- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02597712
YF476 in Barrett's Esophagus
April 9, 2021 updated by: Trio Medicines Ltd.
Randomized, Placebo-controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
27
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Cambridgeshire
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Cambridge, Cambridgeshire, United Kingdom, CB2 0XZ
- MRC Cancer Unit, University of Cambridge
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New York
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New York, New York, United States, 10032
- Columbia University, Division of Digestive & Liver Diseases
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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
- ECOG performance status >2
- another cancer within 3 years except for basal carcinoma of the skin or cervical carcinoma in-situ
- also, any clinically significant and uncontrolled major morbidity including but not limited to: serious cardiac disease (unstable angina, s/p myocardial infarction <1 month); respiratory disease (advanced COPD or pulmonary fibrosis); uncontrolled hypertension; active systemic infection; or psychiatric illness/social situations that would limit compliance with study requirements.
- Certain medicines and herbal remedies taken during the 7 days before the start of the study drug.
- A history of cancer >3 years from the time of enrolment, and the patient is not up to date with surveillance for that cancer (based on the American Cancer Society guidelines, Columbia University only), has evidence of cancer at the time of enrolment, or has surveillance tests planned within 21 weeks after enrolment.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Treatment
Patients will take 25 mg YF476 once daily for 12 weeks
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gastrin receptor antagonist
Other Names:
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Placebo Comparator: YF476 Placebo
Patients will take matching placebo once daily for 12 weeks
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placebo
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change in Ki67 Biomarker Expression
Time Frame: Baseline and Week 12
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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.
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Baseline and Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)
Time Frame: Week 12
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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.
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Week 12
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Abundance of Biomarkers of Gastric Acid Suppression
Time Frame: Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)
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Blood samples were taken to assess the effects of YF476 on fasting serum gastrin, a marker of gastric acid suppression
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Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)
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Abundance of Biomarkers of ECL Cell Hyperplasia
Time Frame: Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)
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Blood samples were taken to assess the effects of YF476 on fasting plasma CgA, a marker of ECL cell hyperplasia
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Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Julian A Abrams, MD MS, Columbia University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
May 15, 2013
Primary Completion (Actual)
November 28, 2017
Study Completion (Actual)
December 27, 2017
Study Registration Dates
First Submitted
June 3, 2015
First Submitted That Met QC Criteria
November 4, 2015
First Posted (Estimate)
November 5, 2015
Study Record Updates
Last Update Posted (Actual)
April 12, 2021
Last Update Submitted That Met QC Criteria
April 9, 2021
Last Verified
April 1, 2021
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- T-016
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Barrett's Esophagus
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Northwell HealthMayo Clinic; NinePoint MedicalCompletedBarrett's Esophagus Without Dysplasia | Barrett's Esophagus With Dysplasia | Barrett's Esophagus With Low Grade Dysplasia | Barrett's Esophagus With High Grade Dysplasia | Barrett's Esophagus With Dysplasia, UnspecifiedUnited States
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Case Comprehensive Cancer CenterCompletedShort Segment Barrett's Esophagus | Long Segment Barrett's EsophagusUnited States
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The Guthrie ClinicActive, not recruiting
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Interscope, Inc.RecruitingBarrett's Esophagus With DysplasiaUnited States, Sweden, United Kingdom
-
Mayo ClinicCompletedBarrett's Esophagus With DysplasiaUnited States
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Massachusetts General HospitalEnrolling by invitationBarrett Esophagus | Barrett's Esophagus Without Dysplasia | Barretts Esophagus With DysplasiaUnited States
-
Lucid Diagnostics, Inc.CompletedBarrett Esophagus | Esophageal Adenocarcinoma | Barrett's Esophagus Without Dysplasia | Barretts Esophagus With DysplasiaUnited States, Spain
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University of CambridgeUniversity of NottinghamRecruitingBarrett's OesophagusUnited Kingdom
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Johns Hopkins UniversityAmerican Society for Gastrointestinal Endoscopy; Pentax Medical CorporationCompletedBarrett's Esophagus, Esophageal Intraepithelial NeoplasiaUnited States, Germany
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Mayo ClinicFred Hutchinson Cancer CenterCompletedBarrett's Esophagus With High Grade Dsyplasia | Early Esophageal CancerUnited States
Clinical Trials on YF476
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Trio Medicines Ltd.Royal Liverpool University HospitalCompletedHypergastrinaemia | Chronic Atrophic Gastritis | Type I Gastric CarcinoidsUnited Kingdom
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Trio Medicines Ltd.Norwegian University of Science and TechnologyTerminatedChronic Atrophic Gastritis | Hypergastrinemia | Type I Gastric CarcinoidsNorway
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Trio Medicines Ltd.James Black FoundationCompleted
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Trio Medicines Ltd.Ferring PharmaceuticalsCompletedReflux OesophagitisUnited Kingdom
-
Trio Medicines Ltd.Ferring PharmaceuticalsCompletedReflux OesophagitisUnited Kingdom
-
Trio Medicines Ltd.National Institutes of Health (NIH)TerminatedZollinger-Ellison Syndrome
-
Trio Medicines Ltd.James Black FoundationCompleted
-
Columbia UniversityTrio Medicines Ltd.CompletedBarrett's EsophagusUnited States, United Kingdom
-
Trio Medicines Ltd.CompletedDyspepsia | ECL-cell Hyperplasia | Parietal-cell Hyperplasia | Rebound Hyperacidity
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Trio Medicines Ltd.Completed