728-P: Experience with Teplizumab in the PROTECT Type 1 Diabetes (T1D) Study during the COVID-19 Pandemic

Background & aims: Teplizumab is a humanized anti-CD3 monoclonal antibody approved to delay Stage 3 T1D onset in individuals ≥8 years with Stage 2 T1D. The Phase 3 PROTECT study (NCT03875729) was conducted during the COVID-19 pandemic. COVID 19 incidence was similar between the teplizumab (22.6%) and placebo (PBO; 23.4%) groups. No participants with an AE of COVID-19 were hospitalized or received antiviral treatment. Here we report our experience of an immunomodulatory therapy during a pandemic. Methods: Participants aged 8-17 years, diagnosed ≤6 weeks with Stage 3 T1D, were randomized 2:1 to two 12-day courses of teplizumab or PBO, administered 6 months apart. Due to the COVID-19 pandemic, modified dosing was permitted, allowing for the 2nd course to be given at 12 months, instead of 6 months. COVID-19 testing was required before each course. Results: Rates of overall infections were similar (65.9% vs 63.1%) in the teplizumab and PBO groups, respectively. The rate of Grade ≥3 infections was similar between treatment groups; 1 (0.5%) participant had a Grade ≥3 infection in the teplizumab group (cellulitis), compared with 2 (1.8%) participants in the PBO group (cellulitis and gastroenteritis; n=1 each). No serious AEs of infection were reported for participants in the teplizumab group. Few participants experienced AEs of infection that led to study drug discontinuation: 1 (0.5%) participant in the teplizumab (COVID-19) and 2 (1.8%) participants experienced 3 AEs in the PBO group (COVID-19, cellulitis, and device-related bacteremia). COVID-19-related protocol deviations were comparable in both groups and were mainly related to study visit or laboratory testing. Conclusions: Incidence of infections, and rates of study drug discontinuation related to AEs of infection, were similar for teplizumab and PBO. Notably, COVID-19-related AEs were not increased by teplizumab treatment, supporting the concept that teplizumab is immunomodulatory, rather than immunosuppressive, therapy.