Efficacy and Safety of Tezepelumab in Patients With Eosinophilic Esophagitis

Eosinophilic Esophagitis Clinical Trial

— CROSSING  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05583227
• Other study ID #: D5244C00001
• Secondary ID: 2022-001294-31
• Status: Recruiting
• Phase: Phase 3
• Start date: November 10, 2022
• Est. completion date: January 8, 2027

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 360
• Est. completion date: January 8, 2027
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Participant must be 12 to 80 years of age inclusive, at the time of signing the informed consent/assent.

2. Weight = 40 kg at Visit 1

3. Established diagnosis of EoE with a previous EGD and esophageal biopsy confirming a diagnosis of EoE.

4. 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.

5. 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).

6. 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.

7. 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).

8. 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.

9. Participants should have previously documented standard of care treatment, which could include PPI and/or STC and/or diet.

Exclusion Criteria:

1. 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.

2. Esophageal stricture that prevents the easy passage of a standard endoscope or any critical esophageal stricture that requires dilation at screening.

3. 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.

4. Hypereosinophilic syndrome

5. EGPA vasculitis

6. Esophageal dilation performed within 8 weeks prior to screening.

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Biological:
• Tezepelumab
Tezepelumab subcutaneous injection
• Tezepelumab
Tezepelumab subcutaneous injection

Other:
• Placebo
Placebo subcutaneous injection

Locations

Country	Name	City	State
Australia	Research Site	Elizabeth Vale
Australia	Research Site	Kogarah
Australia	Research Site	Mitcham
Australia	Research Site	South Brisbane
Australia	Research Site	Woolloongabba
Austria	Research Site	Graz
Austria	Research Site	Wels-Grieskirchen
Austria	Research Site	Wien
Belgium	Research Site	Brugge
Belgium	Research Site	Edegem
Belgium	Research Site	Gent
Belgium	Research Site	Leuven
Brazil	Research Site	Botucatu
Brazil	Research Site	Brasilia
Brazil	Research Site	Caxias do Sul
Brazil	Research Site	Curitiba
Brazil	Research Site	Curitiba
Brazil	Research Site	Porto Alegre
Brazil	Research Site	Porto Alegre
Brazil	Research Site	São José do Rio Preto
Brazil	Research Site	Sao Paulo
Canada	Research Site	Hamilton	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	Niagara Falls	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Windsor	Ontario
China	Research Site	Beijing
China	Research Site	Beijing
China	Research Site	Changsha
China	Research Site	Guangzhou
China	Research Site	Guangzhou
China	Research Site	Hangzhou
China	Research Site	Nanjing
China	Research Site	Shanghai
China	Research Site	Shanghai
China	Research Site	Shenyang
China	Research Site	Tianjin
China	Research Site	Wuhan
China	Research Site	Zhengzhou
Czechia	Research Site	Brno
Czechia	Research Site	Hradec Kralove
Czechia	Research Site	Praha
Denmark	Research Site	Aalborg
Denmark	Research Site	Køge
Denmark	Research Site	Odense
Finland	Research Site	Hämeenlinna
Finland	Research Site	Helsinki
Finland	Research Site	Helsinki
Finland	Research Site	Helsinki
Finland	Research Site	Kuopio
Finland	Research Site	Turku
Germany	Research Site	Frankfurt
Germany	Research Site	Landsberg
Germany	Research Site	München
Germany	Research Site	München
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Athens
Greece	Research Site	Thessaloniki
Israel	Research Site	Haifa
Israel	Research Site	Holon
Israel	Research Site	Jerusalem
Israel	Research Site	Petah Tikva
Israel	Research Site	Petah Tikva
Israel	Research Site	Tel Aviv
Israel	Research Site	Tel Aviv
Israel	Research Site	Tel Hashomer
Italy	Research Site	Bologna
Italy	Research Site	Milano
Italy	Research Site	Napoli
Italy	Research Site	Napoli
Italy	Research Site	Padova
Italy	Research Site	Pisa
Italy	Research Site	Roma
Italy	Research Site	Roma
Italy	Research Site	Rozzano
Italy	Research Site	Verona
Japan	Research Site	Akita-shi
Japan	Research Site	Fukuoka-shi
Japan	Research Site	Himeji
Japan	Research Site	Hiroshima-shi
Japan	Research Site	Isehara-shi
Japan	Research Site	Kawasaki-shi
Japan	Research Site	Kitakyushu-shi
Japan	Research Site	Maebashi-shi
Japan	Research Site	Minato-ku
Japan	Research Site	Minato-ku
Japan	Research Site	Osaka
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Shinjuku-ku
Japan	Research Site	Yamagata-shi
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Nijmegen
Netherlands	Research Site	Rotterdam
New Zealand	Research Site	Christchurch
New Zealand	Research Site	Grafton
New Zealand	Research Site	Hamilton
New Zealand	Research Site	Newtown
New Zealand	Research Site	Otahuhu
Norway	Research Site	Ålesund
Norway	Research Site	Lørenskog
Norway	Research Site	Lørenskog
Norway	Research Site	Oslo
Norway	Research Site	Oslo
Norway	Research Site	Tromsø
Slovakia	Research Site	Kosice
Slovakia	Research Site	Martin
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Bilbao (Vizcaya)
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Madrid
Spain	Research Site	Pamplona
Spain	Research Site	Sevilla
Spain	Research Site	Sevilla
Spain	Research Site	Tomelloso
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Sweden	Research Site	Trollhättan
Sweden	Research Site	Uppsala
United Kingdom	Research Site	Brighton
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United States	Research Site	Atlanta	Georgia
United States	Research Site	Aurora	Colorado
United States	Research Site	Boston	Massachusetts
United States	Research Site	Brooklyn	New York
United States	Research Site	Chapel Hill	North Carolina
United States	Research Site	Charlottesville	Virginia
United States	Research Site	Chesterfield	Michigan
United States	Research Site	Chicago	Illinois
United States	Research Site	Cincinnati	Ohio
United States	Research Site	Greenville	South Carolina
United States	Research Site	Houston	Texas
United States	Research Site	Inverness	Florida
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jacksonville	Florida
United States	Research Site	Lincoln	Nebraska
United States	Research Site	Little Rock	Arkansas
United States	Research Site	Los Angeles	California
United States	Research Site	Nashville	Tennessee
United States	Research Site	Normal	Illinois
United States	Research Site	Ocean City	New Jersey
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Phoenix	Arizona
United States	Research Site	Saint Augustine	Florida
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Salt Lake City	Utah
United States	Research Site	Smithfield	Pennsylvania
United States	Research Site	Topeka	Kansas
United States	Research Site	White Marsh	Maryland
United States	Research Site	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Amgen

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Brazil,  Canada,  China,  Czechia,  Denmark,  Finland,  Germany,  Greece,  Israel,  Italy,  Japan,  Netherlands,  New Zealand,  Norway,  Slovakia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change from baseline in peak esophageal eosinophil count (EOS/HPF)	The EOS/HPF is a method of evaluating esophageal inflammation by histological response of eosinophils per high power field (HPF).	Week 24, Week 52
Other	Changes from baseline in PEESS Module at Week 24 (adolescents only).	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.	Week 24, Week 52
Other	Change from baseline in EoE-HSS (Histologic scoring system) stage 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. Extent (stage) of abnormalities is scored using a 4-point scale (0 normal; 3 maximum change).	Week 52
Other	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) of abnormalities is scored using a 4-point scale (0 normal; 3 maximum change).	Week 52
Other	Serum tezepelumab concentration	PK samples will be collected pre-dose. Tezepelumab concentration in serum is determined using bioanalytical method.	Weeks 0, 4, 12, 24, and 52
Other	Anti-drug antibody	Anti-drug antibody is determined using bioanalytical method.	Weeks 0, 12, 24, and 52
Primary	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.	Week 24
Primary	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.	Week 24
Secondary	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.	Week 24, Week 52
Secondary	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).	Week 24
Secondary	Change from baseline in EoE-HSS (Histologic scoring system) stage 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).	Week 24
Secondary	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.	Week 52
Secondary	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.	Week 52
Secondary	Response of achieving clinico-histological remission	Achieving pre-determined histologic and symptomatic remission thresholds.	Week 24, Week 52

External Links

•   This webpage was designed to learn about the work AstraZeneca is doing to develop Eosinophilic Esophagitis (EoE) treatments and find out how you could get involved in a clinical trial.