Zollinger-Ellison SyndromePhase 2NCT02454075
YF476 and Type II Gastric Carcinoids
A Phase 2 study testing YF476 in people with Zollinger-Ellison Syndrome, run by Trio Medicines Ltd..
Trial summary
This study will evaluate whether treatment with YF476 is safe and effective in reducing the size of type II gastric carcinoid tumours, or limiting the abnormal growth of gastric ECL cells, in patients with Zollinger-Ellison syndrome. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Zollinger-Ellison Syndrome
- What is being tested?
- YF476
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- No sites listed yet
- Study dates
- 11 Apr 2011to 22 Jun 2012
- 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
- Men; post-menopausal women; pre-menopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy; or pre-menopausal women using one of the allowed methods of contraception: condom and spermicide or intra-uterine device.
- Patients with serum gastrin >250 pg/mL.
- Hepatic function: AST and ALT ≤2.0 x ULN; total bilirubin ≤1.0 x ULN.
- Renal function: serum creatinine <1.0 x ULN.
- Haematologic function: Hb ≥10.0 g/dL; WBC ≥3.5 x 10e9 /L; ANC ≥1.5 x 10e9 /L; platelets ≥100 x 10e9 /L.
- Coagulation parameters: INR or PT ≤1.0 x ULN; PTT ≤1.0 x ULN.
- Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire trial.
- Willingness to give fully-informed, written consent.
Who cannot join
- Patients under 18 years.
- Women who are pregnant, lactating or using a steroid contraceptive.
- Prior gastric resection or bypass.
- Planned gastrinoma resection during the study period.
- Patients on somatostatin analogues, except for those on therapy for >6 months with stable or worsening carcinoids.
- Inability to tolerate endoscopy, or refusal of endoscopy.
Show all 19Show fewer
- Physical findings, ECG (especially prolonged QTc interval >450 msec), or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
- Certain medicines and herbal remedies taken during the 7 days before visit 2.
- Participation in a trial of an IMP within the previous 28 days.
- Presence of drug or alcohol abuse.
- History or baseline findings of:
- type 1 diabetes mellitus;
- pancreatitis (baseline amylase and/or >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; or
- 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; or active systemic infection.
About this study
Official title: A Pilot Trial of YF476, a Gastrin Antagonist, in Patients With Type II Gastric Carcinoids Associated With Zollinger-Ellison Syndrome
This study will evaluate whether treatment with YF476 is safe and effective in reducing the size of type II gastric carcinoid tumours, or limiting the abnormal growth of gastric ECL cells, in patients with Zollinger-Ellison syndrome.
- Conditions
- Zollinger-Ellison Syndrome
- Being tested
- YF476
- Keywords
- YF476, netazepide, gastric carcinoids, Zollinger-Ellison syndrome
- Medical subject headings
- Zollinger-Ellison Syndrome
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
| Study group | Role | What they receive |
|---|---|---|
| Eligible patients | Experimental | The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia. Receives: Drug: YF476 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids. For each participant, three gastric carcinoids were identified and measured at baseline. The same gastric carcinoids were then measured at the Week 12 visit and the percentage difference in size from baseline calculated. The mean percentage change of the three gastric carcinoids per participant is recorded.
Measured: Week 12 visit
A Reduction of 25% in the Gastric ECL Cell Density.
A reduction of 25% in the gastric ECL cell density.
Measured: Week 12 visit
Secondary outcomes (9)
Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Reduction in the histological grade of the carcinoids/hyperplasia when compared to baseline.
Measured: Week 12 visit
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples
The level of a key biomarker chromogranin A (CgA) that is circulating in the blood was measured.
Measured: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
- Volume of aspirate (mL)
- Acid in aspirate (mEq)
- Acid output (mEq)
Measured: Week 2 visit (baseline) and Week 6 visit
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR
Assessed by quantitative PCR.
Measured: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument
Assessed by the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) instrument. Patients assessed a total of 10 symptoms on a scale of 0-5 where: 0 = no symptoms; 1 = symptoms noticeable, but not bothersome; 2 = symptoms noticeable and bothersome, but not every day; 3 = symptoms bothersome everyday; 4 = symptoms affect daily activities; and 5 = symptoms are incapacitating (unable to do daily activities). The total score was summed and reported. The maximum obtainable total score was 50 and minimum obtainable total score was 0, with higher scores indicating a worse outcome and lower scores indicating a better outcome.
Measured: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Safety and Tolerability
Assessed by monitoring adverse events reported by patients
Measured: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Circulating Plasma Concentration of Gastrin
The level of gastrin biomarkers circulating in the blood was measured.
Measured: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
- Volume of aspirate (mL)
- Acid in aspirate (mEq)
- Acid output (mEq)
Measured: Week 2 visit (baseline) and Week 6 visit
Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output
Assessed by changes in drug-controlled gastric acid analysis. A nasogastric tube (NGT) was placed through one nare and into the stomach. Gastric secretions were suctioned and discarded at T = 0 and then aspirated for 1 h in 15 min increments to measure the control acid output. Patients who could not tolerate NGT placement had endoscopic gastric analysis (EGA) performed during upper endoscopy. During EGA, a single 10 - 15 min collection was aspirated under direct visualization. Patients 01 and 02 had acid measured via NGT, whereas Patient 03 had acid measured via EGA. At the Week 2 visit, the baseline acid control was measured. At the Week 6 visit, the acid control was measured after a dose of netazepide. Results are provided for three acid control measures:
- Volume of aspirate (mL)
- Acid in aspirate (mEq)
- Acid output (mEq)
Measured: Week 2 visit (baseline) and Week 6 visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2015 (estimated)
- Study start11 Apr 2011
- Primary completion22 Jun 2012
- Study completion22 Jun 2012
Why it stopped: Poor recruitment
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 Zollinger-Ellison SyndromeStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trio Medicines Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02454075
- Sponsor's protocol ID
- T-010
- Other IDs
- 11-DK-0114
- Status last verified
- Jan 2021
- First submitted
- 13 May 2015
- Last updated
- 29 Jan 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 29 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of YF476, a Gastrin Antagonist, in Patients With Type II Gastric Carcinoids Associated With Zollinger-Ellison Syndrome
- ClinicalTrials.gov ID
- NCT02454075
- Acronym / sponsor ID
- T-010
- Conditions
- Zollinger-Ellison Syndrome
- Keywords
- YF476, netazepide, gastric carcinoids, Zollinger-Ellison syndrome
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Poor recruitment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Trio Medicines Ltd.Industry (pharma, biotech, devices)
- Collaborators
- National Institutes of Health (NIH)
- Study start
- 11 Apr 2011 (actual)
- Primary completion
- 22 Jun 2012 (actual)
- Study completion
- 22 Jun 2012 (actual)
- First posted
- 27 May 2015 (estimated)
- Results
- Posted 29 Jan 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate whether treatment with YF476 is safe and effective in reducing the size of type II gastric carcinoid tumours, or limiting the abnormal growth of gastric ECL cells, in patients with Zollinger-Ellison syndrome.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eligible patients | Experimental | Drug: YF476The dose will be 100 mg YF476 once daily. When 6 patients have completed 12 weeks' treatment with that dose, it may be increased to 150 or 200 mg once daily. Patients will have type II gastric carcinoids and/or ECL cell hyperplasia/dysplasia. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men; post-menopausal women; pre-menopausal women who have been sterilised by tubal ligation, hysterectomy or bilateral oophorectomy; or pre-menopausal women using one of the allowed methods of contraception: condom and spermicide or intra-uterine device.
- Patients with serum gastrin >250 pg/mL.
- Hepatic function: AST and ALT ≤2.0 x ULN; total bilirubin ≤1.0 x ULN.
- Renal function: serum creatinine <1.0 x ULN.
- Haematologic function: Hb ≥10.0 g/dL; WBC ≥3.5 x 10e9 /L; ANC ≥1.5 x 10e9 /L; platelets ≥100 x 10e9 /L.
Key exclusion criteria (19 listed)
- Patients under 18 years.
- Women who are pregnant, lactating or using a steroid contraceptive.
- Prior gastric resection or bypass.
- Planned gastrinoma resection during the study period.
- Patients on somatostatin analogues, except for those on therapy for >6 months with stable or worsening carcinoids.
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 | Eligible patients |
Primary outcome
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Time frame: Week 12 visit
Regression is defined as a 25% reduction in the size / number of endoscopically evident type II gastric carcinoids. For each participant, three gastric carcinoids were identified and measured at baseline. The same gastric carcinoids were then measured at the Week 12 visit and the percentage difference in size from baseline calculated. The mean percentage change of the three gastric carcinoids per participant is recorded.
A Reduction of 25% in the Gastric ECL Cell Density.
Time frame: Week 12 visit
A reduction of 25% in the gastric ECL cell density.
9 secondary outcomes
Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy
Time frame: Week 12 visit
Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples
Time frame: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Acid Control Study 1, Control of Gastric Acid Secretion Assessed by Changes in Drug-controlled Gastric Acid Analysis, Volume of Gastric Aspirate
Time frame: Week 2 visit (baseline) and Week 6 visit
Decrease in ECL Cell-specific Products Assessed by Quantitative PCR
Time frame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Improvement in Reflux/Dyspepsia Symptoms Using the Gastroesophageal Reflux Disease Health Related Quality of Life (GERD-HRQL) Instrument
Time frame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Safety and Tolerability
Time frame: Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Circulating Plasma Concentration of Gastrin
Time frame: Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)
Acid Control Study 2, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Content in Gastric Aspirate
Time frame: Week 2 visit (baseline) and Week 6 visit
Acid Control Study 3, Control of Gastric Acid Secretion Assess by Changes in Drug-controlled Gastric Acid Analysis: Acid Output
Time frame: Week 2 visit (baseline) and Week 6 visit
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Zollinger-Ellison Syndrome
Active, not recruitingObservational study
DOTATOC PET/CT for Imaging NET Patients
Neuroendocrine Tumors, Insulinoma
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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing YF476 in people with Zollinger-Ellison Syndrome, run by Trio Medicines Ltd..
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 8 inclusion and 19 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: stopped early, as of the sponsor's last update on 29 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 29 Jan 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?
Regression of Gastric Carcinoids and/or ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy (time frame: Week 12 visit). The study lists 2 primary outcomes in all. 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 29 Jan 2021.