Intermediate-Size Expanded Access Trial of Autologous Hybrid TREG/Th2 Cell Therapy (RAPA-501) of Amyotrophic Lateral Sclerosis
肌萎缩侧索硬化症自体杂交 TREG/Th2 细胞疗法 (RAPA-501) 的中型扩大试验
基本信息
- 批准号:10834469
- 负责人:
- 金额:$ 1120.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-09-25 至 2026-08-31
- 项目状态:未结题
- 来源:
- 关键词:Academic Medical CentersAccelerationAddressAdverse eventAmyotrophic Lateral SclerosisAnti-Inflammatory AgentsAntigensAntiinflammatory EffectArizonaAutologousBerryBiologicalBlood Component RemovalBlood specimenCXCL5 geneCell TherapyCellsCellular AssayCessation of lifeCharacteristicsClinicClinicalClinical TrialsCollaborationsComparison armData ScienceDatabasesDisease ProgressionDoseEnrollmentEnsureEventFDA approvedFOXP3 geneFailureGATA3 geneGeneral HospitalsGeographic LocationsGoalsHomingHospitalsHybridsIL16 geneIL8 geneIdahoImmune System DiseasesImmunotherapyInflammasomeInflammationInflammatoryInfusion proceduresInterleukin-10Interleukin-16Interleukin-4Interleukin-6InterventionIntravenous infusion proceduresIowaLOX geneLightMachine LearningMediatingMethodsMicrogliaMorbidity - disease rateNerve DegenerationNeurodegenerative DisordersOregonOutcomeOxidative StressParticipantPatientsPeripheralPersonsPhasePhase II/III TrialPhenotypePlacebosPopulationPreventionProtocols documentationResearchResearch PersonnelRespiratory FailureRiluzoleRiskSafetySamplingSerumSignal TransductionSiteSymptomsT cell regulationT cell therapyT-LymphocyteTNF geneTestingTh2 CellsTherapeuticTherapeutic EffectThymus GlandTimeUnderserved PopulationUp-RegulationVital capacityamyotrophic lateral sclerosis therapyarmcell typechemokinechemotherapycohortconditioningcytokinedesignexperiencehigh riskhigh risk populationimmune checkpointimmune reconstitutionimprovedin vivomanufacturemortalitymouse modelneurofilamentneuroinflammationnoveloxidized low density lipoproteinphase I trialphase I/IIa trialphenylmethylpyrazoloneprediction algorithmprognosticprogrammed cell death ligand 1programmed cell death protein 1pulmonary function declineremote monitoringsafety and feasibilityslow potentialstemtargeted agenttreatment effecttrendvirtual
项目摘要
ALS is a lethal neurodegenerative disease accelerated by neuroinflammation. Current FDA-approved
therapies have modest benefits and do not address inflammation. To address this, RAPA Therapeutics, LLC
(RAPA) has developed an autologous T cell therapy (RAPA-501) that reduces inflammation, with the goal of
reducing ALS morbidity and mortality. RAPA-501 are manufactured ex vivo to attain dual TREG/Th2 anti-
inflammatory activity and a T-stem phenotype that permits T cell therapy without conditioning chemotherapy. In
an ongoing clinical trial of RAPA-501 in people with ALS (pwALS) (NCT04220190), RAPA-501 cells were found
to be safe (no product-related adverse events), biologically active (diverse anti-inflammatory effects in pwALS),
and showed early trends toward stabilizing pulmonary function decline. A phase 2/3 expansion cohort was added
to the trial to assess whether RAPA-501 is efficacious in standard-risk pwALS.
We will extend RAPA-501 therapy to pwALS not eligible for this ongoing phase 2/3 trial or other ALS trials,
which nearly universally require that participants have a slow vital capacity (SVC) value of ≥50% of predicted
normal. The proposed EAP will enroll pwALS who have SVC values <50%. This population of pwALS is
considered “high risk” (~50% chance of respiratory failure or death within 180 days) and thus particularly suitable
for experimental immune therapies such as RAPA-501. In addition, the RAPA-501-EAP will not exclude pwALS
who have a prolonged time from ALS-related symptoms or low ALSFRS-R scores. Participants will receive four
RAPA-501 IV infusions (every 42-days at established safe dose, 80 x 106 cells/infusion). This RAPA-501-EAP
will further evaluate the safety of this therapy, expand an understanding of the RAPA-501 therapeutic mechanism
of action, and evaluate signals of efficacy in this real-world population of pwALS using standard methods and
Origent Data Sciences machine learning ALS prediction algorithms.
The RAPA-501 EAP will be led by investigators at Mass General Hospital (MGH; Drs. Berry, Babu, and
Paganoni) and sponsored by RAPA, which is responsible for RAPA-501 manufacturing and FDA regulatory
filings under existing IND 019480 (Dr. Fowler, Sponsor). Clinical trial site investigators have experience with
RAPA-501 therapy (MGH; Hackensack University Medical Center; and Mayo Clinic Arizona) or other cells
therapies. Sites are geographically diverse and likely to accrue a significant number of underserved pwALS (U
of Iowa; U of Idaho; Providence Hospital, Portland, Oregon; UC-Irvine; Columbia, NYC). In addition, several
research collaborations will emanate from the intensive study of the clinically-annotated, valuable research
samples obtained from the RAPA-501 EAP.
肌萎缩侧索硬化症是一种由神经炎症加速的致命性神经退行性疾病。目前FDA批准的
疗法的益处不大,而且不能解决炎症问题。为了解决这个问题,Rapa Treeutics,LLC
(RAPA)已经开发出一种自体T细胞疗法(RAPA-501),可以减少炎症,目标是
减少肌萎缩侧索硬化的发病率和死亡率。体外制造RAPA-501以获得双重Treg/Th2抗
炎症活性和T干细胞表型,允许T细胞治疗而不需要条件化疗。在……里面
一项正在进行的RAPA-501在ALS(PwALS)患者(NCT04220190)的临床试验中发现,RAPA-501细胞
安全(没有产品相关的不良事件),生物活性(pwALS的多种抗炎作用),
并显示出稳定肺功能下降的早期趋势。添加了2/3阶段扩展队列
以评估RAPA-501在标准风险pwALS中是否有效。
我们将把RAPA-501疗法扩展到不符合正在进行的2/3期试验或其他ALS试验的pwALS,
这几乎普遍要求参与者的慢肺活量(SVC)值为预测的≥的50%
很正常。拟议的EAP将招收SVC值为50%的pwALS。这群pwal是
被认为是“高风险”(约50%的几率在180天内发生呼吸衰竭或死亡),因此特别适合
用于实验性免疫疗法,如RAPA-501。此外,RAPA-501-EAP将不排除pwALS
ALS相关症状持续时间较长或ALSFRS-R得分较低的患者。参赛者将获得四个
RAPA-501静脉输注(以确定的安全剂量,每42天一次,80×106细胞/输液)。本RAPA-501-EAP
将进一步评估该疗法的安全性,扩大对RAPA-501治疗机制的了解
并使用标准方法和方法评估pwALS这一真实人群中的疗效信号
Origent Data Science机器学习ALS预测算法。
RAPA-501 EAP将由马萨诸塞州综合医院(MGH;Dr.Berry,Babu和
Paganoni),由负责RAPA-501制造和FDA监管的RAPA赞助
根据现有IND 019480标准提交的文件(保荐人福勒博士)。临床试验现场调查人员有经验
RAPA-501疗法(MGH、哈肯萨克大学医学中心和亚利桑那州梅奥诊所)或其他细胞
治疗。地点的地理位置不同,可能会产生大量服务不足的pwALS(U
爱荷华州大学;爱达荷州大学;俄勒冈州波特兰普罗维登斯医院;加州大学欧文分校;哥伦比亚大学,纽约市)。此外,还有几个
研究合作将源于对临床注释的、有价值的研究的密集研究
从RAPA-501EAP获得的样本。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Suma Babu其他文献
Suma Babu的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Suma Babu', 18)}}的其他基金
An Intermediate-Size Expanded Access Protocol for Amyotrophic Lateral Sclerosis with Pridopidine
使用普利多匹定治疗肌萎缩侧索硬化症的中型扩展治疗方案
- 批准号:
10835282 - 财政年份:2023
- 资助金额:
$ 1120.3万 - 项目类别:
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 - 财政年份:2022
- 资助金额:
$ 1120.3万 - 项目类别:
相似海外基金
EXCESS: The role of excess topography and peak ground acceleration on earthquake-preconditioning of landslides
过量:过量地形和峰值地面加速度对滑坡地震预处理的作用
- 批准号:
NE/Y000080/1 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Research Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328975 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Continuing Grant
SHINE: Origin and Evolution of Compressible Fluctuations in the Solar Wind and Their Role in Solar Wind Heating and Acceleration
SHINE:太阳风可压缩脉动的起源和演化及其在太阳风加热和加速中的作用
- 批准号:
2400967 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Standard Grant
Market Entry Acceleration of the Murb Wind Turbine into Remote Telecoms Power
默布风力涡轮机加速进入远程电信电力市场
- 批准号:
10112700 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Collaborative R&D
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328973 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Continuing Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328972 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Continuing Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332916 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Standard Grant
Collaborative Research: A new understanding of droplet breakup: hydrodynamic instability under complex acceleration
合作研究:对液滴破碎的新认识:复杂加速下的流体动力学不稳定性
- 批准号:
2332917 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Standard Grant
Collaborative Research: FuSe: R3AP: Retunable, Reconfigurable, Racetrack-Memory Acceleration Platform
合作研究:FuSe:R3AP:可重调、可重新配置、赛道内存加速平台
- 批准号:
2328974 - 财政年份:2024
- 资助金额:
$ 1120.3万 - 项目类别:
Continuing Grant
Study of the Particle Acceleration and Transport in PWN through X-ray Spectro-polarimetry and GeV Gamma-ray Observtions
通过 X 射线光谱偏振法和 GeV 伽马射线观测研究 PWN 中的粒子加速和输运
- 批准号:
23H01186 - 财政年份:2023
- 资助金额:
$ 1120.3万 - 项目类别:
Grant-in-Aid for Scientific Research (B)














{{item.name}}会员




