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.

肌萎缩侧索硬化症(ALS)是一种进展迅速的神经退行性疾病。有两个 FDA批准的延缓ALS进展的药物利鲁唑和依达拉奉；它们的效果是 温和，但考虑到它们针对不同的生物途径，它具有可加性。其他内容 病理生理途径可以有针对性地提供更多的相加效应。自噬是 在肌萎缩侧索硬化症中调节失调，是新的治疗开发的一个有前途的靶点。 海藻糖(SLS-005，Seelos Treeutics)是一种双糖，以其能力而闻名 来激活自噬。三项体内研究证实了对SOD1小鼠的保护作用 型号(G93T和G86R)。在人类中，海藻糖酶分解肠道中的海藻糖，所以它一定是 静脉注射(IV)以保持其效果。 海藻糖的安全性和有效性目前正在Healey ALS平台上进行测试 审判。试验设计包括一项有效性随机对照试验(RCT)，随后是一项开放试验 标签扩展(OLE)。在试验中，参与者每周都要接受静脉注射海藻糖，这是 在中心或在家中由训练有素的输液护士进行。不幸的是，海藻糖 由于财政原因，大多数参与者将在随机对照试验结果公布之前结束OLE 限制，因为Seelos是一家小企业。出于同样的原因，扩展的访问权限目前不是 适用于没有资格参加随机对照试验的人。 当前的提议是海藻糖的扩展接入协议(EAP)，其将包括 不符合临床试验资格的人(队列1)以及完成临床试验的人 参与Healey ALS平台试验的海藻糖OLE，不再有资格 参加其他试验(队列2)。后一组人将再接受6次治疗。 月份。这种EAP的结果指标将包括安全性，生物流体生物标记物神经丝 LIGH(NFL)，疾病进展和存活率的临床测量。这项研究将提供真实的- 世界数据通过评估海藻糖临床开发计划 该药物在人群中的影响比随机对照试验中所包括的人群更广泛，并通过 收集长期暴露的结果。数据收集的格式可以是 提交给食品和药物管理局，因此可以列入潜在的保密协议文件。