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

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 fu...

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Vydané v:Current controlled trials in cardiovascular medicine Ročník 23; číslo 1; s. 414 - 9
Hlavní autori: Dunger, David B., Bruggraber, Sylvaine F. A., Mander, Adrian P., Marcovecchio, M. Loredana, Tree, Timothy, Chmura, Piotr Jaroslaw, Knip, Mikael, Schulte, Anke M., Mathieu, Chantal
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: London BioMed Central 18.05.2022
BioMed Central Ltd
Springer Nature B.V
BMC
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ISSN:1745-6215, 1745-6215
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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.
AbstractList 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.
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.
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. 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. 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.
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.BACKGROUNDThe 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.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.METHODSIn 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.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.DISCUSSIONThe 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.
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. 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. 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.
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
BackgroundThe 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.MethodsIn 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.DiscussionThe 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.
ArticleNumber 414
Audience Academic
Author Dunger, David B.
Marcovecchio, M. Loredana
Bruggraber, Sylvaine F. A.
Schulte, Anke M.
Mathieu, Chantal
Chmura, Piotr Jaroslaw
Knip, Mikael
Mander, Adrian P.
Tree, Timothy
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  fullname: Mander, Adrian P.
  organization: Centre for Trials Research, Cardiff University, NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London
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  organization: Centre for Trials Research, Cardiff University, NIHR Biomedical Research Centre, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London
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  surname: Chmura
  fullname: Chmura, Piotr Jaroslaw
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  organization: Pediatric Research Centre, Children’s Hospital, University of Helsinki and Helsinki University Hospital
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  organization: Department of Endocrinology, KU Leuven
BackLink https://www.ncbi.nlm.nih.gov/pubmed/35585600$$D View this record in MEDLINE/PubMed
https://hal.science/hal-04009896$$DView record in HAL
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ContentType Journal Article
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Knip, M
Nicolas, G
Veijola, R
Bovy, N
Dunger, D
Heller, S
Dayan, C
Dotta, F
Joner, G
Gillard, P
Pociot, F
Schloot, N
Speier, S
Wesley, J
Agiostratidou, G
Piel, B
Boitard, C
Tree, T
Datta, V
Lernmark, A
Cianfarani, S
Waldron-Lynch, F
Bonifacio, E
de Beaufort, C
Zaldumbide, A
Puthi, V
Otonkoski, T
Smith, A
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Dutta, S
Skrivarhaug, T
Alhadj Ali, M
Pieber, T
Napolitano-Rosen, A
Holl, R
Casteels, K
Evans, M
Scharfmann, R
Toppari, J
Ahmed, S
Hendriks, E
Mander, A
Cnop, M
Roep, B
Zac-Varghese, S
Ziegler, A G
Eizirik, D
Peakman, M
Anand, B
Mathieu, C
Rodriguez-Calvo, T
Nitsche, A
Jarosz-Chobot, P
Wallace, C
Hartmann, N
Ciampalini, P
Danne, T
Overbergh, L
Dias, R
Thankamony, A
Martin, F
Costecalde, G
Battelino, T
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Bosi, E
Mallone, R
von Herrath, M
Lundgren, M
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Strube, T
van Rampelbergh, J
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Lahesmaa, R
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Marchetti, P
Chiarelli, F
Patterson, C
Achenbach, P
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Goldfine, A
Richardson, S
Thorens, B
Wicker, L
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Issue 1
Keywords Prevention
Trials
Type 1 diabetes
Beta-cell function
C-peptide
Phase 2
Master protocol
Language English
License 2022. The Author(s).
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PublicationTitle Current controlled trials in cardiovascular medicine
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K Viele (6259_CR18) 2014; 13
A Hartemann (6259_CR7) 2013; 1
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CS Wilhelm-Benartzi (6259_CR14) 2021; 11
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Snippet Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from...
The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with...
Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from...
The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with...
BackgroundThe INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals...
Abstract Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from...
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StartPage 414
SubjectTerms Adolescent
Adult
Beneficiaries
Beta-cell function
Biomarkers
Biomedicine
C-peptide
Care and treatment
Charitable foundations
Child
Complications and side effects
COVID-19
Data integrity
Data warehouses
Decision making
Demographic aspects
Diabetes
Diabetes Mellitus, Type 1 - diagnosis
Diabetes Mellitus, Type 1 - drug therapy
Drug development
Health Sciences
Humans
Immunology
Laboratories
Life Sciences
Master protocol
Medicine
Medicine & Public Health
Medicine, Botanic
Medicine, Herbal
Natural history
Patient outcomes
Peptides
Phase 2
Prevention
SARS-CoV-2
Statistics for Life Sciences
Study Protocol
Teenagers
Treatment Outcome
Trials
Type 1 diabetes
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Title INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes
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