We plan to do a multicentre, randomised study of netazepide and placebo (ratio 6:1) in 210 patients with CAG and multiple g-NETs in Europe, USA, and possibly China and Japan (Figure 13). Centres of Excellence of the European and North American Neuroendocrine Tumour Societies (ENETS and NANETS, respectively) have agreed to participate (Figure 14). The NET Patient Foundation and the Pernicious Anaemia Society, organisations with members who have g-NETs, have also agreed to support the study.
The European Medicines Agency has approved in principle a single pivotal study. An IND is in place, and an FDA end-of-phase 2 meeting is planned. The study is on schedule to start fourth quarter 2020 and to last 3 years.
Figure 13. Design of proposed study of netazepide in 210 patients
Figure 14. Centres with g-NETs patients in Europe, USA, China and Japan, and patient organisations
Patients with the rare Zollinger Ellison syndrome have a gastrin-secreting tumour called a gastrinoma that grows mainly in the pancreas or gut and causes hypergastrinaemia, growth of ECL cells, and in some patients, formation of g-NETs1. Up to 50% of those g-NETs become malignant, especially in the 20–30% of patients with the multiple endocrine neoplasia (MEN-1) gene. But, unlike CAG patients, patients with a gastrinoma have an intact stomach lining, which therefore responds to hypergastrinaemia by producing excessive acid and thereby severe ulcers. Netazepide blocks gastric acid production as well as ECL-cell growth, which makes it an ideal treatment for Zollinger Ellison syndrome. Therefore, we plan a separate clinical trial of netazepide in patients with Zollinger Ellison g-NETs.
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