Date: 2016-08-31
Type of information: DSMB assessment
phase: 1-2a
Announcement: DSMB assessment
Company: Asterias Biotherapeutics (USA -CA)
Product: AST-OPC1 (oligodendrocyte progenitor cells)
Action
mechanism: cell therapy. AST-OPC1 are oligodendrocyte progenitor cells derived from human embryonic stem cells. The cells have been shown to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for survival, regrowth and conduction of nerve impulses through axons at the injury site.
Disease: spinal cord injury
Therapeutic area: Rare diseases - Regenerative medicine
Country: USA
Trial
details: The SCiStar study is a Phase 1/2a clinical trial designed to evaluate the safety and efficacy of escalating doses of AST-OPC1 in newly injured patients with sensory and motor complete cervical spinal cord injury (SCI), as well as newly injured patients with sensory incomplete SCI. The trial is testing three sequential escalating doses of AST-OPC1 administered at up to 20 million AST-OPC1 cells in as many as 35 patients with sub-acute, C-5 to C-7, motor complete (AIS-A or AIS-B) cervical SCI. These individuals have essentially lost all movement below their injury site and experience severe paralysis of the upper and lower limbs. AIS-A patients have lost all motor and sensory function below their injury site, while AIS-B patients have lost all motor function but may retain some minimal sensory function below their injury site. AST-OPC1 is being administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging procedures to assess the safety and activity of the product. (NCT02302157) The trial is funded in part by a $14.3 million grant from the California Institute for Regenerative Medicine (CIRM)
Latest
news: * On August 31, 2016, Asterias Biotherapeutics announced that its Data Monitoring Committee (DMC) has reviewed the safety data from the initial cohort of three patients dosed with 2 million cells, and a subsequent five patients in the second cohort dosed with 10 million cells, and has cleared the company to now begin dosing a third cohort of 5-8 complete cervical injury patients (AIS-A patients) with the highest dose of 20 million cells. Concurrently, the study is also proceeding with enrolling the first cohort of 5-8 sensory incomplete cervical spinal cord injury patients (AIS-B patients), each of whom will be administered 10 million cells. * On August 31, 2015, Asterias Biotherapeutics, a biotechnology company focused on the emerging field of regenerative medicine, announced that the third patient was successfully dosed at Chicago-based Rush University Medical Center in a Phase 1/2a clinical trial evaluating activity of escalating doses of AST-OPC1 (oligodendrocyte progenitor cells) in newly injured patients with sensory and motor complete cervical spinal cord injury (SCI). This represents the final patient treated at the initial low-dose (2 million cells) safety cohort. The results of the study continue to support a robust safety profile for AST-OPC1, with no serious adverse events observed in any of the three treated patients to date. The first patient in this cohort was dosed at Shepherd Center in Atlanta and has completed the 2-month post-injection assessment. This patient has progressed from a complete ASIA Impairment Scale (AIS) A injury to an incomplete AIS B injury. The lead neurosurgeon for the study, Dr. Richard Fessler from Rush University Medical Center, performed the AST-OPC1 injections in the second and third patients. Dr. Fessler stated, "The injection procedure went very smoothly for both patients and there were no complications. Both patients recovered quickly from the injection surgery and were able to resume their rehabilitation programs soon afterward." The Company expects to begin enrollment of the second dose cohort following Data Monitoring Committee review of the 30-day post-injection safety data from all three patients. The second cohort will enroll five patients who will receive 10 million AST-OPC1 cells. "The safety data in this first cohort now paves the way for testing the higher doses of AST-OPC1 (10-20 million cells) that we believe correspond most closely to the doses that showed the greatest efficacy in animal studies," commented Dr. Edward Wirth, Chief Medical Officer of Asterias. The open-label, single-arm study is being conducted at three centers currently and will include up to twelve centers in the United States. Enrollment in the trial has already begun to accelerate, with 7 weeks elapsed between dosing the first and second patients, and only 3 weeks between dosing the second and third patients. Upon achievement of initial safety data from the first two cohorts of this study, Asterias plans to seek concurrence from the FDA to increase the robustness of the proof of concept in the Phase 1/2a clinical trial by expanding enrollment from 13 patients to up to 40 patients. The Company believes this change will increase the statistical confidence of the safety and efficacy readouts, reduce the risks of the AST-OPC1 program and position the product for potential accelerated regulatory approvals. Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1. In a previous Phase 1 clinical trial, five patients with neurologically complete, thoracic spinal cord injury were administered two million AST-OPC1 cells at the spinal cord injury site 7-14 days post-injury. The subjects received low levels immunosuppression for the next 60 days. Delivery of AST-OPC1 was successful in all five subjects with no serious adverse events associated with the administration of the cells, with AST-OPC1 itself, or the immunosuppressive regimen. No evidence of rejection of AST-OPC1 was observed in detailed immune response monitoring of all subjects. In four of the five subjects, serial MRI scans indicated that reduced spinal cord cavitation may have occurred. Based on the results of this study, Asterias received approval from FDA to progress testing of AST-OPC1 to subjects with complete cervical injuries, which represents the first targeted population for registration trials. * On March 5, 2015, Asterias Biotherapeutics announced that Atlanta-based Shepherd Center, one of the nation's top rehabilitation hospitals for spinal cord injury and brain injury, has commenced enrollment for the Phase 1/2a clinical trial of AST-OPC1 (oligodendrocyte progenitor cells) in newly injured patients with sensory and motor complete cervical spinal cord injury (SCI). The Phase 1/2a trial follows the successful completion of the Phase 1 trial of AST-OPC1, which met its primary endpoints of safety and feasibility when administered to five patients with neurologically complete, thoracic SCI. Shepherd Center was a site in the Phase 1 study and enrolled two of the five subjects in that study. Asterias intends to initiate enrollment for the Phase 1/2a trial at up to seven additional sites in the coming months. The initiation of this trial is in line with the recently announced initiative to accelerate the current timelines for the AST-OPC1 clinical program by approximately six months. In addition, the company plans to seek FDA concurrence to increase the robustness of the proof of concept in the Phase 1/2a clinical trial by expanding enrollment from 13 patients to up to 40 patients. The company believes these changes will increase the statistical confidence of the safety and efficacy readouts, reduce the risks of the AST-OPC1 program and position the product for potential accelerated regulatory approvals. Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.
The results of the ongoing trial continue to support a positive safety profile for AST-OPC1. There have been no serious or unexpected adverse events related to AST-OPC1, the administration procedure or the accompanying short course of low-dose immunosuppression in any of the patients treated with AST-OPC1, including five patients in an earlier Phase 1 trial with neurologically complete thoracic SCI.
The data set evaluating the efficacy results six months after implantation of 10 million AST-OPC1 cells in complete cervical spinal cord injury patients will be available in January 2017 and will focus on improvement in physical functioning of the upper extremities (fingers, hands and arms) of each treated patient utilizing scoring on the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI scale). The published literature and opinion leaders in the spinal cord injury field indicate that a two motor level improvement in functioning utilizing this validated scale is clinically meaningful for these patients and should be the key measure in the evaluation of new therapies.
