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.
ALS 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
疗法的益处有限,并且不能解决炎症。为了解决这个问题,RAPA Therapeutics, LLC
(RAPA) 开发了一种可减少炎症的自体 T 细胞疗法 (RAPA-501),目的是
降低 ALS 发病率和死亡率。 RAPA-501 是在体外制造的,以获得双重 TREG/Th2 抗
炎症活动和 T 干表型允许 T 细胞治疗而无需预处理化疗。在
一项正在进行的 RAPA-501 在 ALS 患者 (pwALS) (NCT04220190) 中的临床试验,发现了 RAPA-501 细胞
安全(无与产品相关的不良事件)、生物活性(pwALS 中的多种抗炎作用)、
并显示出稳定肺功能下降的早期趋势。添加了 2/3 期扩展队列
参加评估 RAPA-501 对标准风险 pwALS 是否有效的试验。
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 试验资格的 pwALS,
几乎普遍要求参与者的慢肺活量 (SVC) 值≥预测值的 50%
普通的。拟议的 EAP 将招募 SVC 值 <50% 的 pwALS。 pwALS 的这一群体是
被认为是“高风险”(180 天内呼吸衰竭或死亡的可能性约为 50%),因此特别适合
用于实验性免疫疗法,例如 RAPA-501。此外,RAPA-501-EAP 不会排除 pwALS
长期出现 ALS 相关症状或 ALSFRS-R 评分较低的人。参与者将获得四份
RAPA-501 IV 输注(每 42 天一次,按既定安全剂量,80 x 106 个细胞/输注)。这个 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
行动,并使用标准方法和评估在现实世界的 pwALS 人群中的功效信号
Origent Data Sciences 机器学习 ALS 预测算法。
RAPA-501 EAP 将由麻省总医院 (MGH) 的研究人员领导;Berry 博士、Babu 博士和
Paganoni)并由 RAPA 赞助,RAPA 负责 RAPA-501 的制造和 FDA 监管
根据现有 IND 019480 提交申请(Fowler 博士,发起人)。临床试验现场研究者有以下经验
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
疗法。站点地理分布广泛,可能会积累大量服务不足的 pwALS(U
爱荷华州;爱达荷大学;普罗维登斯医院,俄勒冈州波特兰;加州大学欧文分校;哥伦比亚,纽约)。此外,还有几个
研究合作将源于对临床注释的有价值研究的深入研究
从 RAPA-501 EAP 获得的样品。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ 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:
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