Study design
STAGGERED
The study consisted of two parts. In the open-label Phase 1b study, two single ascending doses (low and high dose: one or three capsules twice daily, respectively) of AG019 monotherapy were administered in adults and adolescents. Participants were enrolled in four sequential AG019 monotherapy cohorts (low-dose adult, high-dose adult, low-dose adolescent, high-dose adolescent) following a multi-step enrolment plan (electronic supplementary material [ESM] Fig. In the randomised, double-blind Phase 2a study, adult and adolescent participants were enrolled in the AG019/teplizumab combination therapy cohort. Three AG019 (or placebo) capsules were administered twice daily for 8 weeks, and teplizumab or placebo infusions were administered daily for the first 12 days. In each combination therapy cohort, the first two participants were enrolled in a staggered way as a safety measure and received active treatment (AG019 plus teplizumab) in an open-label fashion. The remaining ten participants were randomised (4:1) to active treatment or placebo in a double-blind fashion. Participants were randomised and started treatment on day 1 and were followed for 12 months (8 weeks of treatment and 10 months of post-treatment follow-up).