Rigby, Mark RDiMeglio, Linda ARendell, Marc SFelner, Eric IDostou, Jean MGitelman, Stephen EPatel, Chetanbabu MGriffin, Kurt JTsalikian, EvaGottlieb, Peter AGreenbaum, Carla JSherry, Nicole AMoore, Wayne VMonzavi, RoshanakWilli, Steven MRaskin, PhilipMoran, AntoinetteRussell, William EPinckney, AshleyKeyes-Elstein, LynetteHowell, MichaelAggarwal, SudeeptaLim, NohaPhippard, DeborahNepom, Gerald TMcNamara, JamesEhlers, Mario R2016-03-032016-03-032013-12Rigby, M. R., DiMeglio, L. A., Rendell, M. S., Felner, E. I., Dostou, J. M., Gitelman, S. E., … the T1DAL Study Team. (2013). Targeting effector memory T cells with alefacept in new onset type 1 diabetes: 12 month results from the T1DAL study. The Lancet. Diabetes & Endocrinology, 1(4), 284–294. http://doi.org/10.1016/S2213-8587(13)70111-62213-8587https://hdl.handle.net/1805/8663Background Type 1 diabetes (T1D) results from autoimmune targeting of the pancreatic beta cells, likely mediated by effector memory T cells (Tems). CD2, a T cell surface protein highly expressed on Tems, is targeted by the fusion protein alefacept, depleting Tems and central memory T cells (Tcms). We hypothesized that alefacept would arrest autoimmunity and preserve residual beta cells in newly diagnosed T1D. Methods The T1DAL study is a phase II, double-blind, placebo-controlled trial that randomised T1D patients 12-35 years old within 100 days of diagnosis, 33 to alefacept (two 12-week courses of 15 mg IM per week, separated by a 12-week pause) and 16 to placebo, at 14 US sites. The primary endpoint was the change from baseline in mean 2-hour C-peptide area under the curve (AUC) at 12 months. This trial is registered with ClinicalTrials.gov, number NCT00965458. Findings The mean 2-hour C-peptide AUC at 12 months increased by 0.015 nmol/L (95% CI -0.080 to 0.110 nmol/L) in the alefacept group and decreased by 0.115 nmol/L (95% CI -0.278 to 0.047) in the placebo group, which was not significant (p=0.065). However, key secondary endpoints were met: the mean 4-hour C-peptide AUC was significantly higher (p=0.019), and daily insulin use and the rate of hypoglycemic events were significantly lower (p=0.02 and p<0.001, respectively) at 12 months in the alefacept vs. placebo groups. Safety and tolerability were comparable between groups. There was targeted depletion of Tems and Tcms, with sparing of naïve and regulatory T cells (Tregs). Interpretation At 12 months, alefacept preserved the 4-hour C-peptide AUC, lowered insulin use, and reduced hypoglycemic events, suggesting a signal of efficacy. Depletion of memory T cells with sparing of Tregs may be a useful strategy to preserve beta cell function in new-onset T1D.en-USPublisher PolicyDiabetes Mellitus, Type 1blooddrug therapyDrug Delivery SystemsmethodsImmunologic Memorydrug effectsRecombinant Fusion Proteinsadministration & dosageT-LymphocytesArticle