Protégé: Anti-CD3 (teplizumab) in recent-onset type 1 diabetes

Note on registry ID: This record was requested under NCT00378508, but that number belongs to a separate, small (n=63) Yale University Phase 2 teplizumab study.¹ The large Protégé trial described here is registered as NCT00385697 — confirmed both by the registry's own brief title ("The Protégé Study") and by the published results paper.²³ This record uses the correct number.

What was tested and why it matters. Type 1 diabetes happens when the immune system destroys the insulin-making beta cells in the pancreas. Protégé asked whether a short course of teplizumab — an antibody that calms the T cells driving that attack — could protect remaining beta cells in people just diagnosed, preserving some of the body's own insulin.³ Holding onto even a little natural insulin production makes blood sugar easier to control and lowers the risk of dangerous lows.³

Who it was for. People aged 8–35 diagnosed with type 1 diabetes within the previous 12 weeks, with a positive islet autoantibody and still-detectable C-peptide (a marker of their own insulin).³

Design. A Phase 2/3, randomized, double-blind, placebo-controlled trial run at 83 centres across North America, Europe, Israel and India.³ 763 people were screened and 516 randomized (2:1:1:1) to one of three teplizumab regimens or placebo, each given over 14 days at baseline and again at 26 weeks, with 2 years of follow-up.³

Key results. The trial missed its main goal. At 1 year, the composite of low insulin use plus good HbA1c was essentially identical to placebo: 19.8% on full-dose teplizumab versus 20.4% on placebo.³ But exploratory analyses told a more hopeful story — teplizumab slowed the loss of C-peptide, and by 2 years this difference reached statistical significance for the full-dose group (a prespecified secondary endpoint).⁴ The benefit was clearest in children aged 8–11, US participants, and those treated within 6 weeks of diagnosis.³⁴ About 5% of teplizumab-treated patients were off insulin at 1 year versus none on placebo.³ Rash was the commonest side effect (53% vs 20%); serious adverse events matched placebo (~10%).³

What it means / what's next. Protégé showed teplizumab works but that the original endpoint was wrong, and that treating young patients early matters most.³ Those lessons directly shaped the later prevention trial (TN-10) that led to teplizumab's 2022 FDA approval (Tzield) for delaying type 1 diabetes onset.⁴

References

1. U.S. National Library of Medicine. Anti-CD3 mAb Treatment of Recent Onset Type 1 Diabetes (Yale University, Phase 2, n=63). ClinicalTrials.gov (NCT00378508). https://clinicaltrials.gov/study/NCT00378508 ↩

2. U.S. National Library of Medicine. The Protégé Study — Clinical Trial of MGA031 in Children and Adults With Recent-Onset Type 1 Diabetes Mellitus. ClinicalTrials.gov (NCT00385697). https://clinicaltrials.gov/study/NCT00385697 ↩

3. Sherry N, Hagopian W, Ludvigsson J, et al. Teplizumab for treatment of type 1 diabetes (Protégé study): 1-year results from a randomised, placebo-controlled trial. Lancet (2011); 378(9790):487–97. https://doi.org/10.1016/S0140-6736%2811%2960931-8 ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰ ↩¹¹

4. Hagopian W, Ferry RJ, Sherry N, et al. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized, placebo-controlled Protégé trial. Diabetes (2013); 62(11):3901–8. https://doi.org/10.2337/db13-0236 ↩ ↩² ↩³