Digestive System Diseases

All Conditions

Neoplasms

Gastroesophageal Reflux

Barrett Esophagus

Precancerous Conditions

Esophageal Diseases

Gastrointestinal Diseases

All Drugs and Chemicals

Gastrins

Patients will take 25 mg YF476 once daily for 12 weeks

Patients will take matching placebo once daily for 12 weeks

YF476

YF476 placebo

Julian A Abrams, MD MS

A phase 2, randomised, double-blind, out-patient trial to determine if YF476 is a safe and effective treatment in patients with Barrett's esophagus.

YF476 in Barrett's Esophagus

Randomized, Placebo-controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus

Esophagogastroduodenoscopy (EGD) was performed to enable taking biopsies for assessment of Ki67 expression, a marker of cellular proliferation. Ki67 expression was assessed by immunohistochemistry and calculating the number of Ki67 positive cells per mm\^2 of Barrett's epithelium.

Blood samples were taken for assay of biomarkers associated with esophageal adenocarcinoma. Changes in biomarker expression were derived from RNA-Sequencing and calculated as log-fold change comparing the treatment group to the placebo group. The nature of how results are derived by RNA-sequencing means summary statistics cannot be generated individually for each arm and a value has not been calculated for each individual participant. Therefore, results are reported as the relative change in biomarker expression in the treatment arm compared to the placebo arm.

Blood samples were taken to assess the effects of YF476 on fasting serum gastrin, a marker of gastric acid suppression

Blood samples were taken to assess the effects of YF476 on fasting plasma CgA, a marker of ECL cell hyperplasia

Columbia University

University of Cambridge

Trio Medicines Ltd.

Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment

Patients will take 25 mg YF476 once daily for 12 weeks

YF476: gastrin receptor antagonist

Treatment

Patients will take matching placebo once daily for 12 weeks

YF476 placebo: placebo

YF476 Placebo

Total

Age, Categorical

Sex: Female, Male

Race (NIH/OMB)

United States

United Kingdom

Region of Enrollment

Ki67 expression

Fasting serum gastrin concentration (marker of gastric acid suppression)

Fasting plasma CgA concentration (marker of ECL cell hyperplasia)

Dr Malcolm Boyce

Baseline

Week 12

3 patients in the treatment arm and 1 patient in the placebo arm were withdrawn from the study due to reasons unrelated to the treatment. Therefore, Week 12 data show results from 10 patients per arm.

Change in Ki67 Biomarker Expression

CCK2R, Week 12

PTGS2, Week 12

DCLK1, Week 12

3 patients in the treatment arm were withdrawn from the study due to reasons unrelated to the treatment. Therefore, results are reported for 10 patients.

Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)

Week 4

Week 6

Week 8

Follow-up

After 6 patients (3 per treatment) had their Week 4 and 8 visits, the protocol was amended so that those visits were replaced by a single visit at Week 6 in order to reduce the total number of visits.

Spots Global Cancer Trial Database for intragastric ph