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NCT Number: NCT05583227

Efficacy and Safety of Tezepelumab in Patients With Eosinophilic Esophagitis

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).

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Eosinophilic Esophagitis Digestive System Diseases Eosinophilia Esophageal Diseases Esophagitis Gastroenteritis Gastrointestinal Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Leukocyte Disorders

Age range

12 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Research Site, Elizabeth Vale, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.
  • Weight ≥ 40 kg at Visit 1
  • Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.
  • Participants who have symptomatic EoE as defined by a history of on average at least 2 episodes of dysphagia (any severity of food going down slowly or being stuck in the throat) per week in the 4 weeks prior to Visit 1.
  • Must remain on a stabilized diet for at least 8 weeks prior to Visit 1 and during the course of the study (stable diet is defined as no initiation of single or multiple elimination diets or reintroduction of previously eliminated food groups).
  • May be on any background PPI and/or STC, during the course of the study, as long as background medications have been stable for at least 8 weeks prior to the screening/run-in period (Visit 1) and there is agreement not to change background medication or dosage unless medically indicated, during the screening/run-in and treatment period.
  • Participants currently on leukotriene inhibitors and/or steroid treatments for asthma or allergies that are inhaled or administered intranasally, must report a stable dose for at least 4 weeks prior to the screening/run-in period (Visit 1).
  • If a medication for EoE (for example PPI and/or STC) is discontinued prior to the screening/run-in, there should be a washout period of at least 8 weeks prior to Visit 1. Discontinuation of any marketed biologic (monoclonal or polyclonal antibody) should have a washout period of 4 months or 5 half-lives prior to Visit 1, whichever is longer.
  • Participants should have previously documented standard of care treatment, which could include PPI and/or STC and/or diet.

Exclusion criteria

  • Other gastrointestinal disorders such as active Helicobacter pylori infection, history of achalasia, esophageal varices, Crohn's disease, ulcerative colitis, inflammatory bowel disease, celiac disease, eosinophilic enteritis, colitis, diverticulitis, irritable bowel syndrome, or other clinically significant gastrointestinal conditions as per Investigator discretion.
  • Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.
  • Use of a feeding tube, or having a pattern of not eating solid food >3 days of week. Solid food is defined as food that requires chewing before swallowing.
  • Hypereosinophilic syndrome
  • EGPA vasculitis
  • Esophageal dilation performed within 8 weeks prior to screening.

Treatment and study plan

Tezepelumab

Biological

Tezepelumab subcutaneous injection

Placebo

Other

Placebo subcutaneous injection

Primary outcomes

  1. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels

    Time frame: Week 24

    Peak esophageal eosinophil count per HPF determined by histological analysis of 2-4 biopsies from each of the proximal, mid, and distal esophagus.

  2. Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score

    Time frame: Week 24

    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.

Secondary outcomes

  1. Change from baseline in EoE EREFS (Endoscopic reference score )

    Time frame: Week 24, Week 52

    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.

  2. Change from baseline in EoE-HSS (Histologic scoring system) grade score

    Time frame: Week 24

    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).

  3. Change from baseline in EoE-HSS (Histologic scoring system) stage score

    Time frame: Week 24

    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).

  4. Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels

    Time frame: Week 52

    The peak esophageal eosinophil count is based on 2-4 esophageal biopsies from 2-3 locations.

  5. Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score

    Time frame: Week 52

    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.

  6. 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

    Time frame: Week 52

    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.

  7. 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)

    Time frame: Week 52

    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.

  8. Total endoscopic remission of total EREFS score of 0 across all esophageal levels

    Time frame: Week 52

    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.

Other outcomes

  1. Change from baseline in peak esophageal eosinophil count (EOS/HPF)

    Time frame: Week 24, Week 52

    The EOS/HPF is a method of evaluating esophageal inflammation by histological response of eosinophils per high power field (HPF).

  2. Changes from baseline in PEESS Module at Week 24 (adolescents only).

    Time frame: Week 24, Week 52

    The PEESS is an 20-item assessment of EoE symptom severity and frequency validated for use in patients aged 8 to 18 years. The overall score ranges from 0 to 80, with higher scores representing more severe and frequent EoE symptoms.

  3. Change from baseline in EoE-HSS (Histologic scoring system) stage score

    Time frame: Week 52

    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. Extent (stage) of abnormalities is scored using a 4-point scale (0 normal; 3 maximum change).

  4. Change from baseline in EoE-HSS (Histologic scoring system) grade score

    Time frame: Week 52

    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) of abnormalities is scored using a 4-point scale (0 normal; 3 maximum change).

  5. Serum tezepelumab concentration

    Time frame: Weeks 0, 4, 12, 24, and 52

    PK samples will be collected pre-dose. Tezepelumab concentration in serum is determined using bioanalytical method.

  6. Anti-drug antibody

    Time frame: Weeks 0, 12, 24, and 52

    Anti-drug antibody is determined using bioanalytical method.

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Collaborators

  • Amgen

Registry information

Official study title

A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING).

Acronym: CROSSING

Important dates

Study start
2022
Primary completion
2026
Study completion
2027
First posted
Oct 17, 2022
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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