YF476 and Type II Gastric Carcinoids

NCT02454075 | Terminated Phase 2 Results

• 2 other identifiers: T-01011-DK-0114
• Study Type: interventional
• Target: 3
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Zollinger-Ellison Syndrome

Keywords

YF476; netazepide; gastric carcinoids; Zollinger-Ellison syndrome

Outcome Measures

Primary Outcomes (2)

• 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.

  Week 12 visit

• A Reduction of 25% in the Gastric ECL Cell Density.

  A reduction of 25% in the gastric ECL cell density.

  Week 12 visit

Secondary Outcomes (9)

• Improvement in Histological Grade of Gastric Carcinoids/ECL Cell Hyperplasia Defined by Physical Measurements Taken During Endoscopy

  Week 12 visit

• Level of Chromogranin A (CgA) Biomarkers Measured in Blood Samples

  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

  Week 2 visit (baseline) and Week 6 visit

• Decrease in ECL Cell-specific Products Assessed by Quantitative PCR

  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

  Week 2 visit (baseline), Week 6 visit, Week 12 visit, Follow-up (12 weeks after stopping YF476 treatment)

Study Arms (1)

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.

Drug: YF476

Interventions

YF476 DRUG

Gastrin receptor antagonist

Also known as: Netazepide

Eligible patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• Trio Medicines Ltd.: lead
• National Institutes of Health (NIH): collaborator

MeSH Terms

Conditions

Zollinger-Ellison Syndrome

Interventions

YF 476

Condition Hierarchy (Ancestors)

Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases

Results Point of Contact

• Title: Dr Malcolm Boyce
• Organization: Trio Medicines

mboyce@hmrlondon.com

020 8961 4130

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2015
• First Posted: May 27, 2015
• Study Start: April 11, 2011
• Primary Completion: June 22, 2012
• Study Completion: June 22, 2012
• Last Updated: January 29, 2021
• Results First Posted: January 29, 2021

Record last verified: 2021-01