Safety and pharmacokinetics of teplizumab in children less than 8 years of age with stage 2 type 1 diabetes
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Diabetologia
Institutions: University of California, San Francisco, University of Colorado Anschutz, University of Colorado Denver, Yale University, Mercer University, University at Buffalo, State University of New York, Vanderbilt University, Vanderbilt University Medical Center, Mary Bridge Children's Health Center, Children's Hospital of Philadelphia, University of Pennsylvania, Sanofi (Germany), Sanofi (France), Indiana University Indianapolis, Indiana University School of Medicine, Indiana University – Purdue University Indianapolis
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,490
OpenAlex ID: W4415955324