YF476 in Barrett's Esophagus

NCT02597712 | Completed Phase 2 Results

• 1 other identifier: T-016
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Barrett's Esophagus

Keywords

acid reflux; intragastric pH; gastrin; hypergastrinemia

Outcome Measures

Primary Outcomes (1)

• Change in Ki67 Biomarker Expression

  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.

  Baseline and Week 12

Secondary Outcomes (3)

• Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)

  Week 12

• Abundance of Biomarkers of Gastric Acid Suppression

  Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)

• Abundance of Biomarkers of ECL Cell Hyperplasia

  Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)

Study Arms (2)

Treatment

EXPERIMENTAL

Patients will take 25 mg YF476 once daily for 12 weeks

Drug: YF476

YF476 Placebo

PLACEBO COMPARATOR

Patients will take matching placebo once daily for 12 weeks

Drug: YF476 placebo

Interventions

YF476 DRUG

gastrin receptor antagonist

Also known as: netazepide

Treatment

YF476 placebo DRUG

placebo

Also known as: netazepide placebo

YF476 Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged \>18 years, with histologically confirmed diagnosis of Barrett's esophagus (BE) without dysplasia. A prior endoscopy with biopsies read as indefinite for dysplasia is permitted if biopsies from the most recent endoscopy prior to study entry demonstrated BE without dysplasia.
• Minimum of 1 cm circumferential Barrett's mucosa on endoscopy or at least 2 cm maximal contiguous extent of Barrett's mucosa, as measured from the top of the gastric folds to the squamocolumnar junction (Prague criteria C\>1, any M or any C, M\>2).
• Proton pump inhibitor use at least once daily, for at least 12 months prior to enrolment, and stable dose of PPI for the 3 months before enrolment. Any PPI, dose, and frequency allowable.
• ECOG performance status \<2 and Karnofsky \>60%
• Normal organ and marrow function, defined as white blood cells \>3 x 10e9, absolute neutrophil count \>1.5 x 10e9, platelets \>100 x 10e9, creatinine \<1.5 mg/dL, total bilirubin \<1.5 mg/dL, AST \<100 U/L, ALT \<100 U/L.
• Use of adequate contraception during the study, as follows;
• Post-menopausal women must have had their last menstrual period at least 1 year ago.
• Pre-menopausal women, who are sexually-active, must have had a hysterectomy or bilateral oophorectomy; or must use an intrauterine device (IUD), or spermicide with a diaphragm, cap or condom. Streroid contraceptives such as 'the pill' are not allowed unless in combination with one of the aforementioned barrier contraceptive methods.
• Men must use a condom and spermicide.
• Willingness to comply with all treatment and follow-up procedures.
• Ability to understand and the willingness to sign a written informed consent document.
• Up to date with all age-appropriate cancer screening tests, as per American Cancer Society guidelines, (Columbia University only), and no cancer screening tests planned for the next 21 weeks.

You may not qualify if:

• Histologically confirmed BE with high-grade dysplasia.
• Histologically confirmed diagnosis of invasive carcinoma of the esophagus.
• Histologically confirmed BE with low-grade dysplasia that has been diagnosed by at least 2 expert gastrointestinal pathologists.
• Prior endoscopic therapy for BE.
• Any history of esophageal or gastric surgery.
• History of atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome.
• Participation in a trial of an IMP within the previous 28 days.
• Prolonged QTc interval \>450 msec.
• History of allergic reactions attributed to compounds of similar chemical composition of YF476.
• History of baseline findings of:
• diabetes mellitus requiring insulin therapy
• pancreatitis (baseline amylase and/or lipase \>2.0 x ULN)
• hepatitis B, hepatitis C or HIV
• malabsorption syndrome or inability to swallow or retain oral medicine
• major surgery \<28 days prior to enrolment

Sponsors & Collaborators

• Trio Medicines Ltd.: lead
• Columbia University: collaborator
• University of Cambridge: collaborator

Study Sites (2)

Columbia University, Division of Digestive & Liver Diseases

New York, New York, 10032, United States

Location

MRC Cancer Unit, University of Cambridge

Cambridge, Cambridgeshire, CB2 0XZ, United Kingdom

Location

MeSH Terms

Conditions

Barrett Esophagus; Gastroesophageal Reflux

Interventions

YF 476

Condition Hierarchy (Ancestors)

Precancerous Conditions; Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Esophageal Motility Disorders; Deglutition Disorders

Results Point of Contact

• Title: Dr Malcolm Boyce
• Organization: Trio Medicines Ltd

mboyce@triomedicines.com

+44 20 8961 4130

Study Officials

• Julian A Abrams, MD MS

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: November 5, 2015
• Study Start: May 15, 2013
• Primary Completion: November 28, 2017
• Study Completion: December 27, 2017
• Last Updated: April 12, 2021
• Results First Posted: April 12, 2021

Record last verified: 2021-04

Locations

GB (1); US (1)