New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia.
New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia.
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DOI：
10.1136/bmjopen-2021-052897
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发表时间：
2021-12-31
期刊：
影响因子：
2.9
通讯作者：
Almeida IC
中科院分区：
文献类型：
--
作者：
Alonso-Vega C;Urbina JA;Sanz S;Pinazo MJ;Pinto JJ;Gonzalez VR;Rojas G;Ortiz L;Garcia W;Lozano D;Soy D;Maldonado RA;Nagarkatti R;Debrabant A;Schijman A;Thomas MC;López MC;Michael K;Ribeiro I;Gascon J;Torrico F;Almeida IC
恰加斯病（CD）影响着全世界约700万人。苯并硝唑（BZN）和硝呋替莫（NFX）是唯一被批准用于CD化疗的药物。虽然这两种药物对急性和儿科感染都非常有效，但它们对成人慢性CD （CCD）的疗效较低且不稳定。此外，两种药物的高发生率不良事件（ae）阻碍了它们的广泛使用。在CCD成人中进行的试验表明，在约80%的患者接受标准护理（SoC） BZN治疗后的12个月内，定量PCR （qPCR）检测结果仍为阴性。BZN的药代动力学数据和哺乳动物寄生寄生虫增殖期的非同步性表明，较低的BZN/NFX给药频率，结合标准或延长的治疗时间，可能具有与两种药物SoC相同或更好的疗效，且不良反应更少。南美锥虫感染的新疗法和生物标志物（TESEO）是一项开放标签、随机、前瞻性2期临床试验，共有6个治疗组（75名患者/组，450名患者）。主要目的是比较两种新提出的BZN和NFX化疗方案对成年CCD患者的安全性和有效性，并通过qPCR和生物标志物评估治疗后36个月的BZN和NFX的SoC，并与CD常规血清学相关。患者招募于2019年12月18日和2021年5月20日开始，450名患者（研究目标）被随机分配到六个治疗组中。治疗阶段于2021年8月18日完成。次要目标包括评估两种药物在所有治疗组的人群药代动力学、不良反应发生率和寄生虫基因分型。TESEO研究得到了美国国立卫生研究院（NIH）、美国食品和药物管理局（FDA）、多民族玻利维亚国联邦监管机构和参与机构的伦理委员会的批准。研究结果将通过同行评议的期刊、会议和报告传播给NIH、FDA和参与机构。NCT03981523。
Chagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable. Moreover, the high incidence of adverse events (AEs) with both drugs has hampered their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) assays remain negative for 12 months after standard-of-care (SoC) BZN treatment in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX dosing frequency, combined with standard or extended treatment duration, might have the same or better efficacy than either drug SoC, with fewer AEs. New ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an open-label, randomised, prospective, phase-2 clinical trial, with six treatment arms (75 patients/arm, 450 patients). Primary objectives are to compare the safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and biomarkers for 36 months posttreatment and correlated with CD conventional serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 2021, 450 patients (study goal) were randomised among the six treatment arms. The treatment phase was finalised on 18 August 2021. Secondary objectives include evaluation of population pharmacokinetics of both drugs in all treatment arms, the incidence of AEs, and parasite genotyping. The TESEO study was approved by the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), federal regulatory agency of the Plurinational State of Bolivia and the Ethics Committees of the participating institutions. The results will be disseminated via publications in peer-reviewed journals, conferences and reports to the NIH, FDA and participating institutions. NCT03981523.
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