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Phase 3CompletedNCT03875729

PROTECT: Teplizumab in children and adolescents with recent-onset type 1 diabetes

A Phase 3 trial testing whether two short courses of the immune therapy teplizumab can preserve the body's own insulin production in 8-17-year-olds newly diagnosed with type 1 diabetes. Teplizumab significantly preserved C-peptide (a measure of remaining insulin-making capacity) versus placebo at 18 months, though day-to-day diabetes measures (insulin dose, HbA1c, time in range) did not differ.

Primary endpoints

  • Change from baseline in stimulated C-peptide (β-cell function), measured by mixed-meal tolerance test, at week 78

Results so far

Met its primary endpoint: at 18 months, teplizumab-treated patients had significantly higher stimulated C-peptide than placebo (least-squares mean difference 0.13 pmol/mL; 95% CI 0.09-0.17; P<0.001), and 94.9% of treated patients vs 79.2% on placebo retained a clinically meaningful peak C-peptide of at least 0.2 pmol/mL. However, the key secondary endpoints (insulin dose, HbA1c, time in range, hypoglycemia) did not differ significantly between groups. Common side effects included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome.

The full picture

What PROTECT tested and why it matters

In type 1 diabetes, the immune system attacks the insulin-making beta cells in the pancreas. At diagnosis, most people still have some working beta cells — a "honeymoon" window that fades over months to years. PROTECT asked a focused question: can a short course of the immune therapy teplizumab, given right after diagnosis, slow that loss and protect the body's own insulin production?1

Teplizumab is an anti-CD3 monoclonal antibody that dampens the T cells driving the attack.1 It is FDA-approved (as Tzield) to delay the onset of clinical (stage 3) diabetes in people aged 1 and older who have earlier-stage (stage 2) disease, and the FDA granted accelerated approval in 2026 for the newly diagnosed 8-17 age group PROTECT studied.2 PROTECT asked the further question: does it help people who have already been diagnosed?1

Who it was for

PROTECT enrolled 328 children and adolescents aged 8-17 who had been diagnosed with type 1 diabetes within the previous 6 weeks, had positive diabetes autoantibodies, and still had measurable insulin production.13 It ran across roughly 47 sites in the US, Canada, the UK, and several European countries.3

How it was designed

This was a Phase 3, randomized, double-blind, placebo-controlled trial.1 Participants were assigned 2:1 to teplizumab (217) or placebo (111), each given as two 12-day intravenous courses six months apart.13 The main outcome was the change in stimulated C-peptide — a blood marker of how much insulin the pancreas can still make — measured at week 78 (about 18 months).13

Key results

PROTECT met its primary goal. At week 78, teplizumab-treated patients had significantly higher stimulated C-peptide than the placebo group (least-squares mean difference 0.13 pmol/mL; 95% CI 0.09-0.17; P<0.001).1 Nearly all treated patients (94.9%) kept a clinically meaningful C-peptide level of at least 0.2 pmol/mL, versus 79.2% on placebo.1

Importantly, the day-to-day diabetes measures that matter most to patients — insulin dose, HbA1c, time in target glucose range, and hypoglycemia — did not differ significantly between the groups.1 Common side effects were headache, gastrointestinal symptoms, rash, lymphopenia (low white-cell counts), and mild cytokine release syndrome, mostly around the infusions.1

What it means and what's next

PROTECT shows teplizumab can preserve beta-cell function after diagnosis — biological proof that the disease can be slowed even after symptoms begin.1 But because the clinical outcomes did not improve in 18 months, it strengthens the case for using teplizumab earlier (delaying onset) and for combination strategies, while leaving open how much preserving C-peptide changes long-term outcomes.1

References

  1. Ramos EL, Dayan CM, Chatenoud L, et al. Teplizumab and β-Cell Function in Newly Diagnosed Type 1 Diabetes (PROTECT). N Engl J Med (2023). According to PubMed (PMID 37861217); DOI. ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10 ↩11 ↩12 ↩13

  2. U.S. Food and Drug Administration. TZIELD (teplizumab-mzwv) Prescribing Information (2026 label; stage-2 delay indication in adults and pediatric patients 1 year and older; stage-3 new-onset indication in ages 8-17). https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/761183s013lbl.pdf ↩

  3. Provention Bio / Sanofi. Recent-Onset Type 1 Diabetes Trial Evaluating Efficacy and Safety of Teplizumab (PROTECT), NCT03875729. ClinicalTrials.gov (registry record). https://clinicaltrials.gov/study/NCT03875729 ↩ ↩2 ↩3 ↩4