Curtin Francois, Champion Bernard, Davoren Peter, Duke Sally, Ekinci Elif I, Gilfillan Chris, Morbey Claire, Nathow Thomas, O'Moore-Sullivan Trisha, O'Neal David, Roberts Adam, Stranks Stephen, Stuckey Bronwyn, Vora Parind, Malpass Sam, Lloyd David, Maëstracci-Beard Nicole, Buffet Bénédicte, Kornmann Gabrielle, Bernard Corinne, Porchet Hervé, Simpson Richard
GeNeuro SA, Geneva, Switzerland.
Division of Clinical Pharmacology and Toxicology, Rue Perret-Gentil, University of Geneva, Geneva, Switzerland.
Diabetes Obes Metab. 2020 Jul;22(7):1111-1121. doi: 10.1111/dom.14010. Epub 2020 Mar 12.
To report the first study of temelimab, a monoclonal antibody neutralizing the pathogenic human endogenous retrovirus type W envelope, in patients with type 1 diabetes (T1D).
This double-blind, placebo-controlled, randomized clinical trial recruited adult patients with T1D within 4 years postdiagnosis and remaining C-peptide secretion. Sixty-four patients were randomized (2:1) to monthly temelimab 6 mg/kg or placebo during 24 weeks followed by a 24-week, open-label extension, during which all patients received temelimab. The primary objective was the safety and tolerability of temelimab. The secondary objective was to assess the pharmacodynamics response such as C-peptide levels, insulin use, HbA1c, hypoglycaemia and autoantibodies.
Temelimab was well tolerated without any group difference in the frequency or severity of adverse events. Concerning exploratory endpoints, there was no difference in the levels of C-peptide, insulin use or HbA1c between treatment groups at weeks 24 and 48. The frequency of hypoglycaemia events was reduced with temelimab (P = 0.0004) at week 24 and the level of anti-insulin antibodies was lower with temelimab (P < 0.01); the other autoantibodies did not differ between groups.
Temelimab appeared safe in patients with T1D. Pharmacodynamics signals (hypoglycaemia and anti-insulin antibodies) under temelimab were observed. Markers of β-cell functions were not modified by treatment. These results need to be further explored in younger patients with T1D with earlier disease onset.
报告首次在1型糖尿病（T1D）患者中使用替美单抗（一种中和致病性人类内源性逆转录病毒W型包膜的单克隆抗体）的研究。
这项双盲、安慰剂对照、随机临床试验招募了诊断后4年内且仍有C肽分泌的成年T1D患者。64名患者被随机分组（2:1），在24周内每月接受6 mg/kg替美单抗或安慰剂治疗，随后进行为期24周的开放标签扩展期，在此期间所有患者均接受替美单抗治疗。主要目标是替美单抗的安全性和耐受性。次要目标是评估药效学反应，如C肽水平、胰岛素使用情况、糖化血红蛋白（HbA1c）、低血糖和自身抗体。
替美单抗耐受性良好，不良事件的频率或严重程度在各组之间无差异。关于探索性终点，在第24周和第48周时，治疗组之间的C肽水平、胰岛素使用情况或HbA1c没有差异。在第24周时，替美单抗治疗可降低低血糖事件的发生率（P = 0.0004），且替美单抗治疗组的抗胰岛素抗体水平较低（P < 0.01）；其他自身抗体在各组之间无差异。
替美单抗在T1D患者中似乎是安全的。观察到替美单抗治疗下的药效学信号（低血糖和抗胰岛素抗体）。治疗未改变β细胞功能标志物。这些结果需要在疾病发病更早的年轻T1D患者中进一步探索。
