Minimum effective low dose of antithymocyte globulin in people aged 5-25 years with recent-onset stage 3 type 1 diabetes (MELD-ATG): a phase 2, multicentre, double-blind, randomised, placebo-controlled, adaptive dose-ranging trial
Type 1 diabetes remains an important health-care problem, with no disease-modifying therapies available in people with recent-onset, clinical type 1 diabetes. Adaptive trial designs, allowing faster evaluation of treatment modalities, remain underexplored in this stage of the disease. We aimed to id...
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| Vydáno v: | The Lancet (British edition) Ročník 406; číslo 10510; s. 1375 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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England
27.09.2025
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| ISSN: | 1474-547X, 1474-547X |
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| Abstract | Type 1 diabetes remains an important health-care problem, with no disease-modifying therapies available in people with recent-onset, clinical type 1 diabetes. Adaptive trial designs, allowing faster evaluation of treatment modalities, remain underexplored in this stage of the disease. We aimed to identify the minimum effective dose of antithymocyte globulin (ATG) in people aged 5-25 years with recent-onset, clinical type 1 diabetes.
MELD-ATG was a phase 2, double-blind, randomised, placebo-controlled, multi-arm, adaptive dose-ranging, parallel-cohort trial done in 14 accredited trial centres in eight countries (the UK, Denmark, Germany, Finland, Italy, Belgium, Austria, and Slovenia). Participants aged 5-25 years, diagnosed with clinical, stage 3 type 1 diabetes 3-9 weeks before treatment, with random C-peptide concentrations 0·2 nmol/L or more and at least one diabetes-related autoantibody (GADA, IA-2A, or ZnT8) were randomly assigned by a web-based randomisation system into seven consecutive cohorts receiving placebo, 2·5 mg/kg ATG, 1·5 mg/kg ATG, 0·5 mg/kg ATG, or 0·1 mg/kg ATG. Participants in cohort 1 were randomly assigned 1:1:1:1:1, participants in cohorts 2 and 3 were randomly assigned 1:1:1:1, and participants in cohorts 4-7 were randomly assigned 1:1:1. All cohorts included one placebo group and one 2·5 mg/kg ATG group. The other groups were assigned to ATG doses that were determined based on accruing data and the decision of the dose determining committee. The trial cohorts were stratified by age group (5-9 years, 10-17 years, and 18-25 years) with block sizes varying by cohort. Concealment lists, outlining the treatment allocation, were only available for the pharmacists; participants and study teams were masked to treatment allocation. ATG was administered by an intravenous infusion over 2 consecutive days. The primary outcome was the area under the curve (AUC) of the stimulated C-peptide concentration during a 2-h mixed-meal tolerance test at 12 months measured as ln(AUC C-peptide + 1). Conditional on finding a statistically significant difference at p<0·05 for 2·5 mg/kg ATG versus placebo, the minimum effective dose of ATG was determined. All randomly assigned participants were included in the primary analysis. All participants who received the study drug were included in the safety analysis. The trial was registered at ClinicalTrials.gov (NCT04509791) and is completed.
Between Nov 24, 2020, and Dec 13, 2023, 152 people were recruited and screened, 117 of whom were randomly assigned (placebo n=31, 0·1 mg/kg ATG n=6, 0·5 mg/kg ATG n=35, 1·5 mg/kg ATG n=12, and 2·5 mg/kg n=33). 54 (46%) of 117 participants were male and 63 (54%) were female. Participants were mainly European. The 0·1 mg/kg dose and the 1·5 mg/kg dose were progressively dropped from the study. At 12 months, the mean ln(AUC C-peptide + 1) was 0·411 nmol/L per min (SD 0·032) in the placebo group and 0·535 nmol/L per min (0·032) in the 2·5 mg/kg ATG group. The mean difference in the ln(AUC C-peptide + 1) between 2·5 mg/kg ATG and placebo was 0·124 nmol/L per min (95% CI 0·043-0·205; p=0·0028). At 12 months, the mean ln(AUC C-peptide + 1) in the 0·5 mg/kg ATG group, the remaining middle dose, was 0·513 nmol/L per min (SD 0·032), with a mean baseline-adjusted difference from placebo of 0·102 nmol/L per min (95% CI 0·021-0·183; p=0·014). Cytokine release syndrome occurred in 11 (33%) of 33 participants in the 2·5 mg/kg ATG group, eight (24%) of 34 in the 0·5mg/kg ATG group, and no participants in the placebo group. Serum sickness occurred in 27 (82%) participants in the 2·5 mg/kg ATG group, 11 (32%) in the 0·5 mg/kg ATG group, and no participants in the placebo group. There were no deaths related to adverse events.
In young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential of an affordable, repurposed agent, ATG, in a low and safe dose, as a disease-modifying agent in this population.
The European Union's Innovative Medicines Initiative 2 Joint Undertaking INNODIA. |
|---|---|
| AbstractList | Type 1 diabetes remains an important health-care problem, with no disease-modifying therapies available in people with recent-onset, clinical type 1 diabetes. Adaptive trial designs, allowing faster evaluation of treatment modalities, remain underexplored in this stage of the disease. We aimed to identify the minimum effective dose of antithymocyte globulin (ATG) in people aged 5-25 years with recent-onset, clinical type 1 diabetes.BACKGROUNDType 1 diabetes remains an important health-care problem, with no disease-modifying therapies available in people with recent-onset, clinical type 1 diabetes. Adaptive trial designs, allowing faster evaluation of treatment modalities, remain underexplored in this stage of the disease. We aimed to identify the minimum effective dose of antithymocyte globulin (ATG) in people aged 5-25 years with recent-onset, clinical type 1 diabetes.MELD-ATG was a phase 2, double-blind, randomised, placebo-controlled, multi-arm, adaptive dose-ranging, parallel-cohort trial done in 14 accredited trial centres in eight countries (the UK, Denmark, Germany, Finland, Italy, Belgium, Austria, and Slovenia). Participants aged 5-25 years, diagnosed with clinical, stage 3 type 1 diabetes 3-9 weeks before treatment, with random C-peptide concentrations 0·2 nmol/L or more and at least one diabetes-related autoantibody (GADA, IA-2A, or ZnT8) were randomly assigned by a web-based randomisation system into seven consecutive cohorts receiving placebo, 2·5 mg/kg ATG, 1·5 mg/kg ATG, 0·5 mg/kg ATG, or 0·1 mg/kg ATG. Participants in cohort 1 were randomly assigned 1:1:1:1:1, participants in cohorts 2 and 3 were randomly assigned 1:1:1:1, and participants in cohorts 4-7 were randomly assigned 1:1:1. All cohorts included one placebo group and one 2·5 mg/kg ATG group. The other groups were assigned to ATG doses that were determined based on accruing data and the decision of the dose determining committee. The trial cohorts were stratified by age group (5-9 years, 10-17 years, and 18-25 years) with block sizes varying by cohort. Concealment lists, outlining the treatment allocation, were only available for the pharmacists; participants and study teams were masked to treatment allocation. ATG was administered by an intravenous infusion over 2 consecutive days. The primary outcome was the area under the curve (AUC) of the stimulated C-peptide concentration during a 2-h mixed-meal tolerance test at 12 months measured as ln(AUC C-peptide + 1). Conditional on finding a statistically significant difference at p<0·05 for 2·5 mg/kg ATG versus placebo, the minimum effective dose of ATG was determined. All randomly assigned participants were included in the primary analysis. All participants who received the study drug were included in the safety analysis. The trial was registered at ClinicalTrials.gov (NCT04509791) and is completed.METHODSMELD-ATG was a phase 2, double-blind, randomised, placebo-controlled, multi-arm, adaptive dose-ranging, parallel-cohort trial done in 14 accredited trial centres in eight countries (the UK, Denmark, Germany, Finland, Italy, Belgium, Austria, and Slovenia). Participants aged 5-25 years, diagnosed with clinical, stage 3 type 1 diabetes 3-9 weeks before treatment, with random C-peptide concentrations 0·2 nmol/L or more and at least one diabetes-related autoantibody (GADA, IA-2A, or ZnT8) were randomly assigned by a web-based randomisation system into seven consecutive cohorts receiving placebo, 2·5 mg/kg ATG, 1·5 mg/kg ATG, 0·5 mg/kg ATG, or 0·1 mg/kg ATG. Participants in cohort 1 were randomly assigned 1:1:1:1:1, participants in cohorts 2 and 3 were randomly assigned 1:1:1:1, and participants in cohorts 4-7 were randomly assigned 1:1:1. All cohorts included one placebo group and one 2·5 mg/kg ATG group. The other groups were assigned to ATG doses that were determined based on accruing data and the decision of the dose determining committee. The trial cohorts were stratified by age group (5-9 years, 10-17 years, and 18-25 years) with block sizes varying by cohort. Concealment lists, outlining the treatment allocation, were only available for the pharmacists; participants and study teams were masked to treatment allocation. ATG was administered by an intravenous infusion over 2 consecutive days. The primary outcome was the area under the curve (AUC) of the stimulated C-peptide concentration during a 2-h mixed-meal tolerance test at 12 months measured as ln(AUC C-peptide + 1). Conditional on finding a statistically significant difference at p<0·05 for 2·5 mg/kg ATG versus placebo, the minimum effective dose of ATG was determined. All randomly assigned participants were included in the primary analysis. All participants who received the study drug were included in the safety analysis. The trial was registered at ClinicalTrials.gov (NCT04509791) and is completed.Between Nov 24, 2020, and Dec 13, 2023, 152 people were recruited and screened, 117 of whom were randomly assigned (placebo n=31, 0·1 mg/kg ATG n=6, 0·5 mg/kg ATG n=35, 1·5 mg/kg ATG n=12, and 2·5 mg/kg n=33). 54 (46%) of 117 participants were male and 63 (54%) were female. Participants were mainly European. The 0·1 mg/kg dose and the 1·5 mg/kg dose were progressively dropped from the study. At 12 months, the mean ln(AUC C-peptide + 1) was 0·411 nmol/L per min (SD 0·032) in the placebo group and 0·535 nmol/L per min (0·032) in the 2·5 mg/kg ATG group. The mean difference in the ln(AUC C-peptide + 1) between 2·5 mg/kg ATG and placebo was 0·124 nmol/L per min (95% CI 0·043-0·205; p=0·0028). At 12 months, the mean ln(AUC C-peptide + 1) in the 0·5 mg/kg ATG group, the remaining middle dose, was 0·513 nmol/L per min (SD 0·032), with a mean baseline-adjusted difference from placebo of 0·102 nmol/L per min (95% CI 0·021-0·183; p=0·014). Cytokine release syndrome occurred in 11 (33%) of 33 participants in the 2·5 mg/kg ATG group, eight (24%) of 34 in the 0·5mg/kg ATG group, and no participants in the placebo group. Serum sickness occurred in 27 (82%) participants in the 2·5 mg/kg ATG group, 11 (32%) in the 0·5 mg/kg ATG group, and no participants in the placebo group. There were no deaths related to adverse events.FINDINGSBetween Nov 24, 2020, and Dec 13, 2023, 152 people were recruited and screened, 117 of whom were randomly assigned (placebo n=31, 0·1 mg/kg ATG n=6, 0·5 mg/kg ATG n=35, 1·5 mg/kg ATG n=12, and 2·5 mg/kg n=33). 54 (46%) of 117 participants were male and 63 (54%) were female. Participants were mainly European. The 0·1 mg/kg dose and the 1·5 mg/kg dose were progressively dropped from the study. At 12 months, the mean ln(AUC C-peptide + 1) was 0·411 nmol/L per min (SD 0·032) in the placebo group and 0·535 nmol/L per min (0·032) in the 2·5 mg/kg ATG group. The mean difference in the ln(AUC C-peptide + 1) between 2·5 mg/kg ATG and placebo was 0·124 nmol/L per min (95% CI 0·043-0·205; p=0·0028). At 12 months, the mean ln(AUC C-peptide + 1) in the 0·5 mg/kg ATG group, the remaining middle dose, was 0·513 nmol/L per min (SD 0·032), with a mean baseline-adjusted difference from placebo of 0·102 nmol/L per min (95% CI 0·021-0·183; p=0·014). Cytokine release syndrome occurred in 11 (33%) of 33 participants in the 2·5 mg/kg ATG group, eight (24%) of 34 in the 0·5mg/kg ATG group, and no participants in the placebo group. Serum sickness occurred in 27 (82%) participants in the 2·5 mg/kg ATG group, 11 (32%) in the 0·5 mg/kg ATG group, and no participants in the placebo group. There were no deaths related to adverse events.In young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential of an affordable, repurposed agent, ATG, in a low and safe dose, as a disease-modifying agent in this population.INTERPRETATIONIn young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential of an affordable, repurposed agent, ATG, in a low and safe dose, as a disease-modifying agent in this population.The European Union's Innovative Medicines Initiative 2 Joint Undertaking INNODIA.FUNDINGThe European Union's Innovative Medicines Initiative 2 Joint Undertaking INNODIA. Type 1 diabetes remains an important health-care problem, with no disease-modifying therapies available in people with recent-onset, clinical type 1 diabetes. Adaptive trial designs, allowing faster evaluation of treatment modalities, remain underexplored in this stage of the disease. We aimed to identify the minimum effective dose of antithymocyte globulin (ATG) in people aged 5-25 years with recent-onset, clinical type 1 diabetes. MELD-ATG was a phase 2, double-blind, randomised, placebo-controlled, multi-arm, adaptive dose-ranging, parallel-cohort trial done in 14 accredited trial centres in eight countries (the UK, Denmark, Germany, Finland, Italy, Belgium, Austria, and Slovenia). Participants aged 5-25 years, diagnosed with clinical, stage 3 type 1 diabetes 3-9 weeks before treatment, with random C-peptide concentrations 0·2 nmol/L or more and at least one diabetes-related autoantibody (GADA, IA-2A, or ZnT8) were randomly assigned by a web-based randomisation system into seven consecutive cohorts receiving placebo, 2·5 mg/kg ATG, 1·5 mg/kg ATG, 0·5 mg/kg ATG, or 0·1 mg/kg ATG. Participants in cohort 1 were randomly assigned 1:1:1:1:1, participants in cohorts 2 and 3 were randomly assigned 1:1:1:1, and participants in cohorts 4-7 were randomly assigned 1:1:1. All cohorts included one placebo group and one 2·5 mg/kg ATG group. The other groups were assigned to ATG doses that were determined based on accruing data and the decision of the dose determining committee. The trial cohorts were stratified by age group (5-9 years, 10-17 years, and 18-25 years) with block sizes varying by cohort. Concealment lists, outlining the treatment allocation, were only available for the pharmacists; participants and study teams were masked to treatment allocation. ATG was administered by an intravenous infusion over 2 consecutive days. The primary outcome was the area under the curve (AUC) of the stimulated C-peptide concentration during a 2-h mixed-meal tolerance test at 12 months measured as ln(AUC C-peptide + 1). Conditional on finding a statistically significant difference at p<0·05 for 2·5 mg/kg ATG versus placebo, the minimum effective dose of ATG was determined. All randomly assigned participants were included in the primary analysis. All participants who received the study drug were included in the safety analysis. The trial was registered at ClinicalTrials.gov (NCT04509791) and is completed. Between Nov 24, 2020, and Dec 13, 2023, 152 people were recruited and screened, 117 of whom were randomly assigned (placebo n=31, 0·1 mg/kg ATG n=6, 0·5 mg/kg ATG n=35, 1·5 mg/kg ATG n=12, and 2·5 mg/kg n=33). 54 (46%) of 117 participants were male and 63 (54%) were female. Participants were mainly European. The 0·1 mg/kg dose and the 1·5 mg/kg dose were progressively dropped from the study. At 12 months, the mean ln(AUC C-peptide + 1) was 0·411 nmol/L per min (SD 0·032) in the placebo group and 0·535 nmol/L per min (0·032) in the 2·5 mg/kg ATG group. The mean difference in the ln(AUC C-peptide + 1) between 2·5 mg/kg ATG and placebo was 0·124 nmol/L per min (95% CI 0·043-0·205; p=0·0028). At 12 months, the mean ln(AUC C-peptide + 1) in the 0·5 mg/kg ATG group, the remaining middle dose, was 0·513 nmol/L per min (SD 0·032), with a mean baseline-adjusted difference from placebo of 0·102 nmol/L per min (95% CI 0·021-0·183; p=0·014). Cytokine release syndrome occurred in 11 (33%) of 33 participants in the 2·5 mg/kg ATG group, eight (24%) of 34 in the 0·5mg/kg ATG group, and no participants in the placebo group. Serum sickness occurred in 27 (82%) participants in the 2·5 mg/kg ATG group, 11 (32%) in the 0·5 mg/kg ATG group, and no participants in the placebo group. There were no deaths related to adverse events. In young people with recent-onset, clinical type 1 diabetes, 2·5 mg/kg and 0·5 mg/kg ATG reduced loss of β-cell function, showing the potential of an affordable, repurposed agent, ATG, in a low and safe dose, as a disease-modifying agent in this population. The European Union's Innovative Medicines Initiative 2 Joint Undertaking INNODIA. |
| Author | Evans, Mark Johannesen, Jesper De Block, Christophe Gillespie, David Hendriks, A Emile J Overbergh, Lut Möller, Christopher Pulkkinen, Mari-Anne Mander, Adrian P Wilhelm-Benartzi, Charlotte Casteels, Kristina Wych, Julie Battelino, Tadej Cnop, Miriam Marcovecchio, M Loredana Niemöller, Elisabeth Pieber, Thomas Chmura, Piotr Peakman, Mark Basu, Supriyo Tree, Timothy Rami-Merhar, Birgit Willemsen, Ruben H Hilbrands, Robert Knip, Mikael Nitsche, Almut Danne, Thomas Reschke, Felix Šmigoc Schweiger, Darja Van Ryckeghem, Lisa Schulte, Anke M Mathieu, Chantal Bosi, Emanuele |
| Author_xml | – sequence: 1 givenname: Chantal surname: Mathieu fullname: Mathieu, Chantal email: chantal.mathieu@uzleuven.be organization: Department of Endocrinology, UZ Gasthuisberg, UZ Leuven, Leuven, Belgium; Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium. Electronic address: chantal.mathieu@uzleuven.be – sequence: 2 givenname: Julie surname: Wych fullname: Wych, Julie organization: Centre for Trials Research College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK – sequence: 3 givenname: A Emile J surname: Hendriks fullname: Hendriks, A Emile J organization: Department of Paediatrics, University of Cambridge, Cambridge, UK; Department of Paediatric Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK – sequence: 4 givenname: Lisa surname: Van Ryckeghem fullname: Van Ryckeghem, Lisa organization: Department of Endocrinology, UZ Gasthuisberg, UZ Leuven, Leuven, Belgium – sequence: 5 givenname: Timothy surname: Tree fullname: Tree, Timothy organization: Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK – sequence: 6 givenname: Piotr surname: Chmura fullname: Chmura, Piotr organization: Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark – sequence: 7 givenname: Christopher surname: Möller fullname: Möller, Christopher organization: Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark – sequence: 8 givenname: Kristina surname: Casteels fullname: Casteels, Kristina organization: Department of Paediatrics, UZ Gasthuisberg, UZ Leuven, Leuven, Belgium – sequence: 9 givenname: Thomas surname: Danne fullname: Danne, Thomas organization: Center for Paediatric Endocrinology, Diabetology, and Clinical Research, Auf Der Bult Children's Hospital, Hannover, Germany – sequence: 10 givenname: Felix surname: Reschke fullname: Reschke, Felix organization: Center for Paediatric Endocrinology, Diabetology, and Clinical Research, Auf Der Bult Children's Hospital, Hannover, Germany – sequence: 11 givenname: Darja surname: Šmigoc Schweiger fullname: Šmigoc Schweiger, Darja organization: Department of Endocrinology, Diabetes, and Metabolic Diseases, University Children's Hospital, University Medical Center Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia – sequence: 12 givenname: Tadej surname: Battelino fullname: Battelino, Tadej organization: Department of Endocrinology, Diabetes, and Metabolic Diseases, University Children's Hospital, University Medical Center Ljubljana, Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia – sequence: 13 givenname: Jesper surname: Johannesen fullname: Johannesen, Jesper organization: Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Copenhagen University Hospital Herlev, Department of Paediatrics, Copenhagen, Denmark; Steno Diabetes Center, Copenhagen, Denmark – sequence: 14 givenname: Birgit surname: Rami-Merhar fullname: Rami-Merhar, Birgit organization: Department of Paediatric and Adolescent Medicine, Division of Paediatric Pulmonology, Allergology, and Endocrinology, Comprehensive Centre for Paediatrics, Medical University of Vienna, Vienna, Austria – sequence: 15 givenname: Thomas surname: Pieber fullname: Pieber, Thomas organization: Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria – sequence: 16 givenname: Christophe surname: De Block fullname: De Block, Christophe organization: Department of Endocrinology-Diabetology-Metabolism, Antwerp University Hospital and University of Antwerp, Antwerp, Belgium – sequence: 17 givenname: Mark surname: Evans fullname: Evans, Mark organization: Institute of Metabolic Science and Department of Medicine, University of Cambridge, Cambridge, UK – sequence: 18 givenname: Robert surname: Hilbrands fullname: Hilbrands, Robert organization: Academic Hospital and Diabetes Research Centre, Vrije Universiteit Brussels, Brussels, Belgium – sequence: 19 givenname: Emanuele surname: Bosi fullname: Bosi, Emanuele organization: Diabetes Research Institute San Raffaele Hospital and San Raffaele Vita Salute University, Milan, Italy – sequence: 20 givenname: Ruben H surname: Willemsen fullname: Willemsen, Ruben H organization: Department of Paediatric Diabetes and Endocrinology, The Royal London Children's hospital, Barts Health NHS Trust, London, UK – sequence: 21 givenname: Supriyo surname: Basu fullname: Basu, Supriyo organization: Department of Paediatric Endocrinology and Diabetes, Oxford University Hospitals NHS Foundation Trust, Oxford, UK – sequence: 22 givenname: Mari-Anne surname: Pulkkinen fullname: Pulkkinen, Mari-Anne organization: New Children's Hospital, Paediatric Research Centre, Helsinki University Hospital and Faculty of Medicine, University of Helsinki, Helsinki, Finland – sequence: 23 givenname: Mikael surname: Knip fullname: Knip, Mikael organization: Research Program for Clinical and Molecular Metabolism, University of Helsinki, Helsinki, Finland – sequence: 24 givenname: Miriam surname: Cnop fullname: Cnop, Miriam organization: ULB Center for Diabetes Research, Université Libre de Bruxelles, Brussels, Belgium; Division of Endocrinology, ULB Erasmus Hospital, Brussels University Hospital, Université Libre de Bruxelles, Brussels, Belgium – sequence: 25 givenname: Almut surname: Nitsche fullname: Nitsche, Almut organization: Diabetes Cardiovascular Metabolic Development, Research and Development, Sanofi-Deutschland, Frankfurt, Germany – sequence: 26 givenname: Anke M surname: Schulte fullname: Schulte, Anke M organization: Diabetes Cardiovascular Metabolic Development, Research and Development, Sanofi-Deutschland, Frankfurt, Germany – sequence: 27 givenname: Elisabeth surname: Niemöller fullname: Niemöller, Elisabeth organization: Diabetes Cardiovascular Metabolic Development, Research and Development, Sanofi-Deutschland, Frankfurt, Germany – sequence: 28 givenname: Mark surname: Peakman fullname: Peakman, Mark organization: Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, London, UK; Sanofi Research and Development, Paris, France – sequence: 29 givenname: Charlotte surname: Wilhelm-Benartzi fullname: Wilhelm-Benartzi, Charlotte organization: Centre for Trials Research College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK – sequence: 30 givenname: David surname: Gillespie fullname: Gillespie, David organization: Centre for Trials Research College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK – sequence: 31 givenname: Lut surname: Overbergh fullname: Overbergh, Lut organization: Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium – sequence: 32 givenname: Adrian P surname: Mander fullname: Mander, Adrian P organization: Centre for Trials Research College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK – sequence: 33 givenname: M Loredana surname: Marcovecchio fullname: Marcovecchio, M Loredana organization: Department of Paediatrics, University of Cambridge, Cambridge, UK; Department of Paediatric Diabetes and Endocrinology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40976248$$D View this record in MEDLINE/PubMed |
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| CitedBy_id | crossref_primary_10_1016_S0140_6736_25_01438_2 |
| ContentType | Journal Article |
| Contributor | Evans, Mark Bonifacio, Ezio Morgan, Noel G Dayan, Colin M Agiostratidou, Gina Wicker, Linda Marchetti, Piero Pociot, Flemming Mander, Adrian P Holl, Reinhard Cnop, Miriam Battelino, Tadej Keil, Stefanie Marcovecchio, M Loredana Ziegler, Anette G Brunak, Søren Lundgren, Markus Tree, Timothy Otonkoski, Timo Koralova, Anne Knip, Mikael Roep, Bart O Todd, John A Gotthardt, Martin Johannesen, Jesper Gillespie, David Hendriks, A Emile J Dahl-Jørgensen, Knut Overbergh, Lutgart von Herrath, Matthias Cianfarani, Stefano Wych, Julie Niemöller, Elisabeth Pieber, Thomas Chiarelli, Francesco Peakman, Mark Veijola, Riitta Mallone, Roberto Lahesmaa, Riitta Dutta, Sanjoy Costecalde, Guillaume Dotta, Francesco Solimena, Michele Latres, Esther Jarosz-Chobot, Przemyslawa Napolitano-Rosen, Antonella de Beaufort, Carine Eizirik, Decio L Mathieu, Chantal Bosi, Emanuele |
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| Copyright | 2025 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies. |
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| Snippet | Type 1 diabetes remains an important health-care problem, with no disease-modifying therapies available in people with recent-onset, clinical type 1 diabetes.... |
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| SubjectTerms | Adolescent Adult Antilymphocyte Serum - administration & dosage Antilymphocyte Serum - adverse effects Child Child, Preschool Diabetes Mellitus, Type 1 - drug therapy Dose-Response Relationship, Drug Double-Blind Method Female Humans Immunosuppressive Agents - administration & dosage Male Treatment Outcome Young Adult |
| Title | Minimum effective low dose of antithymocyte globulin in people aged 5-25 years with recent-onset stage 3 type 1 diabetes (MELD-ATG): a phase 2, multicentre, double-blind, randomised, placebo-controlled, adaptive dose-ranging trial |
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