Maltby Vicki E, Lea Rodney A, Monif Mastura, Fabis-Pedrini Marzena J, Buzzard Katherine, Kalincik Tomas, Kermode Allan G, Taylor Bruce, Hodgkinson Suzanne, McCombe Pamela, Butzkueven Helmut, Barnett Michael, Lechner-Scott Jeannette
Department of Neurology, John Hunter Hospital, New Lambton Heights, Australia.
School for Medicine and Public Health, University of Newcastle, Callaghan, Australia.
JMIR Res Protoc. 2021 Oct 19;10(10):e24969. doi: 10.2196/24969.
Cladribine tablets (marketed as Mavenclad) are a new oral therapy, which has recently been listed on the pharmaceutical benefits scheme in Australia for the treatment of relapsing multiple sclerosis (MS). The current dosing schedule is for 2 courses given a year apart, which has been shown to be effective for treatment of MS for up to 4 years in 75% of patients (based on annualized relapse rate). However, the reinitiation of therapy after year 4 has not been studied.
This study aims to evaluate the safety and efficacy of cladribine tablets over a 6-year period, according to no evidence of disease activity 3.
This will be a multicenter, 6-year, phase IV, low interventional, observational study that incorporates clinical, hematological, biochemical, epigenetic, radiological and cognitive biomarkers of disease. Participants considered for treatment with cladribine as part of their routine clinical care will be consented to take part in the study. They will be monitored at regular intervals during the initial course of medication administration in years 1 and 2. After year 3, patients will have the option of redosing, if clinically indicated, or to switch to another disease-modifying therapy. Throughout the duration of the study, we will assess blood-based biomarkers including lymphocyte subsets, serum neurofilament light chain, DNA methylation, and RNA analysis as well as magnetic resonance imaging findings (brain volume and/or lesion load) and cognitive performance.
This study has been approved by the Hunter New England Local Health District Human Research Ethics Committee. Recruitment began in March of 2019 and was completed by June 2021.
This will be the first long-term efficacy trial of cladribine, which offers reinitiation of therapy in the 3rd year, based on disease activity, after the initial 2 courses. We expect that this study will indicate whether any of the assessed biomarkers can be used to predict treatment efficacy or the need for future reinitiation of cladribine in people with MS.
This study is registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12619000257167) with Universal Trial Number (U1111-1228-2165).
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24969.
克拉屈滨片（商品名为Mavenclad）是一种新型口服疗法，最近已被列入澳大利亚药品福利计划，用于治疗复发型多发性硬化症（MS）。目前的给药方案是每年间隔给予2个疗程，已证明在75%的患者中（基于年化复发率）该方案对MS治疗长达4年有效。然而，4年后重新开始治疗尚未得到研究。
本研究旨在根据无疾病活动证据3评估克拉屈滨片在6年期间的安全性和有效性。
这将是一项多中心、为期6年的IV期、低干预性观察性研究，纳入疾病的临床、血液学、生化、表观遗传学、放射学和认知生物标志物。考虑将克拉屈滨作为其常规临床护理一部分进行治疗的参与者将被同意参加研究。在第1年和第2年药物给药的初始疗程期间，他们将定期接受监测。3年后，如果有临床指征，患者可以选择重新给药，或改用另一种疾病修饰疗法。在研究期间，我们将评估基于血液的生物标志物，包括淋巴细胞亚群、血清神经丝轻链、DNA甲基化和RNA分析，以及磁共振成像结果（脑容量和/或病灶负荷）和认知表现。
本研究已获得亨特新英格兰地方卫生区人类研究伦理委员会的批准。招募工作于2019年3月开始，并于2021年6月完成。
这将是克拉屈滨的首个长期疗效试验，该试验在初始2个疗程后，根据疾病活动情况，在第3年提供重新开始治疗的机会。我们预计这项研究将表明是否可以使用任何评估的生物标志物来预测治疗效果或MS患者未来重新开始使用克拉屈滨的必要性。
本研究已在澳大利亚和新西兰临床试验注册中心（ACTRN12619000257167）注册，通用试验编号为（U1111-1228-2165）。
国际注册报告识别码（IRRID）：DERR1-10.2196/24969。
