Clinical Evaluation of NoGo Trap Therapy in Chronic SCI

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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.