2, fixed rings ranging from 0 to 3, and overall maximum score ranging from 0 to 9.
Time frame: Week 52
Endoscopic inflammatory remission of EREFS inflammatory subscore (including edema, exudate, and furrows components) of 0 with no worsening in rings or stricture from baseline across all esophageal levels)
EoE endoscopic appearances will be analyzed by the EoE-EREFS, a scoring system for inflammatory and fibrostenotic features of the disease. For each of the EREFS compontents a maximum score across proximal, mid and distal esophageal areas will be selected, with the scores for edema and stricture ranging from 0 to 1, exudates and furrows ranging from 0 to 2, fixed rings ranging from 0 to 3, and overall maximum score ranging from 0 to 9.
Time frame: Week 52
Total endoscopic remission of total EREFS score of 0 across all esophageal levels
EoE endoscopic appearances will be analyzed by the EoE-EREFS, a scoring system for inflammatory and fibrostenotic features of the disease. For each of the EREFS compontents a maximum score across proximal, mid and distal esophageal areas will be selected, with the scores for edema and stricture ranging from 0 to 1, exudates and furrows ranging from 0 to 2, fixed rings ranging from 0 to 3, and overall maximum score ranging from 0 to 9.
Time frame: Week 52