Memorandum
Recruitment has begun for the Primary Oral Insulin Trial (POInT), the Global Platform for Prevention of Autoimmune Diseases’ (GPPAD) inaugural, phase 2b study (n=1,040) to prevent or delay type 1 diabetes, according to a recent Diabetes UK announcement. The University of Oxford hopes to screen 30,000 babies over the next three years to identify ≥300 who are at high genetic risk for type 1 and eligible for the study. POInT is currently scheduled to complete in January 2025.
Overall, the trial aims to screen >300,000 pregnant mothers and newborns across the five GPPAD countries (Germany, UK, Belgium, Poland, and Sweden) to identify 3,000 at-risk children and enroll 1,040 participants in a trial comparing oral insulin to placebo.
The primary endpoints of POInT are (i) development of multiple autoantibodies (≥two) and (ii) development of diabetes. According to Diabetes UK and ClinicalTrials.gov, children will be given oral insulin or placebo until the age of three (29 to 32 months total, starting at four to seven months old), then followed for up to 7.5 years. Oral insulin dosage will start at 7.5 mg and escalate to 22.5 mg, then 67.5 mg.
As a reminder, last December, the Helmsley Charitable Trust awarded five grants totaling $52 million to the brand-new GPPAD. This was the largest investment HCT has ever made in a type 1 diabetes program.
Oral insulin for type 1 prevention has a storied past. At ADA 2017, results from TrialNet’s oral insulin study were presented: The study failed to meet its primary endpoint and, despite some encouraging subgroup results, oral insulin gave largely neutral results. However, as HCT’s Dr. Gina Agiostratidou has explained to us, POInT is investigating a higher dose of oral insulin and intervening earlier in the natural history of disease. TrialNet enrolled people who already had autoimmunity, while POInT is a primary prevention trial. As such, the field seems to have some renewed optimism in oral insulin for prevention, and POInT would be game-changing should it read out positively.
--by Peter Rentzepis, Martin Kurian, Ann Carracher, Kelly Close