Trial Outcomes & Findings for YF476 in Barrett's Esophagus (NCT NCT02597712)
NCT ID: NCT02597712
Last Updated: 2021-04-12
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
27 participants
Primary outcome timeframe
Baseline and Week 12
Results posted on
2021-04-12
Participant Flow
Three patients were enrolled but failed screening due to elevated lipase, prolonged QTc or being diagnosed with lymphoma.
Participant milestones
| Measure |
Treatment
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Overall Study
STARTED
|
13
|
11
|
|
Overall Study
COMPLETED
|
10
|
10
|
|
Overall Study
NOT COMPLETED
|
3
|
1
|
Reasons for withdrawal
| Measure |
Treatment
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Overall Study
Baseline biopsies showed indefinite for dysplasia
|
2
|
0
|
|
Overall Study
Baseline biopsies showed low grade dysplasia
|
1
|
0
|
|
Overall Study
Recurrent metastatic prostate cancer
|
0
|
1
|
Baseline Characteristics
YF476 in Barrett's Esophagus
Baseline characteristics by cohort
| Measure |
Treatment
n=13 Participants
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
n=11 Participants
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
Total
n=24 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
>=65 years
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
13 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
7 participants
n=5 Participants
|
5 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Ki67 expression
|
1539 cells/mm^2
STANDARD_DEVIATION 514 • n=5 Participants
|
1556 cells/mm^2
STANDARD_DEVIATION 622 • n=7 Participants
|
1548 cells/mm^2
STANDARD_DEVIATION 559 • n=5 Participants
|
|
Fasting serum gastrin concentration (marker of gastric acid suppression)
|
66.74 pmol/L
STANDARD_DEVIATION 41.736 • n=5 Participants
|
51.85 pmol/L
STANDARD_DEVIATION 29.104 • n=7 Participants
|
56.45 pmol/L
STANDARD_DEVIATION 35.997 • n=5 Participants
|
|
Fasting plasma CgA concentration (marker of ECL cell hyperplasia)
|
12.93 nmol/L
STANDARD_DEVIATION 17.210 • n=5 Participants
|
9.12 nmol/L
STANDARD_DEVIATION 4.98 • n=7 Participants
|
11.18 nmol/L
STANDARD_DEVIATION 13.00 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline and Week 12Population: 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.
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.
Outcome measures
| Measure |
Treatment
n=13 Participants
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
n=11 Participants
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Change in Ki67 Biomarker Expression
Baseline
|
1539 cells/mm^2
Standard Deviation 514
|
1556 cells/mm^2
Standard Deviation 622
|
|
Change in Ki67 Biomarker Expression
Week 12
|
1575 cells/mm^2
Standard Deviation 620.7
|
1864 cells/mm^2
Standard Deviation 640.3
|
SECONDARY outcome
Timeframe: Week 12Population: 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.
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.
Outcome measures
| Measure |
Treatment
n=10 Participants
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)
CCK2R, Week 12
|
-1.19 relative log-fold change
|
—
|
|
Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)
PTGS2, Week 12
|
0.31 relative log-fold change
|
—
|
|
Expression of Biomarkers Potentially Associated With Esophageal Adenocarcinoma (EAC)
DCLK1, Week 12
|
-0.34 relative log-fold change
|
—
|
SECONDARY outcome
Timeframe: Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)Population: 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.
Blood samples were taken to assess the effects of YF476 on fasting serum gastrin, a marker of gastric acid suppression
Outcome measures
| Measure |
Treatment
n=10 Participants
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
n=10 Participants
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Abundance of Biomarkers of Gastric Acid Suppression
Week 4
|
242.6 pmol/L
Standard Deviation 142.3
|
43.6 pmol/L
Standard Deviation 9.9
|
|
Abundance of Biomarkers of Gastric Acid Suppression
Week 6
|
103.3 pmol/L
Standard Deviation 89.9
|
63.9 pmol/L
Standard Deviation 32.2
|
|
Abundance of Biomarkers of Gastric Acid Suppression
Week 8
|
234.3 pmol/L
Standard Deviation 156.5
|
96.4 pmol/L
Standard Deviation 54.2
|
|
Abundance of Biomarkers of Gastric Acid Suppression
Week 12
|
146.8 pmol/L
Standard Deviation 112.8
|
49.2 pmol/L
Standard Deviation 20.4
|
|
Abundance of Biomarkers of Gastric Acid Suppression
Follow-up
|
94.9 pmol/L
Standard Deviation 78.8
|
64.7 pmol/L
Standard Deviation 37.7
|
SECONDARY outcome
Timeframe: Week 4, Week 6, Week 8, Week 12 and Follow-up (4 weeks after stopping YF476 treatment)Population: 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.
Blood samples were taken to assess the effects of YF476 on fasting plasma CgA, a marker of ECL cell hyperplasia
Outcome measures
| Measure |
Treatment
n=10 Participants
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
n=10 Participants
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Abundance of Biomarkers of ECL Cell Hyperplasia
Week 4
|
3.9 nmol/L
Standard Deviation 1.8
|
8.8 nmol/L
Standard Deviation 3.7
|
|
Abundance of Biomarkers of ECL Cell Hyperplasia
Week 6
|
1.8 nmol/L
Standard Deviation 0.9
|
16.9 nmol/L
Standard Deviation 9.8
|
|
Abundance of Biomarkers of ECL Cell Hyperplasia
Week 8
|
3.8 nmol/L
Standard Deviation 1.8
|
10.9 nmol/L
Standard Deviation 6.0
|
|
Abundance of Biomarkers of ECL Cell Hyperplasia
Week 12
|
2.9 nmol/L
Standard Deviation 2.5
|
10.6 nmol/L
Standard Deviation 7.4
|
|
Abundance of Biomarkers of ECL Cell Hyperplasia
Follow-up
|
19.8 nmol/L
Standard Deviation 26.1
|
11.9 nmol/L
Standard Deviation 7.2
|
Adverse Events
Treatment
Serious events: 1 serious events
Other events: 13 other events
Deaths: 0 deaths
YF476 Placebo
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Treatment
n=13 participants at risk
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
n=11 participants at risk
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Infections and infestations
Scrotal abscess
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
Other adverse events
| Measure |
Treatment
n=13 participants at risk
Patients will take 25 mg YF476 once daily for 12 weeks
YF476: gastrin receptor antagonist
|
YF476 Placebo
n=11 participants at risk
Patients will take matching placebo once daily for 12 weeks
YF476 placebo: placebo
|
|---|---|---|
|
Gastrointestinal disorders
Constipation
|
15.4%
2/13 • Number of events 2 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
15.4%
2/13 • Number of events 3 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Nausea
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Abdominal upper pain
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 2 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Gatrooesophageal reflux disease
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Mouth ulveration
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Nervous system disorders
Headache
|
23.1%
3/13 • Number of events 3 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
27.3%
3/11 • Number of events 3 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Nervous system disorders
Presyncope
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Nervous system disorders
Dizziness
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
18.2%
2/11 • Number of events 3 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Rhintis allergic
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Infections and infestations
Nasopharyngitis
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Infections and infestations
Rash pustular
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
18.2%
2/11 • Number of events 2 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
General disorders
Chest pain
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
General disorders
Fatigue
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
General disorders
Pyrexia
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Cardiac disorders
Bundle branch block right
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
7.7%
1/13 • Number of events 1 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
0.00%
0/11 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/13 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
9.1%
1/11 • Number of events 2 • 16 weeks
Any untoward medical occurrence in a study participant that does not necessarily have a causal relationship with the treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place