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 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 bet...
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| Format: | Article |
| Language: | English |
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BMC
2022-05-01
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| Series: | Trials |
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| Online Access: | https://doi.org/10.1186/s13063-022-06259-z |
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| author | David B. Dunger Sylvaine F. A. Bruggraber Adrian P. Mander M. Loredana Marcovecchio Timothy Tree Piotr Jaroslaw Chmura Mikael Knip Anke M. Schulte Chantal Mathieu on behalf of the INNODIA consortium |
| author_facet | David B. Dunger Sylvaine F. A. Bruggraber Adrian P. Mander M. Loredana Marcovecchio Timothy Tree Piotr Jaroslaw Chmura Mikael Knip Anke M. Schulte Chantal Mathieu on behalf of the INNODIA consortium |
| author_sort | David B. Dunger |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T12:49:20Z |
| format | Article |
| id | doaj.art-579881137eaa49e583e9b682b21fba96 |
| institution | Directory Open Access Journal |
| issn | 1745-6215 |
| language | English |
| last_indexed | 2024-12-12T12:49:20Z |
| publishDate | 2022-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Trials |
| spelling | doaj.art-579881137eaa49e583e9b682b21fba962022-12-22T00:24:01ZengBMCTrials1745-62152022-05-012311910.1186/s13063-022-06259-zINNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetesDavid B. Dunger0Sylvaine F. A. Bruggraber1Adrian P. Mander2M. Loredana Marcovecchio3Timothy Tree4Piotr Jaroslaw Chmura5Mikael Knip6Anke M. Schulte7Chantal Mathieu8on behalf of the INNODIA consortiumDepartment of Paediatrics, University of CambridgeDepartment of Paediatrics, University of CambridgeCentre for Trials Research, Cardiff UniversityDepartment of Paediatrics, University of CambridgeCentre for Trials Research, Cardiff UniversityNovo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of CopenhagenPediatric Research Centre, Children’s Hospital, University of Helsinki and Helsinki University HospitalBayer AGDepartment of Endocrinology, KU LeuvenAbstract 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.https://doi.org/10.1186/s13063-022-06259-zBeta-cell functionC-peptideMaster protocolPhase 2PreventionTrials |
| spellingShingle | David B. Dunger Sylvaine F. A. Bruggraber Adrian P. Mander M. Loredana Marcovecchio Timothy Tree Piotr Jaroslaw Chmura Mikael Knip Anke M. Schulte Chantal Mathieu on behalf of the INNODIA consortium INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes Trials Beta-cell function C-peptide Master protocol Phase 2 Prevention Trials |
| title | INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes |
| title_full | INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes |
| title_fullStr | INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes |
| title_full_unstemmed | INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes |
| title_short | INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes |
| title_sort | innodia master protocol for the evaluation of investigational medicinal products in children adolescents and adults with newly diagnosed type 1 diabetes |
| topic | Beta-cell function C-peptide Master protocol Phase 2 Prevention Trials |
| url | https://doi.org/10.1186/s13063-022-06259-z |
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