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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.

肌萎缩侧索硬化症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