A Phase 2 interventional study of YF476 and Placebo in Barrett's Esophagus, sponsored by Columbia University. Completed at 2 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-23.
Sponsored by Columbia University · Phase 2, Interventional, and Prevention
The purpose of this study is to determine whether treatment with an experimental drug called YF476 in patients with Barrett's esophagus reduces the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.
The association between gastro-esophageal reflux disease (GERD) and cancer of the esophagus is well-established. Barrett's esophagus (BE) is a condition in which the lining of the part of the esophagus changes to look like small intestine, and this change occurs in the setting of GERD. Patients with BE are at increased risk for developing esophageal cancer. It is recommended that all patients with BE take medicines called proton pump inhibitors (PPIs), which greatly reduce the acid produced by the stomach, in the hopes of reducing the risk of esophageal cancer. However, by reducing the acid level in the stomach, levels of a hormone called gastrin are increased. There is laboratory data to suggest that gastrin may have effects that actually promote the development of cancer, including esophageal cancer. The investigators previously showed that BE patients with very high gastrin levels are more likely to have either advanced precancerous changes (also called high grade dysplasia) or cancer of the esophagus. As such, the obvious question is raised: does gastrin promote the development of cancer in BE? YF476 is a new drug that blocks the effects of gastrin. Trials in healthy subjects have demonstrated that the drug is safe and well-tolerated. The investigators therefore propose to conduct a randomized placebo-controlled trial of YF476 in patients with Barrett's esophagus. The primary hypothesis is that treatment with YF476 will reduce the expression of tissue markers that are associated with an increased risk of developing esophageal cancer.
310 studies on the registry are indexed under Barrett Esophagus; 64 are open to participants now.
This study's enrollment of 27 is below the median of 62 across 186 interventional studies indexed under Barrett Esophagus.
Browse Barrett Esophagus studies →Columbia University is the lead sponsor of 1,103 studies on the registry; 193 are open to participants now.
Of its 172 completed or terminated interventional studies of FDA-regulated products, 142 (83%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
YF476 (gastrin-receptor antagonist)
Drug: YF476
Placebo pill (identical in appearance to YF476 pills)
Drug: Placebo
25 mg: one capsule to be taken by mouth once daily for 12 weeks.
Also known as: Netazepide
Matching placebo: one capsule to be taken by mouth once daily for 12 weeks.
Also known as: Placebo Tablet
Mean Ki67 Expression
The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.
Time frame: Up to 3 months from baseline
Number of Participants That Experienced Change in Any Biomarker Expression
Participants with changes in gene expression were assessed by RNA-sequencing (i.e., sample has sufficient RNA for analysis) between baseline and up to 3 months are tallied.
Time frame: Up to 3 months from baseline
Number of Participants That Experienced Adverse Events
A measure of safety and tolerability. Participants with recorded adverse events were tallied. The events include any adverse events and/or severe adverse events.
Time frame: Up to 4 months from baseline
| Milestone | YF476 | Placebo |
|---|---|---|
| Started | 13 | 11 |
| Completed | 10 | 10 |
| Not completed | 3 | 1 |
| Withdrew: Physician decision | 0 | 1 |
| Withdrew: Baseline endoscopy showed low grade dysplasia or indefinite for dysplasia | 3 | 0 |
The study is designed to examine change in tissue Ki67 expression, a marker of cellular proliferation.
| cells/mm2 | YF476 | Placebo |
|---|---|---|
| Mean Ki67 Expression | 35.6 ± 620.7 | 307.8 ± 640.3 |
Participants with changes in gene expression were assessed by RNA-sequencing (i.e., sample has sufficient RNA for analysis) between baseline and up to 3 months are tallied.
| Participants | YF476 | Placebo |
|---|---|---|
| Number of Participants That Experienced Change in Any Biomarker Expression | 10 | 9 |
A measure of safety and tolerability. Participants with recorded adverse events were tallied. The events include any adverse events and/or severe adverse events.
| Participants | YF476 | Placebo |
|---|---|---|
| Serious Adverse Event | 1 | 0 |
| Any Adverse Event | 10 | 7 |
Collected over Throughout the course of treatment and up to four weeks after completion of the study drug course or placebo course - an average of 4 months.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| YF476 | 0/13 (0%) | 1/13 (7.7%) | 10/13 (76.9%) |
| Placebo | 0/11 (0%) | 0/11 (0%) | 7/11 (63.6%) |
| Event | YF476 | Placebo |
|---|---|---|
| Scrotal abscessReproductive system and breast disorders | 1/13 | 0/11 |
| Event | YF476 | Placebo |
|---|---|---|
| HeadacheNervous system disorders | 3/13 | 3/11 |
| DiarrheaGastrointestinal disorders | 3/13 | 1/11 |
| Abdominal painGastrointestinal disorders | 2/13 | 2/11 |
| NasopharyngitisRespiratory, thoracic and mediastinal disorders | 2/13 | 2/11 |
| CoughRespiratory, thoracic and mediastinal disorders | 0/13 | 2/11 |
| MyalgiaMusculoskeletal and connective tissue disorders | 0/13 | 2/11 |
| ConstipationGastrointestinal disorders | 2/13 | 1/11 |
| RashSkin and subcutaneous tissue disorders | 2/13 | 1/11 |
| DizzinessNervous system disorders | 2/13 | 1/11 |
| NauseaGastrointestinal disorders | 1/13 | 1/11 |
| Age, Continuous(years) | YF476 | Placebo | Total |
|---|---|---|---|
| Mean | 64.4 ± 7.2 | 68.6 ± 6.6 | 66.3 ± 7.1 |
| Sex: Female, Male(Participants) | YF476 | Placebo | Total |
|---|---|---|---|
| Female | 2 | 1 | 3 |
| Male | 11 | 10 | 21 |
| Race/Ethnicity, Customized(Participants) | YF476 | Placebo | Total |
|---|---|---|---|
| Race, white | 13 | 11 | 24 |
| BMI(kg/m2) | YF476 | Placebo | Total |
|---|---|---|---|
| Mean | 28.9 ± 4.7 | 26.7 ± 3.1 | 27.9 ± 4.1 |
| Waist circumference(cm) | YF476 | Placebo | Total |
|---|---|---|---|
| Mean | 95.7 ± 17.8 | 98.1 ± 10.9 | 96.8 ± 14.8 |
| Current smoker(Participants) | YF476 | Placebo | Total |
|---|---|---|---|
| Count of participants | 0 | 0 | 0 |
| Proton Pump Inhibitor (PPI) frequency(Participants) | YF476 | Placebo | Total |
|---|---|---|---|
| Once daily | 8 | 6 | 14 |
| Twice daily | 5 | 5 | 10 |
| Aspirin Use(Participants) | YF476 | Placebo | Total |
|---|---|---|---|
| Count of participants | 3 | 2 | 5 |
4 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
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