CLINICAL PROGRAM

The FDA-approved clinical study is a Phase I multi-center trial designed to assess the safety and tolerability of GRNOPC1 in patients with complete ASIA (American Spinal Injury Association) grade A thoracic spinal cord injuries. Spinal cord injuries are graded in severity according to the ASIA grading scale - grade A being the most severe with complete loss of locomotor and sensory activity below the site of the injury. Most such patients do not recover function or respond significantly to physical therapy. The first subjects to receive GRNOPC1 under the clinical protocol will be ASIA grade A injured patients with a thoracic injury resulting in a neurological level of T3 to T10. The therapeutic protocol is also limited to subjects with subacute injuries - injuries that can be treated with GRNOPC1 within seven to 14 days after the injury. Animal studies have demonstrated that GRNOPC1 injections are ineffective if administered more than three months after the injury due to the scarring that occurs in the injured cord as part of the inflammatory response to spinal cord injury.

GRNOPC1 will be injected by qualified, trained spine surgeons seven to 14 days post-injury to patients who give informed consent and also have appropriate laboratory, physical and radiographic characteristics that verify the location and severity of the injury. Because the injection of GRNOPC1 must be precisely controlled, Geron has developed a syringe positioning device that attaches to the frame of the operating room table and enables the spine surgeon to precisely control the needle placement and penetration into the lesion site. All participating spine surgeons will be trained in the use of this device as part of the clinical trial site initiation protocol.

The primary endpoint of the study is safety. Standardized physical examinations and neurological testing will be administered before and after the injection of GRNOPC1 at specified time points for one year after the injection to monitor safety parameters. The secondary endpoint of efficacy will use similar testing for evidence of any return of sensory function or lower extremity motor function for one year after injection of GRNOPC1. Subjects will be immune-suppressed from the time of injection with low-dose tacrolimus for 46 days, at which time the immune suppression will be tapered and withdrawn at 60 days. Subjects will be monitored for a total of 15 years after they are administered GRNOPC1.

Geron has selected up to seven U.S. medical centers as candidates to participate in this study and in planned protocol extensions. The sites are leading referral centers for neurotrauma with experienced, board-certified spine surgeons who will perform the GRNOPC1 injections. Each of the participating medical centers is affiliated with a qualified long-term rehabilitation center where the long-term assessment for safety and efficacy for each treated patient will take place using standard tests administered by trained rehabilitation specialists.

Several additional steps need to be completed prior to initiation of each of the clinical trial sites. These steps include clinical protocol review and approval by the IRB (institutional review board) of each participating medical center. Radiologists and spine surgeons must be trained to ensure uniformity of radiographic interpretation, GRNOPC1 administration and the application of follow-up assessments of safety and efficacy across trial sites. Spine surgeons must be trained to assemble and use the syringe positioning device. All sites need to be instructed and qualified to receive, store and prepare GRNOPC1 from the cryopreserved vials for administration.

After safety is demonstrated in the initial group of subjects, Geron plans to seek FDA approval to extend the study to increase the dose of GRNOPC1, enroll patients with complete cervical injuries, and, ultimately, expand the trial to include patients with severe, incomplete (ASIA grade B or C) injuries to test the safety and utility of GRNOPC1 in as broad a range of severe spinal cord-injured patients as medically appropriate.

Click here to access links for additional spinal cord injury information.