INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes

Abstract

Background: The INNODIA consortium has established a pan-European infrastructure using validated centres to evaluate prospectively clinical data from individuals with newly diagnosed Type 1 diabetes combined with centralized collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of Phase 2 clinical trials. Methods: In this context we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of Phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed Type 1 diabetes. Although many IMPs have demonstrated potential efficacy in Phase 2 studies, few subsequent Phase 3 studies have confirmed these benefits. Currently Phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion: The Master Protocol provides: 1) standardized assessment of efficacy and safety; 2) comparable collection of mechanistic data; 3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies; 4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers.