P4.A014: Teplizumab in children with newly diagnosed type 1 diabetes (T1D): outcomes from the Phase 3 PROTECT study

Background: Teplizumab is a humanized monoclonal antibody that binds the T-cell CD3 receptor and inhibits the autoimmune process underlying T1D. The PROTECT study (NCT03875729) was designed to assess β-cell preservation and the safety of teplizumab in newly diagnosed T1D.

Methods: Patients (pts) aged 8–17 yrs within 6 wks of T1D diagnosis were randomized 2:1 to receive 12 days of IV teplizumab or placebo at baseline and 6 months. Stimulated C-peptide responses were measured. Primary endpoint was the difference between treatment groups in mean change in C-peptide (area under the curve ln[AUC]+1) from baseline to Week 78 in the Intent-to-Treat population. Differences in mean continuous glucose monitoring-measured time in range, insulin use, HbA1c and clinically important hypoglycemia were evaluated at Week 78. Adverse events (AEs) were assessed.

Results: The primary endpoint was met. At Week 78, pts treated with teplizumab (n=217) had significantly greater stimulated C-peptide vs placebo (n=111; difference in least squares means [LSmean] 0.13 pmol/mL [95% CI 0.085, 0.165; P< 0.001]), with 95% maintaining clinically meaningful peak C-peptide levels ≥0.2 pmol/mL vs 79% on placebo (P < 0.001). The difference in LSmean for insulin use for teplizumab vs placebo at Week 78 was –0.13 U/kg/day (95% CI −0.280, 0.018; P=0.085; ANCOVA) and –0.14 U/kg/day (95% CI −0.230, −0.051; P=0.002; MMRM). More patients met remission criteria (HbA1c ≤6.5% and insulin dose ≤0.25 units/kg/day) in the teplizumab group throughout the study. The most common AEs (≥30%) were hypoglycemia, headache, nausea, rash, lymphopenia and vomiting. Serious AEs were reported in 5.5% of pts in teplizumab and 5.4% on placebo, the most common being cytokine release syndrome (teplizumab 1.4%) and infections (placebo 2.7%).

Conclusion: The PROTECT study showed that teplizumab reduced the decline in β-cell function and resulted in measurable clinical benefits that were sustained through 78 wks.

This study was funded by Provention Bio, Inc., a Sanofi Company.