Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial
Marcovecchio ML., Wicker LS., Dunger DB., Dutton SJ., Kopijasz S., Scudder C., Todd JA., Johnson PRV.
<ns4:p>Type 1 diabetes is a common autoimmune disease due to destruction of pancreatic β cells, resulting in lifelong need for insulin. Evidence suggest that maintaining residual β-cell function can improve glucose control and reduce risk of hypoglycaemia and vascular complications.</ns4:p><ns4:p> Non-clinical, preclinical and some preliminary clinical data suggest that low-dose interleukin-2 (IL-2) therapy could block pancreatic β cells destruction by increasing the number of functional regulatory T cells (Tregs) that inhibit islet-specific autoreactive effector T cells (Teffs). However, there is lack of data on the effect of low-dose IL-2 in newly diagnosed children and adolescents with T1D as well as lack of specific data on its potential effect on β-cell function.</ns4:p><ns4:p> The ‘<ns4:bold>I</ns4:bold>nterleukin-2 <ns4:bold>T</ns4:bold>herapy of <ns4:bold>A</ns4:bold>utoimmunity in <ns4:bold>D</ns4:bold>iabetes (ITAD)’ is a phase 2, multicentre, double-blind, randomised, placebo-controlled trial in children and adolescents (6-18 years; having detectable C-peptide) initiated within 6 weeks of T1D diagnosis. A total of 45 participants will be randomised in a 2:1 ratio to receive either ultra-low dose IL-2 (aldesleukin), at a dose of 0.2 x 10<ns4:sup>6</ns4:sup> IU/m<ns4:sup>2</ns4:sup> twice-weekly, given subcutaneously, or placebo, for 6 months.</ns4:p><ns4:p> The primary objective is to assess the effects of ultra-low dose aldesleukin administration on endogenous β-cell function as measured by frequent home dried blood spot (DBS) fasting and post-prandial C-peptide in children and adolescents with newly diagnosed T1D. The secondary objectives are: 1) to assess the efficacy of regular dosing of aldesleukin in increasing Treg levels; 2) to confirm the clinical safety and tolerability of ultra-low dose aldesleukin; 3) to assess changes in the immune system indicating benefit or potential risk for future gains/loss in β-cell function and immune function; 4) to assess treatment effect on glycaemic control.</ns4:p><ns4:p> Trial registration: EudraCT <ns4:ext-link xmlns:ns3="http://www.w3.org/1999/xlink" ext-link-type="uri" ns3:href="https://www.clinicaltrialsregister.eu/ctr-search/trial/2017-002126-20/GB#N">2017-002126-20</ns4:ext-link> (06/02/2019)</ns4:p>