Background & Aims: Teplizumab is an anti-CD3 mAb approved for delaying onset of Stage 3 T1D in people ≥8 years old with Stage 2 T1D. In the PROTECT study intent-to-treat (ITT) population, teplizumab demonstrated significantly greater β‑cell function preservation vs placebo (PBO; least-squares mean difference of C-peptide ln(AUC+1) change from baseline to Week 78 between teplizumab and PBO was 0.13 pmol/mL; p<0.001). In the ITT population, insulin dose was lower with teplizumab vs PBO from Week 12. Here we explore reduction in insulin dose and sustained glycemic control in the per-protocol (PP) population.
Methods: The Phase 3 PROTECT study (NCT03875729) of 8-17-year-olds with Stage 3 T1D, diagnosed ≤6 weeks, randomized participants 2:1 to two 12-day courses of teplizumab or PBO. The PP population excluded those who received incorrect treatment, took prohibited medications, became pregnant, or had <80% treatment compliance.
Results: In the PP analysis, teplizumab showed consistent results in reduced insulin dose, and greater % time in range (TIR) vs the PBO group (Table); HbA1c levels were not significantly different between groups.
Conclusions: Participants treated with teplizumab showed greater β-cell function preservation and clinically relevant metabolic outcomes including lower insulin doses and greater TIR vs PBO.
K.C. Herold: Consultant; Sanofi. C. Dayan: Consultant; Provention Bio, Inc., Sanofi. Other Relationship; Dompé. Advisory Panel; Avotres Inc., Amgen Inc. L. Chatenoud: Consultant; Provention Bio, Inc., Sanofi. S.E. Gitelman: Advisory Panel; Abata Therapeutics, Avotres Inc., Genentech, Inc., GentiBio, SAB Biotherapeutics, Inc., Sanofi. Z. Sumnik: None. K.M. Simmons: Advisory Panel; Provention Bio, Inc. Consultant; Provention Bio, Inc. Research Support; Provention Bio, Inc., Novartis AG. Consultant; Medtronic. A. Szypowska: Speaker's Bureau; Abbott. Advisory Panel; Dexcom, Inc., Medtronic. Speaker's Bureau; Sanofi, Novo Nordisk. Advisory Panel; SYNOPIS Pharma, Proglikemia. Research Support; Provention Bio, Inc. L. Knecht: Employee; Sanofi, Provention Bio, Inc. E. Niemoeller: Employee; Sanofi-Aventis Deutschland GmbH. Stock/Shareholder; Sanofi. W. Tian: Employee; Sanofi. E.L. Ramos: None.
Provention Bio, a Sanofi company
