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
10 affiliations
- 1Department of Immunobiology, Yale School of Medicine, New Haven, Connecticut USA
- 2Department of Endocrinology, Cardiff University School of Medicine, Cardiff, UK
- 3Université Paris Cité, CNRS, Inserm, Institut Necker Enfants Malades-INEM, Paris, France
- 4Department of Pediatrics, University of California San Francisco, San Francisco, CA USA
- 5Department of Pediatrics, Motol University Hospital and 2nd Faculty of Medicine, Prague, Czechia
- 6Barbara Davis Center for Diabetes/University of Colorado School of Medicine, Aurora, CO USA
- 7Department of Pediatric Diabetology and Paediatrics, Medical University of Warsaw, Warsaw, Poland
- 8Sanofi, Morristown, NJ USA
- 9Sanofi, Industrial Park Höchst, G879, Frankfurt am Main, Germany
- 10Provention Bio, Morristown, NJ USA
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
Graphical Abstract:
Supplementary Information: The online version of this article (https://doi.org/10.1007/s00125-026-06849-5) contains peer-reviewed but unedited supplementary material.
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BibTeX
@article{herold2026preserving,
title = {{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}},
author = {Kevan C. Herold and Colin M. Dayan and Lucienne Chatenoud and Stephen E. Gitelman and Zdenek Sumnik and Kimber Simmons and Agnieszka Szypowska and Laura A. Knecht and Elisabeth Niemoeller and Mark R. Rigby and Wei Tian and Robert Hill and Eleanor L. Ramos},
journal = {Diabetologia},
year = {2026},
month = sep,
doi = {10.1007/s00125-026-06849-5},
url = {https://doi.org/10.1007/s00125-026-06849-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - 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
AU - Kevan C. Herold
AU - Colin M. Dayan
AU - Lucienne Chatenoud
AU - Stephen E. Gitelman
AU - Zdenek Sumnik
AU - Kimber Simmons
AU - Agnieszka Szypowska
AU - Laura A. Knecht
AU - Elisabeth Niemoeller
AU - Mark R. Rigby
AU - Wei Tian
AU - Robert Hill
AU - Eleanor L. Ramos
PY - 2026
DA - 2026/09/10
JO - Diabetologia
DO - 10.1007/s00125-026-06849-5
UR - https://doi.org/10.1007/s00125-026-06849-5
AB - 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 Graphical Abstract: Supplementary Information: The online version of this article (https://doi.org/10.1007/s00125-026-06849-5) contains peer-reviewed but unedited supplementary material.
SN - 0012-186X
SN - 1432-0428
ER -