Preserving beta cell function in children and adolescents with newly diagnosed stage 3 type 1 diabetes: per-protocol population analysis from the PROTECT randomised trial

Abstract Aims/hypothesis In the PROTECT randomised trial, teplizumab demonstrated significantly greater beta cell function preservation vs placebo in the intent-to-treat (ITT) population. Analyses of the pre-specified per-protocol (PP) population and PP subgroups are presented to further evaluate the efficacy of teplizumab. Methods Participants aged 8–17 years with stage 3 type 1 diabetes with a peak stimulated C-peptide level ≥0.2 nmol/l (ITT population: N =328) were randomised 2:1 to receive two 12-day courses of teplizumab or placebo intravenously. Participants with <80% treatment adherence, who took prohibited medication, received incorrect study treatment or were pregnant were excluded from the PP population. Subgroup analyses were based on the presence of HLA-DR3 or HLA-DR4 and the type of baseline type 1 diabetes autoantibodies. Results The PP population comprised 275 participants (teplizumab, n =180; placebo, n =95). At week 78, the primary endpoint of the least squares (LS) mean difference in change of stimulated C-peptide concentration from baseline between teplizumab and placebo was 0.14 nmol/l (95% CI 0.10, 0.18; p <0.001). At week 78, teplizumab treatment significantly reduced the exogenous insulin dose (LS mean difference –0.17 U kg −1 day −1 ; 95% CI –0.26, –0.08; p <0.001) and increased the time in range (TIR) (LS mean difference 6.17%; 95% CI 0.13, 12.2; p <0.05) vs placebo. In subgroup analyses, treatment with teplizumab resulted in higher C-peptide levels compared with placebo, regardless of HLA-DR3/HLA-DR4 presence or baseline type 1 diabetes autoantibodies. Conclusions/interpretation Teplizumab treatment per protocol led to greater beta cell function preservation, greater TIR and lower exogenous insulin use compared with placebo. Beta cell function preservation was maintained irrespective of HLA subtype or the presence of type 1 diabetes autoantibodies. Trial registration ClinicalTrials.gov NCT03875729 Funding The study was funded by Provention Bio, a Sanofi company