Periodic Reporting for period 8 - INNODIA (Translational approaches to disease modifying therapy of type 1 diabetes: an innovative approach towards understanding and arresting type 1 diabetes – Sofia ref.: 115797)
Berichtszeitraum: 2022-11-01 bis 2023-10-31
The overall objective of INNODIA is to advance in how we predict, stage, evaluate and prevent type 1 diabetes (T1D). Therefore, this project aimed to (1) establish an EU infrastructure of clinical sites for recruitment and bio-sampling; (2) establish a network of basic and clinical researchers collaborating to address knowledge gaps in T1D pathogenesis; (3) develop and incorporate new methods and technologies; (4) establish a unique integrated database fueling the discovery of new disease targets/biomarkers and (5) conceive innovative clinical trial design. We have achieved all milestones and deliverables through a unique partnership between academic and industry partners and by introducing the most crucial partner: the person living with diabetes, i.e. Patient Advisory Committee (PAC). We have conducted a natural history study, collecting a vast array of bio-samples and analyzing these samples using state-of-the-art and innovative multi-omics technologies, centralizing all data and results in one central INNODIA database. We executed a clinical trial, studying anti-thymocyte globulin in different doses (MELD-ATG) in people with newly diagnosed T1D and launched the concept of master protocols for conduct of disease modifying therapies in T1D, with the scientific guidance of the European Medicines Agency (EMA). Despite running during the COVID pandemic, the INNODIA project was successful in putting T1D research in Europe on the map again and has a legacy in the creation of a non-profit organization INNODIA iVZW.
The INNODIA project was launched in November 2015. Ending in October 2023, INNODIA can be considered a successful project, with all milestones and deliverables reached, despite that this project ran during the COVID pandemic. This project leveraged an EU-wide, scientific network for T1D research and generated ±230 peer-reviewed publications. Our most important realizations are:
- The set-up and conduct of a natural history study, including the follow-up of 743 people with newly diagnosed clinical T1D, with the collection of bio-samples and clinical data. Of the +5300 unaffected first-degree relatives, 361 accepted to be followed up intensively.
- Standardization of sample collection protocols and of sample analyses. In the beginning, we spent 1 year in standardization of sample collection protocols and analyses alignment in labs. This allowed us to collect samples of high quality.
- Highlighting the potential and the limits of multi-omics analysis. In the natural history study, thousands of data were generated from different omics platforms. First multi-omics analysis has been presented at scientific conferences.
- Integration of basic, translational and clinical scientific communities in research. Bringing together different profiles of researchers is essential for stimulation of all types of research. Insights on the lethal dialogue between the insulin-producing beta-cell and the immune system gained in INNODIA have unraveled the T1D pathogenesis and have pointed the direction for further research and potential novel interventions.
- The creation of Master protocols for follow-up and conduct of clinical trials of disease modifying therapy in all stages of T1D. All protocols got scientific advice from EMA and are publicly available, some of which published in peer-reviewed journals.
- Execution of a clinical trial by an academic sponsor and with industry IMP: the MELD-ATG trial. The main objective of the MELD-ATG trial was to test the efficacy and safety of the Minimal Effective Low Dose of ATG in people with newly diagnosed stage 3 T1D. This trial included 114 people, and was fully recruited by January 2024. Safety data are reassuring and outcome results are to be expected Q2 of 2025.
- Creation of innovative clinical trial designs and a ‘clinical trial community’. From the start, we have put standardization of processes and accreditation of clinical centers as one of the highest priorities. To prioritize trials in the capacity of the network, we established an INNODIA Clinical Trials Prioritization Committee. In the MELD-ATG trial an intense collaboration between clinicians, biomarker specialists, PAC, ethics advisory board and statisticians has created a unique community allowing the running of a complex clinical trial.
- The most important realization of INNODIA, was the creation of the PAC: the ‘patient’ advisory committee. This concept was piloted in INNODIA as the first IMI project to introduce a PAC. This PAC was instrumental in establishing protocols for the natural history studies, helping with the design of educational materials, guiding our work on the Master protocols for disease modifying therapies in T1D, and were crucial motivators for basic researchers.
- INNODIA branding: Communication to peers and to the general public was central in the INNODIA project, with ample tools created (incl. Newsletters, website adjustments, media & social media, video materials). INNODIA has become a brand in the T1D filed, partly thanks to the many presentations at all international scientific conferences (ATTD, ADA, EASD and IDS).
- INNODIA legacy: We have created a community in T1D in Europe. We have put Europe on the map in T1D research and have become a ‘go-to’ community for clinical trials of disease modifying therapies in T1D. Through the support of research by many young investigators in INNODIA, we have supported many PhDs and postdoctoral researchers. The ultimate legacy of INNODIA has been the creation of the non-profit organization INNODIA iVZW.
- The set-up and conduct of a natural history study, including the follow-up of 743 people with newly diagnosed clinical T1D, with the collection of bio-samples and clinical data. Of the +5300 unaffected first-degree relatives, 361 accepted to be followed up intensively.
- Standardization of sample collection protocols and of sample analyses. In the beginning, we spent 1 year in standardization of sample collection protocols and analyses alignment in labs. This allowed us to collect samples of high quality.
- Highlighting the potential and the limits of multi-omics analysis. In the natural history study, thousands of data were generated from different omics platforms. First multi-omics analysis has been presented at scientific conferences.
- Integration of basic, translational and clinical scientific communities in research. Bringing together different profiles of researchers is essential for stimulation of all types of research. Insights on the lethal dialogue between the insulin-producing beta-cell and the immune system gained in INNODIA have unraveled the T1D pathogenesis and have pointed the direction for further research and potential novel interventions.
- The creation of Master protocols for follow-up and conduct of clinical trials of disease modifying therapy in all stages of T1D. All protocols got scientific advice from EMA and are publicly available, some of which published in peer-reviewed journals.
- Execution of a clinical trial by an academic sponsor and with industry IMP: the MELD-ATG trial. The main objective of the MELD-ATG trial was to test the efficacy and safety of the Minimal Effective Low Dose of ATG in people with newly diagnosed stage 3 T1D. This trial included 114 people, and was fully recruited by January 2024. Safety data are reassuring and outcome results are to be expected Q2 of 2025.
- Creation of innovative clinical trial designs and a ‘clinical trial community’. From the start, we have put standardization of processes and accreditation of clinical centers as one of the highest priorities. To prioritize trials in the capacity of the network, we established an INNODIA Clinical Trials Prioritization Committee. In the MELD-ATG trial an intense collaboration between clinicians, biomarker specialists, PAC, ethics advisory board and statisticians has created a unique community allowing the running of a complex clinical trial.
- The most important realization of INNODIA, was the creation of the PAC: the ‘patient’ advisory committee. This concept was piloted in INNODIA as the first IMI project to introduce a PAC. This PAC was instrumental in establishing protocols for the natural history studies, helping with the design of educational materials, guiding our work on the Master protocols for disease modifying therapies in T1D, and were crucial motivators for basic researchers.
- INNODIA branding: Communication to peers and to the general public was central in the INNODIA project, with ample tools created (incl. Newsletters, website adjustments, media & social media, video materials). INNODIA has become a brand in the T1D filed, partly thanks to the many presentations at all international scientific conferences (ATTD, ADA, EASD and IDS).
- INNODIA legacy: We have created a community in T1D in Europe. We have put Europe on the map in T1D research and have become a ‘go-to’ community for clinical trials of disease modifying therapies in T1D. Through the support of research by many young investigators in INNODIA, we have supported many PhDs and postdoctoral researchers. The ultimate legacy of INNODIA has been the creation of the non-profit organization INNODIA iVZW.
The intense collaborations in INNODIA lead to realizations beyond the initial objective and aims. Building on the strong foundations of INNODIA, the consortium started a ‘sister’ project, INNODIA HARVEST, aiming to harvest the fruits – the achievements – of INNODIA (May 2020 – April 2024). Furthermore, the tight collaboration of INNODIA scientists across Europe has been a nucleus to extend the focus towards prediction and prevention in type-1 diabetes within a new IHI consortium (EDENT1FI). Finally, INNODIA had a strong impact on newly diagnosed T1D patients and their families by offering access to different clinical interventions and disease modifying therapies in various European countries, providing vision and hope.
INNODIA and INNODIA HARVEST have leveraged an EU-wide, best-in-class collaborative clinical trials network for T1D. To continue this work, a non-profit organization INNODIA iVZW has been created on July 28, 2022 (https://www.innodia.org/). INNODIA iVZW offers scientific expert advice, access to accredited clinical trial sites, clinical trial support, education and training activities, and access to data and samples. Additionally, it provides insights from the professional experiences of people and families living with T1D through the creation of an INPACT group. This way, the organization engages a diverse array of stakeholders, including medicine developers, clinical trial sites, research and innovation labs, individuals living with T1D, and entities interested in T1D research and solutions. The network is constantly expanding and currently comprises 98 members, including 85 clinical trial sites, with the overall goal to foster T1D research and development in Europe.
INNODIA and INNODIA HARVEST have leveraged an EU-wide, best-in-class collaborative clinical trials network for T1D. To continue this work, a non-profit organization INNODIA iVZW has been created on July 28, 2022 (https://www.innodia.org/). INNODIA iVZW offers scientific expert advice, access to accredited clinical trial sites, clinical trial support, education and training activities, and access to data and samples. Additionally, it provides insights from the professional experiences of people and families living with T1D through the creation of an INPACT group. This way, the organization engages a diverse array of stakeholders, including medicine developers, clinical trial sites, research and innovation labs, individuals living with T1D, and entities interested in T1D research and solutions. The network is constantly expanding and currently comprises 98 members, including 85 clinical trial sites, with the overall goal to foster T1D research and development in Europe.