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是一种致命的神经退行性疾病,由神经炎症加速。目前fda批准
治疗具有适度的益处并且不能解决炎症。为了解决这个问题,RAPA Therapeutics,LLC
(RAPA)开发了一种自体T细胞疗法(RAPA-501),可减少炎症,
降低ALS发病率和死亡率。RAPA-501是离体制造的,以获得双重TREG/Th 2抗-
炎性活性和T干细胞表型,其允许T细胞疗法而无需调节化疗。在
一项正在进行的RAPA-501在ALS患者中的临床试验(NCT 04220190),发现RAPA-501细胞
安全(无产品相关不良事件),生物活性(在药物中具有多种抗炎作用),
并显示出稳定肺功能下降的早期趋势。增加了2/3期扩展队列
该试验旨在评估RAPA-501是否对标准风险患者有效。
我们将把RAPA-501疗法扩展到不符合这项正在进行的2/3期试验或其他ALS试验条件的ALS患者,
这几乎普遍要求参与者的慢肺活量(SVC)值≥预测值的50%
正常拟定的EAP将招募SVC值<50%的患者。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如RAPA-501。此外,RAPA-501-EAP将不排除
患者出现ALS相关症状的时间较长或ALSFRS-R评分较低。参与者将获得四个
RAPA-501 IV输注(每42天一次,以确定的安全剂量,80 x 106个细胞/输注)。此RAPA-501-EAP
将进一步评估这种疗法的安全性,扩大对RAPA-501治疗机制的理解
并使用标准方法评估该真实世界的MATEALS人群中的疗效信号,
Origent Data Sciences机器学习ALS预测算法。
RAPA-501 EAP将由马萨诸塞州总医院(MGH; Berry,Babu和
Paganoni),并由负责RAPA-501生产和FDA监管的RAPA赞助。
在现有IND 019480下提交(Dr. Fowler,申办者)。临床试验中心研究者具有以下经验:
RAPA-501疗法(MGH; Hackensack University Medical Center;和马约诊所亚利桑那州)或其它细胞
治疗研究中心的地理位置各不相同,可能会产生大量服务不足的医疗机构(美国
爱荷华州;爱达荷州;普罗维登斯医院,波特兰,俄勒冈州;加州大学欧文分校;纽约市哥伦比亚)。此外,几个
研究合作将产生于对临床注释的、有价值的研究的深入研究
从RAPA-501 EAP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)
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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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