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

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 FDA批准的减缓ALS进展的药物，利鲁唑和依达拉奉;它们的效果是 适度，但鉴于它们针对不同的生物途径，它们是相加的。额外 可以靶向病理生理途径以提供甚至更多的累加效应。自噬是 在ALS中的调节异常，并且是新的治疗开发的有希望的靶标。 海藻糖（SLS-005，Seelos Therapeutics）是一种二糖，众所周知其能够 来激活自噬三项体内研究证明了在SOD 1小鼠中的保护作用 型号（G93 T和G86 R）。在人类中，海藻糖酶分解肠道中的海藻糖，所以它必须 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平台中进行测试 审判试验设计包括一项疗效随机对照试验（RCT），随后是一项开放性试验。 标签扩展（OLE）。在试验中，参与者每周静脉输注海藻糖， 都是由经过培训的输液护士在中心或家中完成的。不幸的是海藻糖 由于财务原因，OLE将在RCT结果公布之前结束。 因为Seelos是一家小企业。出于同样的原因，目前还没有扩大的准入。 提供给那些没有资格参加RCT的人。 目前的建议是一个扩大访问协议（EAP）的海藻糖，将包括 没有资格参加临床试验的人（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，不再符合资格 参与其他试验（队列2）。后一组将被暴露在额外的六个 个月本EAP的结局指标将包括安全性、生物流体生物标志物神经丝 光（NFL）、疾病进展的临床测量和存活。这项研究将提供真实的- 通过评价海藻糖临床开发项目的全球数据， 药物在比RCT中纳入的人群更广泛的人群中的作用， 收集长期暴露的结果。数据将以可被 提交给FDA，因此可纳入潜在的NDA提交中。

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.