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. 2022 May 18;23(1):414.
doi: 10.1186/s13063-022-06259-z.

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

David B Dunger  1   2 , Sylvaine F A Bruggraber  1 , Adrian P Mander  3   4 , M Loredana Marcovecchio  5 , Timothy Tree  3   4 , Piotr Jaroslaw Chmura  6 , Mikael Knip  7 , Anke M Schulte  8 , Chantal Mathieu  9 ; INNODIA consortium
Collaborators, Affiliations

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

David B Dunger et al. Trials. .

Abstract

Background: The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised 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) standardised 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, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers.

Keywords: Beta-cell function; C-peptide; Master protocol; Phase 2; Prevention; Trials; Type 1 diabetes.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
INNODIA Natural history study backbone
Fig. 2
Fig. 2
Adaption of the Master Protocol for a clinical trial (example MELD-ATG study)
Fig. 3
Fig. 3
The regulatory framework for the INNODIA Master Protocol
See this image and copyright information in PMC

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