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.

Disclosure

S.E. Gitelman: Advisory Panel; Abata Therapeutics, Avotres Inc., Genentech, Inc., GentiBio, SAB Biotherapeutics, Inc., Sanofi. K.C. Herold: Consultant; Sanofi. K.M. Simmons: Advisory Panel; Provention Bio, Inc. Consultant; Provention Bio, Inc. Research Support; Provention Bio, Inc., Novartis AG. Consultant; Medtronic. Z. Sumnik: None. L. Knecht: Employee; Sanofi, Provention Bio, Inc. E. Niemoeller: Employee; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Sanofi. W. Tian: Employee; Sanofi. G.M. Comer: Consultant; Provention Bio, Inc., Sanofi. D.E. Miller: Employee; Provention Bio, Inc., Sanofi. E.L. Ramos: None.

Funding

Provention Bio, a Sanofi company

© 2024 by the American Diabetes Association
2024
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