An Expanded Access Protocol of Intravenous Trehalose Injection 90 mg/mL Treatment of Patients with Amyotrophic Lateral Sclerosis

静脉注射海藻糖注射液 90 mg/mL 治疗肌萎缩侧索硬化症的扩展方案

• 批准号: 10649756
• 负责人: Suma Babu
• 金额: $ 1813.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-28 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10649756
• 关键词: ALS patients; Amyotrophic Lateral Sclerosis; Autophagocytosis; Biological; Biological Availability; Biological Markers; Businesses; Clinical; Clinical Treatment; Clinical Trials; Control Groups; Data; Data Set; Databases; Disaccharides; Disease Progression; Dose; Double-Blind Method; Eligibility Determination; Enrollment; Equilibrium; Exposure to; FDA approved; Formulation; Goals; Home; Human; Individual; Infusion Nursing; Infusion procedures; Injections; Intravenous; Intravenous infusion procedures; Investigation; Light; Manufacturer Name; Measures; Mediating; Methods; Modeling; Motor; Motor Neurons; Natural History; Nerve Degeneration; Neurons; Oral; Outcome; Outcome Measure; Participant; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phase II/III Trial; Physical Function; Placebo Control; Population; Program Development; Protocols documentation; Quality of life; Questionnaires; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Research; Resources; Respiration; Riluzole; Safety; Serum; Site; Stratification; Testing; Therapeutic; Training; Treatment Protocols; Trehalase; Trehalose; Vital capacity; base; clinical development; clinical effect; clinical efficacy; clinical outcome measures; cohort; design; efficacy clinical trial; efficacy evaluation; improved; in vivo; innovation; mouse model; muscle strength; neurofilament; neuronal survival; new therapeutic target; novel therapeutics; open label; patient population; phase III trial; phenylmethylpyrazolone; preservation; programs; protective effect; standard measure; standard of care; superoxide dismutase 1; therapeutic development; trial design

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative. There are two FDA-approved medications to slow ALS progression, riluzole and edaravone; their effect is modest, but additive given that they target different biological pathways. Additional pathophysiologic pathways can be targeted to provide even more additive effect. Autophagy is dysregulated in ALS and is a promising target for novel therapeutic development. Trehalose (SLS-005, Seelos Therapeutics) is a disaccharide that is well known for its ability to activate autophagy. Three in vivo studies demonstrated a protective effect in SOD1 mouse models (G93T and G86R). In humans, trehalase breaks down trehalose in the gut, so it must be delivered intravenously (IV) to preserve its effect. The safety and efficacy of trehalose are currently being tested in the HEALEY ALS Platform Trial. The trial design includes an efficacy randomized controlled trial (RCT) followed by an open label extension (OLE). In the trial, participants undergo weekly IV infusions of trehalose, which are done either at the center or at home by a trained infusion nurse. Unfortunately, the trehalose OLE will end for most participants before the results of the RCT are known due to financial constraints as Seelos is a small business. For the same reason, expanded access is not currently available to people who are not eligible for the RCT. The current proposal is an expanded access protocol (EAP) of trehalose that will include both people who are not eligible for clinical trials (Cohort 1) as well as people who completed their participation in the trehalose OLE of the HEALEY ALS Platform Trial and are no longer eligible for participation in other trials (Cohort 2). The latter group will be exposed for an additional six months. Outcome measures for this EAP will include safety, the biofluid biomarker neurofilament light (NFL), clinical measures of disease progression, and survival. This study will provide real- world data to supplement the trehalose clinical development program by evaluating the effects of the drug in a population that is broader than the one included in the RCT and by collecting outcomes over longer term exposure. Data will be collected in format that can be submitted to FDA and could therefore be included in a potential NDA submission.

肌萎缩性侧性硬化症（ALS）是一种快速进行性神经退行性。有两个 FDA批准的药物可以减慢ALS进展，riluzole和Edaravone；他们的效果是 谦虚但添加剂鉴于它们针对不同的生物学途径。额外的 可以将病理生理途径靶向以提供更大的添加效应。自噬是 在ALS中失调，是新型治疗发育的有希望的靶标。 海藻糖（SLS-005，Seelos Therapeutics）是一种二糖，以其能力而闻名 激活自噬。三个体内研究表明SOD1小鼠具有保护作用 模型（G93T和G86R）。在人类中，trehalase在肠道中分解了海藻糖，所以必须是 静脉注射（IV）以保持其效果。 海藻糖目前正在Healey ALS平台进行测试 审判。试验设计包括有效性随机对照试验（RCT），然后进行开放 标签扩展（OLE）。在试验中，参与者每周进行海藻糖的静脉输注， 由训练有素的输液护士在中心或家里完成。不幸的是，海藻糖 OLE将在大多数参与者中结束RCT的结果，因为财务已知 作为Seelos的约束是一项小型企业。出于同样的原因，扩展访问当前不是 可用于不符合RCT的人。 当前的建议是海藻糖的扩展访问协议（EAP），其中将包括 两个人都不符合临床试验（队列1）以及完成他们的临床试验的人 参与Healey ALS平台试验的海藻糖油，不再有资格 参加其他试验（队列2）。后一组将额外暴露于六个 月份。 EAP的结果指标将包括安全性，生物流体生物标志物神经丝 光（NFL），疾病进展的临床测量和生存。这项研究将提供真实的 通过评估 该药物在人群中的作用比RCT中包含的药物更广泛 在长期暴露中收集结果。数据将以可能为格式收集 提交给FDA，因此可以包括在潜在的NDA提交中。