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

基本信息

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
项目类别：
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

项目摘要

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）是一种快速进展的神经退行性疾病。有两个 FDA 批准的减缓 ALS 进展的药物：利鲁唑和依达拉奉；他们的效果是鉴于它们针对不同的生物途径，其作用不大，但具有附加性。额外的可以针对病理生理途径提供更多的附加效应。自噬是 ALS 失调，是新疗法开发的一个有希望的目标。海藻糖（SLS-005，Seelos Therapeutics）是一种二糖，以其能力而闻名来激活自噬。三项体内研究证明了 SOD1 小鼠的保护作用型号（G93T 和 G86R）。在人类中，海藻糖酶会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。试验设计包括功效随机对照试验 (RCT)，然后是开放性试验标签扩展 (OLE)。在试验中，参与者每周静脉注射海藻糖，这由训练有素的输液护士在中心或家中完成。不幸的是，海藻糖由于财务原因，大多数参与者的 OLE 将在 RCT 结果公布之前结束由于 Seelos 是一家小型企业，因此受到限制。出于同样的原因，目前还没有扩大访问范围可供不符合 RCT 资格的人使用。当前的提案是海藻糖的扩展获取协议（EAP），其中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，并且不再符合资格参与其他试验（队列 2）。后一组将额外暴露六次几个月。该 EAP 的结果衡量标准将包括安全性、生物流体生物标志物神经丝 light (NFL)、疾病进展和生存的临床测量。这项研究将提供真实的通过评估海藻糖临床开发计划的世界数据该药物在比 RCT 中包含的人群更广泛的人群中的影响收集长期暴露的结果。数据将以以下格式收集：已提交给 FDA，因此可以包含在潜在的 NDA 提交中。