Safety and pharmacokinetics of teplizumab in children less than 8 years of age with stage 2 type 1 diabetes.

AIMS/HYPOTHESIS: Teplizumab is approved in the USA and seven other countries to delay stage 3 type 1 diabetes onset in individuals ≥8 years of age with stage 2 type 1 diabetes. As part of a US Food and Drug Administration post-marketing requirement, this study evaluated the safety, tolerability and pharmacokinetics of teplizumab in children aged <8 years with stage 2 type 1 diabetes. METHODS: The PETITE-T1D trial is a 2 year single-arm, open-label, multicentre study of 23 children <8 years of age with stage 2 type 1 diabetes. Participants received a 14 day teplizumab course. A prespecified interim analysis was performed after 15 participants completed 1 year of follow-up and included all 23 participants. Primary endpoints included treatment-emergent adverse events (TEAEs), TEAEs causing treatment discontinuation, and serious adverse events (SAEs). Other endpoints assessed immunogenicity, pharmacokinetics, pharmacodynamics and time from study treatment to stage 3 type 1 diabetes. RESULTS: Mean participant age was 4.8 years (range 1.7-6.8). Median follow-up duration was 51.9 weeks (range 3.9-77.1). All participants experienced one or more TEAE, with most being mild to moderate. No grade 4 or 5 TEAEs were reported. Three participants (13%) had TEAEs leading to teplizumab discontinuation: anaemia, elevated liver enzymes and maculo-papular rash. Two participants (9%) each had two SAEs. Serum teplizumab concentrations peaked at day 14. Two participants progressed to stage 3 type 1 diabetes. The estimated probability of lack of progression to stage 3 was 89.6% (95% CI 64.3%, 97.3%) at the time of interim analysis. CONCLUSIONS/INTERPRETATION: Teplizumab was safe and well tolerated in children <8 years of age with stage 2 type 1 diabetes. Adverse events were consistent with those seen in previous studies, with no new safety risks identified. Two participants progressed to stage 3 type 1 diabetes during the observation period; surveillance is ongoing. TRIAL REGISTRATION: ClinicalTrials.gov NCT05757713.