Clinical Evaluation of NoGo Trap Therapy in Chronic SCI

NoGo Trap 疗法治疗慢性 SCI 的临床评价

• 批准号: 10264886
• 负责人: Erika Smith
• 金额: $ 154.55万
• 依托单位: RENETX BIO, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2023-04-10
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10264886
• 关键词: Activities of Daily Living; Acute; Address; Adult; Antibodies; Binding; Biological; Bolus Infusion; Caring; Cerebrospinal Fluid; Cervical; Cervical spinal cord injury; Chimeric Proteins; Chronic; Classification; Clinical; Clinical Research; Clinical Trials; Data; Development; Direct Costs; Dose; Drug Kinetics; Electrocardiogram; Evaluation; Extracellular Domain; FDA approved; Facilities and Administrative Costs; Family Caregiver; Grant; Hand functions; Human; IgG1; Immunoglobulin G; Impairment; Infusion procedures; Injury; International; Laboratories; Life; Limb structure; Measurement; Measures; Medical; Modeling; Monitor; Monkeys; Motor; Myelin; National Institute of Neurological Disorders and Stroke; Nervous System Physiology; Neurologic; Neurons; Occupational Therapy; Operative Surgical Procedures; Participant; Patient Outcomes Assessments; Patients; Pharmaceutical Preparations; Phase; Phase Ib Clinical Trial; Physical Examination; Physical therapy; Placebo Effect; Placebos; Process; Proteins; Protocols documentation; Randomized; Rattus; Recovery; Recovery of Function; Safety; Sensory; Serum; Spinal Cord; Spinal Cord Contusions; Spinal Puncture; Spinal cord injury; Spinal cord injury patients; Subarachnoid Space; Testing; Therapeutic; Toxicology; United States; United States National Institutes of Health; Upper Extremity; Visit; axon growth; base; central nervous system injury; clinical development; cost; design; disability; double-blind placebo controlled trial; efficacy evaluation; improved; inhibitor/antagonist; neurological recovery; neurorestoration; pre-clinical; preclinical study; primary endpoint; programs; receptor; research clinical testing; secondary endpoint; targeted biomarker; therapeutic candidate; therapy development; virtual

Summary Approximately 300,000 patients suffer from persistent neurological impairment due to chronic spinal cord injury (SCI) in the United States. Currently, there are no FDA-approved drugs to promote neurologic recovery in patients suffering from the life-long, profound impairments due to chronic SCI. An effective neurorestorative therapy would significantly improve the ability of patients to conduct activities of daily living and reduce the burdens for patients, families, and caregivers. Direct and indirect costs associated with care would also be significantly reduced if a successful therapy were developed. The NoGo Trap, a soluble decoy receptor protein comprised of the extracellular domain of NgR1 and IgG Fc, has been shown effective in promoting axon growth and recovery of function in multiple models of CNS injury. These preclinical studies encompassed several different models of SCI including chronic contusion SCI. Recently, the human form of the protein known as AXER-204 has been found to promote corticospinal axon growth and recovery of use of impaired limbs in a monkey model of cervical SCI. IND-enabling development has been completed with NINDS grant support and through NIH’s Bridging Interventional Development Gaps program (BrIDGs) and a Phase 1b clinical trial has been initiated in participants with chronic cervical SCI to determine the safety, tolerability, and pharmacokinetics of single-ascending doses of AXER-204. ReNetX proposes to initiate a repeat-dose Phase 2a clinical trial following completion of the ongoing Phase 1b single-ascending dose study. This repeat-dose, double-blinded, placebo-controlled trial will evaluate the safety, tolerability, and pharmacokinetics of repeat doses of AXER-204. In addition, the trial is designed to evaluate efficacy in promoting recovery of upper limb function. A number of secondary and exploratory endpoints will be evaluated to further assess effects on motor, sensory, and autonomic function. Successful completion of the planned trial will determine if AXER-204 represents a promising therapy for further clinical development as a therapy for chronic SCI. In addition, the data from the trial will help address the paucity of high-quality data in patients with chronic SCI patients and serve to advance SCI clinical research.

总结 大约有30万名患者因慢性脊髓损伤而遭受持续性神经损伤 (SCI)在美国目前，还没有FDA批准的药物可以促进神经系统的恢复。 患者因慢性SCI而终身遭受严重损伤。一种有效的神经修复剂 治疗将显著改善患者进行日常生活活动的能力， 患者、家属和护理人员的负担。与护理相关的直接和间接费用也将 如果开发出成功的治疗方法， NoGo Trap是一种可溶性诱饵受体蛋白，由NgR 1的胞外结构域和IgG Fc组成， 在多种CNS损伤模型中显示出有效促进轴突生长和功能恢复。 这些临床前研究包括几种不同的SCI模型，包括慢性挫伤SCI。 最近，人类形式的蛋白质AXER-204已被发现促进皮质脊髓轴突 脊髓损伤猴模型中受损肢体的生长和使用恢复。有利于IND的发展 在NINDS的资助下，并通过NIH的弥合干预性发展差距项目， 一项1b期临床试验已经在慢性颈脊髓损伤的参与者中启动， 确定单次递增剂量AXER-204的安全性、耐受性和药代动力学。 ReNetX建议在完成正在进行的1b期临床试验后，启动重复给药的2a期临床试验 单次剂量递增研究。这项重复给药、双盲、安慰剂对照试验将评估 AXER-204重复给药的安全性、耐受性和药代动力学。此外，该试验旨在 评价促进上肢功能恢复的疗效。一些次要的和探索性的 将评价终点以进一步评估对运动、感觉和自主神经功能的影响。成功 计划中的试验的完成将决定AXER-204是否代表一种有前途的治疗方法， 作为慢性SCI的治疗方法。此外，试验的数据将有助于解决 高质量的数据，并有助于推动SCI临床研究。