Clinical trial NCT05583227: Efficacy and Safety of Tezepelumab in Patients With Eosinophilic Esophagitis
Official title: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Tezepelumab in Patients With Eosinophilic Esophagitis (CROSSING).
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Eosinophilic Esophagitis
Keywords: Chronic Esophagitis
Eosinophilic Esophagitis
Eosinophilic
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Amgen
First posted: 2022-10-17
Enrollment: 352
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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).

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.

Eligibility 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.

Primary outcomes:
measure: Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels
timeFrame: Week 24
measure: Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score
timeFrame: Week 24
Secondary outcomes:
measure: Change from baseline in EoE EREFS (Endoscopic reference score )
timeFrame: Week 24, Week 52
measure: Change from baseline in EoE-HSS (Histologic scoring system) grade score
timeFrame: Week 24
measure: Change from baseline in EoE-HSS (Histologic scoring system) stage score
timeFrame: Week 24
measure: Histologic response of peak esophageal eosinophil per HPF count of ≤ 6 across all available esophageal levels
timeFrame: Week 52
measure: Change from baseline in DSQ (Dysphagia Symptom Questionnaire) score
timeFrame: Week 52
measure: 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
timeFrame: Week 52
measure: 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)
timeFrame: Week 52
measure: Total endoscopic remission of total EREFS score of 0 across all esophageal levels
timeFrame: Week 52
Other outcomes:
measure: Change from baseline in peak esophageal eosinophil count (EOS/HPF)
timeFrame: Week 24, Week 52
measure: Changes from baseline in PEESS Module at Week 24 (adolescents only).
timeFrame: Week 24, Week 52
measure: Change from baseline in EoE-HSS (Histologic scoring system) stage score
timeFrame: Week 52
measure: Change from baseline in EoE-HSS (Histologic scoring system) grade score
timeFrame: Week 52
measure: Serum tezepelumab concentration
timeFrame: Weeks 0, 4, 12, 24, and 52
measure: Anti-drug antibody
timeFrame: Weeks 0, 12, 24, and 52
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Study officials:
References: