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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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cam.depositDate2021-12-03
cam.issuedOnline2021-12-07
cam.orpheus.counter7
cam.orpheus.success2022-06-01: VoR added, publication date updated
dc.contributor.authorMarcovecchio, Maria Loredana
dc.contributor.authorWilhelm-Benartzi, Charlotte S
dc.contributor.authorMiller, Sarah E
dc.contributor.authorBruggraber, Sylvaine
dc.contributor.authorPicton, Diane
dc.contributor.authorWilson, Mark
dc.contributor.authorGatley, Katrina
dc.contributor.authorChhabra, Anita
dc.contributor.authorHendriks, A Emile J
dc.contributor.authorMorobé, Hilde
dc.contributor.authorChmura, Piotr Jaroslaw Chmura
dc.contributor.authorBond, Simon
dc.contributor.authorAschemeier-Fuchs, Bärbel
dc.contributor.authorKnip, Mikael
dc.contributor.authorTree, Tim
dc.contributor.authorOverbergh, Lut
dc.contributor.authorPall, Jaivier
dc.contributor.authorArnaud, Olivier
dc.contributor.authorHaller, Michael J
dc.contributor.authorNitsche, Almut
dc.contributor.authorSchulte, Anke M
dc.contributor.authorMathieu, Chantal
dc.contributor.authorMander, Adrian
dc.contributor.authorDunger, David B
dc.contributor.orcidMarcovecchio, Loredana [0000-0002-4415-316X]
dc.contributor.orcidHendriks, Emile [0000-0002-0795-1832]
dc.contributor.orcidBond, Simon [0000-0003-2528-1040]
dc.date.accessioned2021-12-07T00:30:25Z
dc.date.available2021-12-07T00:30:25Z
dc.date.updated2021-12-03T14:38:27Z
dc.description.abstract• 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 ATG, Thymoglobuline®, encouraging further exploration in lower age groups. Methods and analysis: MELD-ATG is a phase 2, multi-centre, randomised, double-blind, placebo-controlled, multi-arm 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 2 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 (MMTT) at 12 months for 2.5mg/kg ATG arm versus 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) HbA1c, 3) daily insulin dose, 4) time in range by intermittent continuous glucose monitoring (CGM) 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 grant agreement (www.innodia.eu).
dc.description.sponsorshipUnion’s Horizon 2020 research and innovation program EFPIA JDRF The Leona M. and Harry B. Helmsley Charitable Trust
dc.identifier.doi10.17863/CAM.78688
dc.identifier.issn2044-6055
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/331243
dc.language.isoeng
dc.publisherBMJ Journals
dc.publisher.departmentDepartment of Paediatrics
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleStudy 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
dc.typeArticle
dcterms.dateAccepted2021-11-08
prism.publicationNameBMJ Open
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
pubs.licence-identifierapollo-deposit-licence-2-1
rioxxterms.typeJournal Article/Review
rioxxterms.versionVoR
rioxxterms.versionofrecord10.1136/bmjopen-2021-053669

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