Teplizumab preserves C-peptide in recent-onset type 1 diabetes: 2-year results from the randomized, placebo-controlled Protégé trial

  1. for the Protégé Trial Investigators*
  1. 1Pacific Northwest Diabetes Research Institute, Seattle, WA
  2. 2Division of Pediatric Endocrinology and Metabolism, Le Bonheur Children’s Hospital and University of Tennessee Health Science Center, Memphis, TN
  3. 3Massachusetts General Hospital, Boston, MA
  4. 4MacroGenics, Rockville, MD
  5. 5Departments of Immunobiology and Internal Medicine, Yale University, New Haven, CT
  6. 6Division of Pediatrics, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Linköping, Sweden
  1. Corresponding author: William Hagopian, E-mail: wah{at}uw.edu

Abstract

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.

Footnotes

  • * A list of all investigators appears online in the Appendix

  • Received February 13, 2013.
  • Accepted June 18, 2013.

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