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 药代动力学驱动的麦酚酸酯给药的功效和安全性 MoFETIL 用于治疗小儿增殖性狼疮性肾炎 - A 双盲对照临床试验 小儿狼疮性肾炎吗替麦考酚酯 (PLUMM) 研究 项目概要： 成人荟萃分析表明静脉注射环磷酰胺和静脉注射环磷酰胺的临床疗效等效 吗替麦考酚酯根据患者体重或体表面积 (MMFBSA) 给药，目前是这样 美国增殖性狼疮肾炎 (LN) 治疗的标准 MMF（MMKPK）引导精确剂量可能对当前标准治疗提供有益的修改 MMKPK 承诺 LN 响应率比 MMFBSA 高 30% 以上。 充分有力的、随机的、双盲对照的临床试验是为了比较以下药物的有效性和安全性： 药代动力学指导的 MMF 精确给药 (MMFPK) 与 MMF 常规给药方案 (MMFBSA) 在患有增殖性 LN 的儿童中进行的主要假设在这 2 组 104 周中进行检验。 研究表明，与 MMFBSA 相比，MMFPK 导致儿童肾病缓解率显着更高 增殖性 LN 的主要终点是达到至少部分肾功能的受试者比例。 在研究的第 26 周，意向治疗人群的缓解 (PRR) 关键次要终点是。 在研究第 26 周实现完全肾缓解 (CRR) 我们的方法是招募 105 名患者。 年龄 8 岁或以上的儿科受试者，新诊断患有增殖性淋巴结，并且患有 诱导治疗加耐受口服 MMF 的 MMF 随机化将在基线 (1:1) 进行。 第 26 周后，将分别停止 MMKPK 组或 MMFBSA 组的治疗。 积极的研究干预，以及在基线时随机分配至 MMFBSA 组的受试者，这些受试者实现了 PRR 但未达到 CRR 将跨接至 MMFPK 臂，用于测量体积吸收微量采样 (VAMS) 设备。 有助于估计全血中霉酚酸 (MPA) 的暴露量，以满足个性化需求 MMFPK 组中的 MMF 剂量将在试验期间标准化并受到严格监管。 研究，并将监测尿液中的专利生物标志物的遵守情况以提供支持。 试验完成后，我们预计 MMFPK 相对于 MMFBSA 在控制 LN 活性方面​​的优越性。 有明确的证据表明 MMFPK 疗法相比 MMFBSA 使用具有优越性，并表明 MMFPK 剂量耐受性良好，并且在儿童中具有可接受的安全性。 关联： 拟议的试验与公共卫生相关，因为研究了 LN 的治疗方法，即疾病 在这种情况下，优化药物使用有望解决大多数 cSLE 儿童所关心的并发症。 通过快速控制肾脏炎症来改善长期疾病结果，同时最大限度地减少 不必要地接触免疫抑制和致畸药物，这与以下部分有关。 NIH 的使命是促进治疗研究和传播研究信息； LN 的进展是 NIAMS 战略计划及其狼疮研究议程的核心。 改善公共卫生和以患者为中心的个性化护理。