Interleukin-2 Therapy of Autoimmunity in Diabetes (ITAD): a phase 2, multicentre, double-blind, randomized, placebo-controlled trial

Wellcome Open Research

article

M. Loredana Marcovecchio¹  Linda S. Wicker²  David B. Dunger¹  Susan J. Dutton⁴  Sylwia Kopijasz²  Claire Scudder²  John A. Todd²  Paul R. V. Johnson⁵ 

[1] Department of Paediatrics, University of Cambridge;JDRF/Wellcome Diabetes and Inflammation Laboratory, Nuffield Department of Medicine, Wellcome Centre for Human Genetics, NIHR Oxford Biomedical Research Centre, University of Oxford;Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge;Oxford Clinical Trials Research Unit, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford;Islet Transplant Research Group, Nuffield Department of Surgical Sciences, Centre for Diabetes, Endocrinology and Metabolism ,(OCDEM), University of Oxford

关键词: type 1 diabetes;    children;    adolescents;    immunotherapy;    Interleukin-2;    aldesleukin;    Beta cells;    C-peptide;    Treg;   

DOI  :  10.12688/wellcomeopenres.15697.1

学科分类：内科医学

来源: Wellcome

【 摘 要 】

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. 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. The ‘Interleukin-2Therapy ofAutoimmunity inDiabetes (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 106 IU/m2 twice-weekly, given subcutaneously, or placebo, for 6 months. 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.

【 授权许可】

CC BY