权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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：
Suma Babu
金额：
$ 1120.3万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
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：
https://reporter.nih.gov/project-details/10834469
关键词：
Academic Medical Centers Acceleration Address Adverse event Amyotrophic Lateral Sclerosis Anti-Inflammatory Agents Antigens Antiinflammatory Effect Arizona Autologous Berry Biological Blood Component Removal Blood specimen CXCL5 gene Cell Therapy Cells Cellular Assay Cessation of life Characteristics Clinic Clinical Clinical Trials Collaborations Comparison arm Data Science Databases Disease Progression Dose Enrollment Ensure Event FDA approved FOXP3 gene Failure GATA3 gene General Hospitals Geographic Locations Goals Homing Hospitals Hybrids IL16 gene IL8 gene Idaho Immune System Diseases Immunotherapy Inflammasome Inflammation Inflammatory Infusion procedures Interleukin-10 Interleukin-16 Interleukin-4 Interleukin-6 Intervention Intravenous infusion procedures Iowa LOX gene Light Machine Learning Mediating Methods Microglia Morbidity - disease rate Nerve Degeneration Neurodegenerative Disorders Oregon Outcome Oxidative Stress Participant Patients Peripheral Persons Phase Phase II/III Trial Phenotype Placebos Population Prevention Protocols documentation Research Research Personnel Respiratory Failure Riluzole Risk Safety Sampling Serum Signal Transduction Site Symptoms T cell regulation T cell therapy T-Lymphocyte TNF gene Testing Th2 Cells Therapeutic Therapeutic Effect Thymus Gland Time Underserved Population Up-Regulation Vital capacity amyotrophic lateral sclerosis therapy arm cell type chemokine chemotherapy cohort conditioning cytokine design experience high risk high risk population immune checkpoint immune reconstitution improved in vivo manufacture mortality mouse model neurofilament neuroinflammation novel oxidized low density lipoprotein phase I trial phase I/IIa trial phenylmethylpyrazolone prediction algorithm prognostic programmed cell death ligand 1 programmed cell death protein 1 pulmonary function decline remote monitoring safety and feasibility slow potential stem targeted agent treatment effect trend virtual

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。