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Aims/hypothesis <p>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 &lt;8 years with stage 2 type 1 diabetes.</p> Methods <p>The PETITE-T1D trial is a 2 year single-arm, open-label, multicentre study of 23 children &lt;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.</p> Results <p>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.</p> Conclusions/interpretation <p>Teplizumab was safe and well tolerated in children &lt;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.</p> Trial registration <p>ClinicalTrials.gov NCT05757713.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月6日

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  • Stephen E. Gitelman,
  • Kimber Simmons,
  • Jennifer L. Sherr,
  • Steven B. Leichter,
  • Teresa Quattrin,
  • William E. Russell,
  • Bhuvana Sunil,
  • Steven M. Willi,
  • Laura A. Knecht,
  • Elisabeth Niemoeller,
  • Idlir Licaj,
  • Wolfgang Schmider,
  • Diana Miller,
  • Linda A. DiMeglio

摘要

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.

Graphical Abstract