CLINICAL TRIAL: RHASM IN ADULTS WITH ACID SPHINGOMYELINASE DEFICIENCY (ASMD)

临床试验：患有酸性鞘磷脂酶缺乏症 (ASMD) 的成人中的 RHASM

• 批准号: 7953691
• 负责人: MARGARET M MCGOVERN
• 金额: $ 4.09万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953691
• 关键词: Adrenal hormone preparation; Adult; Adverse event; Aftercare; Age; Aldosterone; Androstenedione; Chemistry; Clinical; Clinical Research; Clinical Trials; Coagulation Process; Computer Retrieval of Information on Scientific Projects Database; Corticotropin; Dose; Drug Kinetics; Echocardiography; Electrocardiogram; Enrollment; Evaluation; Fasting; Funding; Grant; Heart Rate; Hematology; Human; Hydrocortisone; Infusion procedures; Institution; Laboratories; Lipids; Liver; Liver Function Tests; Magnetic Resonance Imaging; Monitor; Niemann-Pick Diseases; Patients; Pharmacodynamics; Phase; Physical Examination; Pulmonary function tests; Recombinants; Reporting; Research; Research Personnel; Resources; Safety; Serum; Severity of illness; Source; Spleen; Splenomegaly; Telephone; Testing; Thoracic Radiography; Time; United States National Institutes of Health; Urinalysis; Visit; acid sphingomyelinase; base; cytokine; follow up assessment; follow-up; immunogenicity; liver biopsy

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase 1, single-center, single-dose, dose escalation study to evaluate the safety, pharmacokinetics and pharmacodynamics of recombinant human acid sphingomyelinase (rhASM) in adults with Niemann Pick disease (NPD) due to ASM deficiency. For each patient, study participation will consist of a screening/baseline evaluation and enrollment phase; a 72-hr in-patient stay during which a single-dose infusion of rhASM will be administered; and a 2842-day post-treatment assessment phase with follow-up assessments at 14 and 28 days post-infusion and a 42-day follow-up phone call. A minimum of 15 eligible adult (age 18 to 65 years, inclusive) patients will be enrolled into the study. Patients will be stratified by the degree of splenomegaly in multiples of normal (MN), as an indicator of disease severity. Five ascending single-dose groups, consisting of a minimum of 3 patients each, will be evaluated for safety, PK and PD. The single doses of rhASM selected for this study are 0.03, 0.1 0.3, 0.6 and 1.0 mg/kg. Dose escalation will proceed sequentially from lowest to highest dose. All patients will be monitored on an in-patient basis for 72 hr following the infusion of rhASM, return for assessments on Days 14 and 28 and receive a follow-up phone call on Day 42. Safety monitoring over the 72-hr in-patient visit will include: adverse event (AE) reporting, physical examinations, vital signs (including continuous monitoring of heart rate), clinical laboratory evaluations (serum chemistries, hematology, coagulation studies, urinalysis), liver function tests (LFTs), and cytokines. In addition, pulmonary function testing (PFT), adrenal hormone levels (diurnal and post-adrenocorticotropic hormone (ACTH) stimulation testing for aldosterone, cortisol, and delta-4-androstenedione levels), fasting lipid profile (FLP), immunogenicity testing, chest X-Rays, electrocardiograms (ECG), echocardiograms (ECHO), liver biopsies, and magnetic resonance imaging (MRI) of the spleen and liver will be performed at selected time points pre- and post-infusion. Hypothesis: Ascending doses of rhASM administered as a single dose to adults with ASMD will be tolerated.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 这是一项单中心、单剂量、剂量递增的 1 期研究，旨在评估重组人酸性鞘磷脂酶 (rhASM) 在因 ASM 缺乏而患有尼曼皮克病 (NPD) 的成人患者中的安全性、药代动力学和药效学。 对于每位患者，研究参与将包括筛选/基线评估和登记阶段；住院 72 小时，期间将进行单剂量 rhASM 输注； 2842 天的治疗后评估阶段，包括输注后 14 天和 28 天的后续评估以及 42 天的电话随访。 至少 15 名符合条件的成人（18 岁至 65 岁，含）患者将被纳入该研究。 将根据正常脾脏肿大程度 (MN) 的倍数对患者进行分层，作为疾病严重程度的指标。 将评估五个升序单剂量组（每个组至少由 3 名患者组成）​​的安全性、PK 和 PD。 本研究选择的rhASM单剂量为0.03、0.1、0.3、0.6和1.0 mg/kg。 剂量递增将从最低剂量到最高剂量依次进行。 所有患者在输注 rhASM 后将接受 72 小时的住院监测，在第 14 天和第 28 天返回进行评估，并在第 42 天接到后续电话。 72 小时住院期间的安全监测访问将包括：不良事件 (AE) 报告、体检、生命体征（包括持续监测心率）、临床实验室评估（血清化学、血液学、凝血研究、尿液分析）、肝功能测试（LFT）和细胞因子。 此外，肺功能测试 (PFT)、肾上腺激素水平（醛固酮、皮质醇和 δ-4-雄烯二酮水平的每日和促肾上腺皮质激素 (ACTH) 刺激测试）、空腹血脂谱 (FLP)、免疫原性测试、胸部检查X 射线、心电图 (ECG)、超声心动图 (ECHO)、肝活检和磁共振成像 (MRI)将在输注前和输注后的选定时间点进行脾脏和肝脏检查。 假设：患有 ASMD 的成人单次服用递增剂量的 rhASM 是可以耐受的。