Periodic Reporting for period 3 - INNODIA HARVEST (Translational approaches to disease modifying therapy of type 1 diabetes - HARVESTing the fruits of INNODIA)
Período documentado: 2023-05-01 hasta 2024-04-30
INNODIA HARVEST aimed to harvest the fruits – the achievements – of its sister project INNODIA. Building on the strong foundations of INNODIA, the overall objective of INNODIA HARVEST was to consolidate a sustainable type 1 diabetes (T1D) network in Europe that matched discovery science to clinical advances for patient benefit at an unprecedented scale. Thereby, this project intended to accelerate collaboration and the discovery of disease-modifying therapies, new biomarkers and new insights in T1D disease processes. As in INNODIA, the voice of people living with T1D and their families held a central place in INNODIA HARVEST to drive implementation of new, patient-proximal outcomes, shape our clinical trials, and bring about a meaningful change in disease perspective.
The first goal of INNODIA HARVEST was to consolidate the INNODIA clinical network as the reference point for conducting studies to arrest T1D. We were able to transform the INNODIA clinical network into an accredited clinical trial network of 15 centers in Europe and UK. Three clinical studies were run during the project period: Ver-A-T1D, IMPACT and CFZ533 (Iscalimab). Ver-A-T1D is an academia-driven study investigating the effect of verapamil sustained release on preservation of beta-cell function in adults with newly-diagnosed (ND) T1D. 136 participants were enrolled in the study. Recruitment was completed in April 2024 and results are expected in Q2 2025. The Iscalimab study, sponsored by Novartis, aimed to evaluate the safety, tolerability and efficacy of CFZ533 (Iscalimab) in pediatric and young adults with ND T1D. 7 patients were recruited and randomized by 4 INNODIA HARVEST sites. Due to strategic reasons, the trial was terminated early by Novartis in December 2022. Finally the IMPACT study, sponsored by Imcyse, investigated the efficacy of a novel immunotherapy to stop the loss of beta cells in ND T1D. In collaboration with 12 INNODIA HARVEST sites, enrolment of the study was completed in February 2023. A total of 110 participants were randomized. The analysis of the 1-year follow-up dataset has been concluded and results have been reported in Q4 2024. On top of this, a master protocol to explore the use of single or combinations of Investigational Medicinal Products in people with ND T1D was designed and published, promoting a speedy evaluation and comparison of different clinical trials (with positive advice from EMA).
Our second goal was to introduce novel biomarkers, both clinical (continuous glucose monitoring (CGM)) and experimental (gut microbiome analysis), to ease disease heterogeneity and identify new endpoints to accelerate identification of effective therapeutics. We characterized the intestinal microbiome composition in stool samples of 98 individuals with ND T1D and 194 autoantibody-positive unaffected family members (people with increased T1D risk). Wearable devices to facilitate CGM have been implemented in INNODIA HARVEST clinical trials including Ver-A-T1D, IMPACT and CFZ533/Iscalimab, as well as in the INNODIA natural history study. We designed ‘standard operating procedures’ for clinicians indicating how to analyze CGM data. Finally, biomarker analysis was performed on blood samples from the IMPACT study. All data acquisition has been completed and results are being correlated with clinical outcome.
Thirdly, we focused on fundamental/basic research to identify new mechanisms and technologies in T1D disease processes. Multiple key mechanisms and methods were identified which improve understanding of mechanisms underlying the disease development. Major portions of the work have been published in high ranking journals with many of them based on two or more collaborators on the project.
Next to the overall project management, we have put specific effort in communication and project sustainability. We worked intensively on branding of the INNODIA/INNODIA HARVEST network (https://www.innodia.eu/) and created the non-profit organization INNODIA iVZW on July 28, 2022 (https://www.innodia.org/).
Our second goal was to introduce novel biomarkers, both clinical (continuous glucose monitoring (CGM)) and experimental (gut microbiome analysis), to ease disease heterogeneity and identify new endpoints to accelerate identification of effective therapeutics. We characterized the intestinal microbiome composition in stool samples of 98 individuals with ND T1D and 194 autoantibody-positive unaffected family members (people with increased T1D risk). Wearable devices to facilitate CGM have been implemented in INNODIA HARVEST clinical trials including Ver-A-T1D, IMPACT and CFZ533/Iscalimab, as well as in the INNODIA natural history study. We designed ‘standard operating procedures’ for clinicians indicating how to analyze CGM data. Finally, biomarker analysis was performed on blood samples from the IMPACT study. All data acquisition has been completed and results are being correlated with clinical outcome.
Thirdly, we focused on fundamental/basic research to identify new mechanisms and technologies in T1D disease processes. Multiple key mechanisms and methods were identified which improve understanding of mechanisms underlying the disease development. Major portions of the work have been published in high ranking journals with many of them based on two or more collaborators on the project.
Next to the overall project management, we have put specific effort in communication and project sustainability. We worked intensively on branding of the INNODIA/INNODIA HARVEST network (https://www.innodia.eu/) and created the non-profit organization INNODIA iVZW on July 28, 2022 (https://www.innodia.org/).
INNODIA and INNODIA HARVEST have leveraged an EU-wide, best-in-class collaborative clinical trials network for T1D. This network accelerates the execution of multiple clinical trials at once, and ensures effective development and accessibility of future drugs for people living with T1D. By strengthening and extending the INNODIA HARVEST trial network by satellite centres in many European countries, people living with T1D and their families have access to experts, centres and innovative trials in their home country. The INNODIA HARVEST Patient Advisory Committee (PAC) represents a link to the project’s stakeholders and was instrumental in building trust for people living with T1D.
Besides the impact on people living with T1D, the INNODIA HARVEST clinical trial network supports pharmaceutical companies is developing new immunomodulatory therapies. To successfully develop those new drugs and therapy options, pharmaceutical companies rely on clinical expertise and effective infrastructures in Europe to successfully execute development plans, which we provided during INNODIA HARVEST. In addition, INNODIA HARVEST created a master protocol describing how new studies should be developed, allowing interim analysis and different interventions to be combined in a single trial. The aim is to gain more knowledge as quickly as possible about the effect of drugs and their impact on the progression of T1D in children, adolescents and adults. The established interim analyses helps to decide whether individual interventions or combinations of interventions are promising and whether it makes sense to pursue the approach further. This master protocol can be consulted for future trial designs by pharmaceutical companies or other stakeholders. 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. By doing so, 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. With these goals in mind, The INNODIA iVZW is established as a platform to access smart clinical trial expertise and data on an ability-to-pay basis. Thereby, INNODIA.org is the interface between those who want to develop new therapies and those who have the expertise and tools to do so. 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. Furthermore, the tight collaboration of INNODIA HARVEST scientists across Europe has been a nucleus to extend the focus towards prediction and prevention in T1D within a new IHI consortium (EDENT1FI).
In summary, INNODIA HARVEST 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.
Besides the impact on people living with T1D, the INNODIA HARVEST clinical trial network supports pharmaceutical companies is developing new immunomodulatory therapies. To successfully develop those new drugs and therapy options, pharmaceutical companies rely on clinical expertise and effective infrastructures in Europe to successfully execute development plans, which we provided during INNODIA HARVEST. In addition, INNODIA HARVEST created a master protocol describing how new studies should be developed, allowing interim analysis and different interventions to be combined in a single trial. The aim is to gain more knowledge as quickly as possible about the effect of drugs and their impact on the progression of T1D in children, adolescents and adults. The established interim analyses helps to decide whether individual interventions or combinations of interventions are promising and whether it makes sense to pursue the approach further. This master protocol can be consulted for future trial designs by pharmaceutical companies or other stakeholders. 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. By doing so, 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. With these goals in mind, The INNODIA iVZW is established as a platform to access smart clinical trial expertise and data on an ability-to-pay basis. Thereby, INNODIA.org is the interface between those who want to develop new therapies and those who have the expertise and tools to do so. 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. Furthermore, the tight collaboration of INNODIA HARVEST scientists across Europe has been a nucleus to extend the focus towards prediction and prevention in T1D within a new IHI consortium (EDENT1FI).
In summary, INNODIA HARVEST 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.