Krausz Máté, Uhlmann Annette, Rump Ina Caroline, Ihorst Gabriele, Goldacker Sigune, Sogkas Georgios, Posadas-Cantera Sara, Schmidt Reinhold, Feißt Manuel, Alsina Laia, Dybedal Ingunn, Recher Mike, Warnatz Klaus, Grimbacher Bodo
Department of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Hugstetter Straße 55, 79106 Freiburg, Germany.
Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI), Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Breisacher Straße 115, 79106 Freiburg, Germany.
Contemp Clin Trials Commun. 2022 Sep 24;30:101008. doi: 10.1016/j.conctc.2022.101008. eCollection 2022 Dec.
Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) insufficiency and lipopolysaccharide-responsive and beige-like anchor protein (LRBA) deficiency are both complex immune dysregulation syndromes with an underlying regulatory T cell dysfunction due to the lack of CTLA-4 protein. As anticipated, the clinical phenotypes of CTLA-4 insufficiency and LRBA deficiency are similar. Main manifestations include hypogammaglobulinemia, lymphoproliferation, autoimmune cytopenia, immune-mediated respiratory, gastrointestinal, neurological, and skin involvement, which can be severe and disabling. The rationale of this clinical trial is to improve clinical outcomes of affected patients by substituting the deficient CTLA-4 by administration of CTLA4-Ig (abatacept) as a causative personalized treatment.
Our objective is to assess the safety and efficacy of abatacept for patients with CTLA-4 insufficiency or LRBA deficiency. The study will also investigate how treatment with abatacept affects the patients' quality of life.
/Design: ABACHAI is a phase IIa prospective, non-randomized, open-label, single arm multi-center trial. Altogether 20 adult patients will be treated with abatacept 125 mg s.c. on a weekly basis for 12 months, including (1) patients already pretreated with abatacept, and (2) patients not pretreated, starting with abatacept therapy at the baseline study visit. For the evaluation of drug safety infection control during the trial, for efficacy, the CHAI-Morbidity Score will be used.
The trial is registered in the German Clinical Trials Register (Deutsches Register Klinischer Studien, DRKS) with the identity number DRKS00017736, registered: 6 July 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017736.
细胞毒性T淋巴细胞相关蛋白4（CTLA-4）功能不全和脂多糖反应性及米色样锚定蛋白（LRBA）缺乏都是复杂的免疫失调综合征，由于缺乏CTLA-4蛋白，存在潜在的调节性T细胞功能障碍。正如预期的那样，CTLA-4功能不全和LRBA缺乏的临床表型相似。主要表现包括低丙种球蛋白血症、淋巴细胞增殖、自身免疫性血细胞减少、免疫介导的呼吸道、胃肠道、神经和皮肤受累，这些可能很严重且会导致残疾。这项临床试验的基本原理是通过给予CTLA4-Ig（阿巴西普）作为病因性个性化治疗来替代缺乏的CTLA-4，从而改善受影响患者的临床结局。
我们的目的是评估阿巴西普对CTLA-4功能不全或LRBA缺乏患者的安全性和疗效。该研究还将调查阿巴西普治疗如何影响患者的生活质量。
/设计：ABACHAI是一项IIa期前瞻性、非随机、开放标签、单臂多中心试验。总共20名成年患者将接受每周一次皮下注射125 mg阿巴西普治疗，为期12个月，包括（1）已经接受过阿巴西普预处理的患者，以及（2）未接受过预处理的患者，从基线研究访视开始接受阿巴西普治疗。为了评估试验期间的药物安全性感染控制情况，对于疗效，将使用CHAI发病率评分。
该试验已在德国临床试验注册中心（Deutsches Register Klinischer Studien, DRKS）注册，注册号为DRKS00017736，注册时间：2020年7月6日，https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017736 。
