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Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes.

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العنوان: Study protocol: Minimum effective low dose: anti-human thymocyte globulin (MELD-ATG): phase II, dose ranging, efficacy study of antithymocyte globulin (ATG) within 6 weeks of diagnosis of type 1 diabetes.
المؤلفون: Wilhelm-Benartzi CS; Centre for Trials Research, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK Wilhelm-BenartziC@cardiff.ac.uk., Miller SE; Department of Paediatrics, University of Cambridge, Cambridge, UK.; Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Bruggraber S; Department of Paediatrics, University of Cambridge, Cambridge, UK., Picton D; Department of Paediatrics, University of Cambridge, Cambridge, UK., Wilson M; Department of Paediatrics, University of Cambridge, Cambridge, UK., Gatley K; Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Chhabra A; Pharmacy, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Marcovecchio ML; Department of Paediatrics, University of Cambridge, Cambridge, UK., Hendriks AEJ; Department of Paediatrics, University of Cambridge, Cambridge, UK., Morobé H; Katholieke Universiteit Leuven/ Universitaire Ziekenhuizen, Leuven, Belgium., Chmura PJ; Center for Protein Research, Kobenhavns Universitet Sundhedsvidenskabelige Fakultet, Kobenhavn, Denmark., Bond S; Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Aschemeier-Fuchs B; Diabetes Centre for Children and Adolescents, Children's Hospital Auf der Bult, Hannover, Germany., Knip M; Research Program for Clinical and Molecular Metabolism, University of Helsinki Faculty of Medicine, Helsinki, Finland.; Pediatric Research Centre, University of Helsinki Children's Hospital, Helsinki, Finland., Tree T; Department of Immunobiology, King's College London, London, UK., Overbergh L; Katholieke Universiteit Leuven/ Universitaire Ziekenhuizen, Leuven, Belgium., Pall J; INNODIA Patient Advisory Committee, Madrid, Spain., Arnaud O; INNODIA Patient Advisory Committee, Paris, France., Haller MJ; Department of Pediatrics, University of Florida, Gainesville, Florida, USA., Nitsche A; Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany., Schulte AM; Sanofi-Aventis Deutschland GmbH, Frankfurt, Germany., Mathieu C; Katholieke Universiteit Leuven/ Universitaire Ziekenhuizen, Leuven, Belgium., Mander A; Centre for Trials Research, College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK., Dunger D; Department of Paediatrics, University of Cambridge, Cambridge, UK.; Wellcome Trust-MRC Institute of Metabolic Science, Cambridge University, Cambridge, UK.
المصدر: BMJ open [BMJ Open] 2021 Dec 07; Vol. 11 (12), pp. e053669. Date of Electronic Publication: 2021 Dec 07.
نوع المنشور: Clinical Trial Protocol; Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : BMJ Publishing Group Ltd, 2011-
مواضيع طبية MeSH: Diabetes Mellitus, Type 1*/drug therapy, Adolescent ; Adult ; Antilymphocyte Serum/therapeutic use ; Blood Glucose ; Blood Glucose Self-Monitoring ; Child ; Clinical Trials, Phase II as Topic ; Humans ; Middle Aged ; Multicenter Studies as Topic ; Randomized Controlled Trials as Topic ; Thymocytes ; Treatment Outcome ; Young Adult
مستخلص: Introduction: Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing β cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is antithymocyte globulin (ATG), Thymoglobuline, encouraging further exploration in lower age groups.
Methods and Analysis: Minimal effective low dose (MELD)-ATG is a phase 2, multicentre, randomised, double-blind, placebo-controlled, multiarm parallel-group trial in participants 5-25 years diagnosed with T1D within 3-9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12-15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over two consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test at 12 months for 2.5 mg/kg ATG arm vs the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on (1) stimulated C-peptide, (2) glycated haemoglobin, (3) daily insulin dose, (4) time in range by intermittent continuous glucose monitoring measures, (5) fasting and stimulated dry blood spot (DBS) C-peptide measurements.
Ethics and Dissemination: MELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA (An innovative approach towards understanding and arresting Type 1 diabetes consortium) grant agreement (www.innodia.eu).
Trial Registration Number: NCT03936634; Pre-results.
Competing Interests: Competing interests: CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp and Dohme, Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma. Financial compensation for these activities has been received by KU Leuven; KU Leuven has received research support for CM from Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics; CM serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, Astra Zeneca and Novartis. Financial compensation for these activities has been received by KU Leuven. MJH is a scientific board member of SAbBiotherapeutics and has received research funding from Sanofi. AN and AMS are Sanofi employees and may hold shares and/or stock options in the company.
(© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)
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فهرسة مساهمة: Keywords: general diabetes; paediatric endocrinology; statistics & research methods
سلسلة جزيئية: ClinicalTrials.gov NCT03936634
المشرفين على المادة: 0 (Antilymphocyte Serum)
0 (Blood Glucose)
تواريخ الأحداث: Date Created: 20211208 Date Completed: 20220307 Latest Revision: 20220307
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8655536
DOI: 10.1136/bmjopen-2021-053669
PMID: 34876434
قاعدة البيانات: MEDLINE
الوصف
تدمد:2044-6055
DOI:10.1136/bmjopen-2021-053669