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Trial record 9 of 14 for:    tezepelumab | Recruiting, Active, not recruiting Studies
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Efficacy and Safety of Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING)

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ClinicalTrials.gov Identifier: NCT05583227
Recruitment Status : Recruiting
First Posted : October 17, 2022
Last Update Posted : May 8, 2024
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief 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).

Condition or disease Intervention/treatment Phase
Eosinophilic Esophagitis Biological: Tezepelumab Other: Placebo Phase 3

Detailed 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 360 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Subjects will be randomized in a 1:1:1 ratio to receive either low dose of tezepelumab, high dose of tezepelumab, or placebo.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING).
Actual Study Start Date : November 10, 2022
Estimated Primary Completion Date : May 1, 2026
Estimated Study Completion Date : January 8, 2027

Resource links provided by the National Library of Medicine

Drug Information available for: Tezepelumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Tezepelumab Low Dose
Tezepelumab subcutaneous injections, in accessorised pre-filled syringes
 Biological: Tezepelumab
Tezepelumab subcutaneous injection
Experimental: Tezepelumab High Dose
Tezepelumab subcutaneous injections, in accessorised pre-filled syringes
 Biological: Tezepelumab
Tezepelumab subcutaneous injection
Placebo Comparator: Placebo
Placebo subcutaneous injections, in accessorised pre-filled syringes
 Other: Placebo
Placebo subcutaneous injection


Outcome Measures
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Primary Outcome Measures :
  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 Outcome Measures :
  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. Response of achieving clinico-histological remission [ Time Frame: Week 24, Week 52 ]
    Achieving pre-determined histologic and symptomatic remission thresholds.


Other Outcome Measures:
  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.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   12 Years to 80 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05583227


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: Carebox Healthcare Solutions Inc 1-844-432-3890 az-crossing@careboxhealth.com

Locations
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Sponsors and Collaborators
AstraZeneca
Amgen
More Information
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Additional Information:

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT05583227    
Other Study ID Numbers: D5244C00001
2022-001294-31 ( EudraCT Number )
First Posted: October 17, 2022    Key Record Dates
Last Update Posted: May 8, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
Chronic Esophagitis
Eosinophilic Esophagitis
Eosinophilic
Additional relevant MeSH terms:
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Esophagitis
Eosinophilic Esophagitis
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Eosinophilia
Leukocyte Disorders
 Hematologic Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs