First-in-human, double-blind, randomized phase 1b study of peptide immunotherapy IMCY-0098 in new-onset type 1 diabetes

BMC Medicine

Research Article

Martin Kindermans¹  Frédéric Parmentier¹  Richard David Leslie²  Mohammad Alhadj Ali³  Colin Dayan³  Luc Vanderelst⁴  Nicolas Bovy⁴  Pierre Vandepapelière⁴  Marcelle Van Mechelen⁴  Vincent Carlier⁴  Evelien Gebruers⁴  Roxana R. Ahangarani⁴  Jean Van Rampelbergh⁴  Christian Boitard⁵  Peter Achenbach⁶  Bart Keymeulen⁷  Katharine R. Owen⁸ 

[1] Ariana Pharmaceuticals SA, Paris, France;Department of Immunobiology, Queen Mary University of London, London, UK;Diabetes Research Group, Cardiff University School of Medicine, Cardiff University, Cardiff, UK;Imcyse S.A., Avenue Pré-Aily 14, Angleur, 4031, Liège, Belgium;Inserm U1016, Cochin Institute, Paris, France;Medical Faculty, Université de Paris, Paris, France;Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany;Forschergruppe Diabetes, Technical University Munich, Klinikum Rechts Der Isar, Munich, Germany;Member of Belgian Diabetes Registry, Academic Hospital and Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium;Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK;Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, UK;

关键词: Type 1 diabetes;    Immunotherapy;    T cells;    Beta-cells;    Clinical study;    Safety;   

DOI  :  10.1186/s12916-023-02900-z

 received in 2022-01-17, accepted in 2023-05-10,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundType 1 diabetes (T1D) is a CD4+ T cell-driven autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells by CD8+ T cells. Achieving glycemic targets in T1D remains challenging in clinical practice; new treatments aim to halt autoimmunity and prolong β-cell survival. IMCY-0098 is a peptide derived from human proinsulin that contains a thiol-disulfide oxidoreductase motif at the N-terminus and was developed to halt disease progression by promoting the specific elimination of pathogenic T cells.MethodsThis first-in-human, 24-week, double-blind phase 1b study evaluated the safety of three dosages of IMCY-0098 in adults diagnosed with T1D < 6 months before study start. Forty-one participants were randomized to receive four bi-weekly injections of placebo or increasing doses of IMCY-0098 (dose groups A/B/C received 50/150/450 μg for priming followed by three further administrations of 25/75/225 μg, respectively). Multiple T1D-related clinical parameters were also assessed to monitor disease progression and inform future development. Long-term follow-up to 48 weeks was also conducted in a subset of patients.ResultsTreatment with IMCY-0098 was well tolerated with no systemic reactions; a total of 315 adverse events (AEs) were reported in 40 patients (97.6%) and were related to study treatment in 29 patients (68.3%). AEs were generally mild; no AE led to discontinuation of the study or death. No significant decline in C-peptide was noted from baseline to Week 24 for dose A, B, C, or placebo (mean change − 0.108, − 0.041, − 0.040, and − 0.012, respectively), suggesting no disease progression.ConclusionsPromising safety profile and preliminary clinical response data support the design of a phase 2 study of IMCY-0098 in patients with recent-onset T1D.Trial registrationIMCY-T1D-001: ClinicalTrials.gov NCT03272269; EudraCT: 2016–003514-27; and IMCY-T1D-002: ClinicalTrials.gov NCT04190693; EudraCT: 2018–003728-35.

【 授权许可】

CC BY   
© The Author(s) 2023

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