Barrett's EsophagusPhase 2NCT02597712
YF476 in Barrett's Esophagus
A Phase 2 study testing YF476 in people with Barrett's Esophagus, run by Trio Medicines Ltd. at 2 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Barrett's Esophagus
- What is being tested?
- YF476
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 May 2013to 27 Dec 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
United States1 site
Columbia University, Division of Digestive & Liver Diseases
New York, New York, 10032
United Kingdom1 site
MRC Cancer Unit, University of Cambridge
Cambridge, Cambridgeshire, CB2 0XZ
About this study
Official title: 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.
- Conditions
- Barrett's Esophagus
- Being tested
- YF476, YF476 placebo
- Keywords
- acid reflux, intragastric pH, gastrin, hypergastrinemia
- Medical subject headings
- Barrett Esophagus, Gastroesophageal Reflux
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YF476Drug
Also called netazepide
gastrin receptor antagonist
YF476 placeboDrug
Also called netazepide placebo
placebo
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Patients will take 25 mg YF476 once daily for 12 weeks Receives: Drug: YF476 |
| YF476 Placebo | Placebo comparator | Patients will take matching placebo once daily for 12 weeks Receives: Drug: YF476 placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and Week 12
Secondary outcomes (3)
Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)
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.
Measured: Week 12
Abundance of Biomarkers of Gastric Acid Suppression
Blood samples were taken to assess the effects of YF476 on fasting serum gastrin, a marker of gastric acid suppression
Measured: Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)
Abundance of Biomarkers of ECL Cell Hyperplasia
Blood samples were taken to assess the effects of YF476 on fasting plasma CgA, a marker of ECL cell hyperplasia
Measured: Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2015 (estimated)
- Study start15 May 2013
- Primary completion28 Nov 2017
- Study completion27 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Barrett's EsophagusStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trio Medicines Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Columbia University, University of Cambridge
- Responsible party
- Sponsor
- Investigators
- Julian A Abrams, MD MS, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02597712
- Sponsor's protocol ID
- T-016
- Status last verified
- Apr 2021
- First submitted
- 3 Jun 2015
- Last updated
- 12 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-controlled Trial of YF476, a Gastrin Receptor Antagonist, in Barrett's Esophagus
- ClinicalTrials.gov ID
- NCT02597712
- Acronym / sponsor ID
- T-016
- Conditions
- Barrett's Esophagus
- Keywords
- acid reflux, intragastric pH, gastrin, hypergastrinemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Trio Medicines Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Columbia University, University of Cambridge
- Study start
- 15 May 2013 (actual)
- Primary completion
- 28 Nov 2017 (actual)
- Study completion
- 27 Dec 2017 (actual)
- First posted
- 5 Nov 2015 (estimated)
- Results
- Posted 12 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: YF476Patients will take 25 mg YF476 once daily for 12 weeks |
| YF476 Placebo | Placebo comparator | Drug: YF476 placeboPatients will take matching placebo once daily for 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YF476Also: netazepidegastrin receptor antagonist | Drug | Treatment |
| YF476 placeboAlso: netazepide placeboplacebo | Drug | YF476 Placebo |
Primary outcome
Change in Ki67 Biomarker Expression
Time frame: Baseline and Week 12
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.
3 secondary outcomes
Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)
Time frame: Week 12
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Barrett Esophagus
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julian A Abrams, MD MS principal investigator
Columbia University
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing YF476 in people with Barrett's Esophagus, run by Trio Medicines Ltd. at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Ki67 Biomarker Expression (time frame: Baseline and Week 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2021.