The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) Study

小儿狼疮性肾炎吗替麦考酚酯 (PLUMM) 研究

• 批准号: 10663270
• 负责人: Hermine I Brunner
• 金额: $ 119.6万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10663270
• 关键词: 8 year old; Achievement; Address; Adherence; Adrenal Cortex Hormones; Adult; Award; Biological Assay; Biological Markers; Blood specimen; Body Surface Area; Child; Childhood; Clinical; Clinical Trials; Complex; Consensus; Controlled Clinical Trials; Creatinine; Cyclophosphamide; Data; Development; Devices; Disease; Disease Outcome; Disease remission; Dose; Double-Blind Method; Drug Kinetics; Drug usage; Eligibility Determination; Enrollment; Erythrocytes; Exposure to; Flare; Fostering; Frequencies; Funding; Gender; Glomerular Filtration Rate; Guidelines; Immunosuppressive Agents; Individual; Inflammation; Information Dissemination; Intake; Intention; Intervention Studies; Intravenous; Kidney; Kidney Diseases; Knowledge; Legal patent; Lupus; Lupus Nephritis; Measures; Meta-Analysis; Methodology; Mission; Modification; Monitor; Mycophenolic Acid; National Institute of Arthritis, and Musculoskeletal, and Skin Diseases; Neoadjuvant Therapy; Newly Diagnosed; Onset of illness; Oral; Organ; Outcome; Patients; Pharmaceutical Preparations; Physicians; Population; Positioning Attribute; Prognosis; Proteins; Proteinuria; Public Health; Race; Randomized; Regimen; Research; Research Ethics; Research Personnel; Safety; Sampling; Site; Standardization; Steroids; Strategic Planning; Technology; Teratogens; Testing; Time; United States National Institutes of Health; Urine; Weight; Whole Blood; arm; base; clinical assay development; clinical care; clinical efficacy; clinically relevant; comparative efficacy; conventional dosing; dosage; health related quality of life; home test; improved; meetings; mycophenolate mofetil; nephritis therapy; novel; open label; patient oriented; pediatric lupus; personalized care; primary endpoint; randomized trial; randomized, clinical trials; response; secondary endpoint; smartphone application; standard care; standard of care; trend; trial planning

TITLE EFFICACY & SAFETY OF PHARMACOKINETICALLY-DRIVEN DOSING OF MYCOPHENOLATE MOFETIL FOR THE TREATMENT OF PEDIATRIC PROLIFERATIVE LUPUS NEPHRITIS - A DOUBLE-BLIND CONTROLLED CLINICAL TRIAL The Pediatric Lupus Nephritis Mycophenolate Mofetil (PLUMM) Study PROJECT SUMMARY: Meta-analyses in adults suggest equivalence of clinical efficacy of intravenous cyclophosphamide and mycophenolate mofetil when dosed based on patient weight or body-surface-area (MMFBSA) as is the current standard for the treatment of proliferative lupus nephritis (LN) treatments in the U.S. Pharmacokinetically- guided precision dosing of MMF (MMKPK) may offer a beneficial modification of the current standard treatment in that MMKPK promises over 30% higher LN response rates than MMFBSA. The objective of the proposed, adequately powered, randomized, double-blind controlled clinical trial is to compare the efficacy and safety of pharmacokinetically-guided precision dosing of MMF (MMFPK) with conventional dosing regimens of MMF (MMFBSA) among children with proliferative LN. The principal hypothesis to be tested in this 2-arm 104-week study is that, compared to MMFBSA, MMFPK results in significantly higher rates of renal remission in children with proliferative LN. The primary endpoint is the proportion of subjects achieving at least partial renal remission (PRR) at week 26 of the study in the intention to treat population. The key secondary endpoint is achievement of complete renal remission (CRR) at week 26 of the study. Our approach will be to enroll 105 pediatric subjects, ages 8 years or older, who have been newly diagnosed with proliferative LN plus have chosen MMF for induction therapy plus tolerate oral MMF. Randomization will occur at baseline (1:1) to the MMKPK arm or the MMFBSA arm, respectively. After week 26, non-responders will be discontinued from the active study intervention, and subjects randomized at baseline to the MMFBSA arm who achieved PRR but not CRR will cross over to the MMFPK arm. Volumetric Absorptive Microsampling (VAMS) devices will be used to facilitate estimation of the exposure to mycophenolic acid (MPA) in whole blood as is needed to personalize MMF dosing in the MMFPK arm. Use of corticosteroid will be standardized and closely regulated during the study, and adherence to MMF will be monitored. Patented biomarkers will be assayed in the urine in support of the superiority of MMFPK over MMFBSA in controlling LN activity. Upon completion of this trial, we expect to have unequivocal evidence of the superiority MMFPK therapy compared to MMFBSA use, and to show that MMFPK dosage is well tolerated and has an acceptable safety profile in children. RELEVANCE: The proposed trial is relevant to public health because therapies for LN are investigated, i.e. disease complications that concern the majority of children with cSLE. In this setting, optimizing drug use promises to improve long-term disease outcomes through rapid control of kidney inflammation, while minimzing unnecessary exposures to an immunosuppressive and teratogenic medication. This is relevant to the part of NIH’s mission that pertains to fostering research in treatment; and the dissemination of information on research progress in lupus. LN is central to NIAMS Strategic Plan and its Lupus Research Agenda in pursuance of improved public health and patient-centered personalized care.

标题 霉酚酸盐的药代动力学剂量的功效和安全性 莫菲尔治疗小儿增殖性狼疮肾炎-A 双盲对照临床试验 小儿狼疮肾炎菌根酸酯（Plumm）研究 项目摘要： 成年人中的荟萃分析表明，静脉注射环磷酰胺和 基于患者的体重或身体表面面积（MMFBSA）服用时，霉酚酸酯莫菲蒂（MMFBSA） 在美国药代的药物中治疗增生狼疮肾炎（LN）治疗的标准 MMF（MMKPK）的指导精度剂量可能会对当前标准治疗进行有益的修改 在该MMKPK中，LN响应率比MMFBSA高30％以上。提议的目标， 足够的动力，随机，双盲对照临床试验是为了比较 MMF的MMF（MMFPK）的药代动力学指导精度给药 （MMFBSA）在LN增殖的儿童中。在此2臂104周中要测试的主要假设 研究是，与MMFBSA相比，MMFPK导致儿童的肾脏缓解率明显更高 与增殖的LN。主要终点是获得至少部分肾脏的受试者的比例 该研究第26周的缓解（PRR）是为了治疗人群。关键的次要端点是 在研究第26周实现完全肾脏缓解（CRR）。我们的方法是注册105 8岁或以上的儿科受试者被新诊断为LN Plus的新诊断 选择用于诱导疗法的MMF加上耐受口服MMF。随机化将在基线（1：1）发生到 MMKPK臂或MMFBSA臂。第26周后，非反应者将与 积极的研究干预措施，并在基线时随机与获得PRR但未达到PRR的MMFBSA组 CRR将越过MMFPK臂。体积吸收微采样（VAM）设备将用于 促进估计全血中对全血的暴露于霉酚酸（MPA）的估计 MMF在MMFPK臂中给药。皮质类固醇的使用将被标准化，并在此期间密切调节 研究和遵守MMF将受到监测。获得专利的生物标志物将在尿液中分配 MMFPK优于MMFBSA在控制LN活性方面的优势。审判完成后，我们希望 与使用MMFBSA相比，具有优势MMFPK疗法的明确证据，并证明 MMFPK剂量的耐受性良好，儿童具有可接受的安全性。 关联： 拟议的试验与公共卫生有关，因为研究了LN的疗法，即疾病 与大多数CSLE儿童有关的并发症。在这种情况下，优化药物使用承诺 通过快速控制肾脏感染，改善长期疾病结局，同时最小化 不必要的暴露于免疫抑制和致化药物。这与 NIH的使命与促进治疗研究有关；以及有关研究信息的传播 狼疮的进度。 LN是NIAMS战略计划及其狼疮研究议程的核心 改善了公共卫生和以患者为中心的个性化护理。