Protégé was a Phase 3, randomized, double-blind, parallel, placebo-controlled 2-year study of three intravenous teplizumab dosing regimens, administered daily for 14 days at baseline and again after 26 weeks, in new-onset type 1 diabetes. We sought to determine efficacy and safety of teplizumab immunotherapy at 2 years, and to identify characteristics associated with therapeutic response. Of 516 randomized patients, 513 were treated, and 462 completed 2 years follow-up. Teplizumab (14-day full-dose) reduced the loss of C-peptide mean AUC (a pre-specified secondary endpoint) at 2 years versus placebo. In analyses of pre-specified and post-hoc subsets at entry, US residents, patients with C-peptide mean AUC >0.2nmol/L, those randomized ≤6 weeks after diagnosis, HbA1c <7.5% (58 mmol/mol), insulin use <0.4U/kg/day, and ages 8-17 each had greater teplizumab-associated C-peptide preservation than their counterparts. Exogenous insulin needs tended to be reduced versus placebo. Anti-drug antibodies developed in some patients without apparent change in drug efficacy. No new safety or tolerability issues were observed during Year 2. In summary, anti-CD3 therapy reduced C-peptide loss 2 years after diagnosis using a tolerable dose.
* A list of all investigators appears online in the Appendix
- Received February 13, 2013.
- Accepted June 18, 2013.
- © 2013 by the American Diabetes Association.
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