~Gained U.S. Department of Defense funding to support a Phase 2 Oxycyte trial

~Established a Clinical Trials Unit

~Organized a working team to assemble an IND (Investigational New Drug) application for a Phase 1 trial of autologous human Schwann cell transplantation

~Had a pre-pre IND discussion with the FDA (Food and Drug Administration) that provided guidance for the design and implementation of FDA-required safety studies to assess the potential risks of Schwann cell transplantation prior to approval for human trial

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CLINICAL TRIALS INITIATIVE

The Human Clinical Trials Initiative is The Miami Project’s efforts to carefully take new discoveries to clinical trial.  The Initiative was announced after Miami Project scientists had encouraging research findings in 2004 that showed up to 70% return of normal walking function in paralyzed laboratory rats.  These results were seen when Schwann cell transplants into the injured spinal cord were combined with injections of an anti-inflammatory drug rolipram and cyclic AMP (a messenger molecule that stimulates nerve fibers to grow).  With this evidence of functional recovery in laboratory animals, The Miami Project has focused on important preclinical activities needed to obtain approval from the Food and Drug Administration (FDA) to begin clinical trials with Schwann cells and rolipram.

The Human Clinical Trials Initiative is also aimed at creating the infrastructure needed to gain approval for and to conduct clinical trials at the University of Miami affiliated hospitals.  The Miami Project is pursuing various preclinical and clinical trial activities that fall under the umbrella of the Initiative.  We anticipate these activities will bring new and potentially life-changing treatments to people with central nervous system trauma.

The Miami Project is currently preparing for, or is involved in, several clinical trials.

These include: 

Autologous

Autologous Schwann Cells for acute and chronic spinal cord injury (preclinical phase):

One of The Miami Project’s most anticipated human clinical trial initiatives is testing human Schwann cell transplants in humans with acute and chronic SCI.  We are preparing our preliminary Investigational New Drug (IND) submission so as to gain approval from the Food and Drug Administration (FDA) to begin a Phase 1 trial. Specifically, we are working on the following preclinical processes:

Communications with the FDA

The Miami Project has secured the services of regulatory consultants at Biologics Consultant Group, Inc. Because of their familiarity with the FDA’s expectations, our consultants provided valuable guidance on the first documents we sent to the FDA to introduce our Schwann cell transplant project plan. They are well qualified to advise us on our project as they are experts in developing cell and tissue-based therapy products and are knowledgeable about the evolving area of regenerative medicine. Because of their advice, we have made significant progress in the preclinical processes necessary to support a successful IND application to the FDA.

 

Human Schwann Cell Manufacturing Process
One required preclinical process relates specifically to how the Schwann cells are prepared for transplantation. To get enough cells, Schwann cells from the trial participant will be used to grow more of their own cells in culture dishes. We must follow Good Manufacturing Process (GMP) when processing the cells to assure the safety and quality of the cells used for transplantation. GMP is a standard recognized internationally that requires documentation of every aspect of the procedures, activities, and operations involved in manufacturing the cells. To become compliant with this standard, we have been working with colleagues at the University of Miami’s Wallace H. Coulter Center for Translational Research, where a GMP laboratory is available. Miami Project staff have spent many hours in this laboratory receiving training from the Coulter Center staff on GMP procedures and establishing Schwann cell manufacturing steps for human cells that will meet the expectations of GMP and the FDA.

 

Human Schwann Cell Safety
Another preclinical process we must complete is a group of studies to test the safety of human Schwann cells. In our previous safety experiments, rat Schwann cells in rats with SCI did not cause tumors, travel to areas away from the transplant site or cause neuropathic pain. To support our IND application, our regulatory consultants have advised that we need to provide evidence to the FDA that our clinical product – the human Schwann cells – are safe. These studies, conducted under conditions similar to GMP studies, will be outsourced to a GLP (Good Laboratory Practice) laboratory and will test whether human Schwann cells produce tumors or cause toxic reactions in rats with acute and chronic SCI. Importantly, these studies will examine transplants of cells that have been processed in exactly the same way we intend to process human Schwann cells for the future clinical trial.

Therapeutic

Therapeutic Hypothermia for acute spinal cord injury and traumatic brain injury
The Miami Project and University of Miami (UM) Department of Neurological Surgery are conducting clinical protocols to learn if inducing hypothermia (cooling) within the first few hours of traumatic spinal cord or brain injury is neuroprotective and makes a difference in the severity of injury.  When a person with a new injury is brought to the trauma center, doctors place a cooling catheter in a large blood vessel (vena cava) that allows them to cool the body a few degrees to 33 degrees Celsius (or 92 degrees Fahrenheit).  The cooling is maintained for a 48 hour period and then the patient is slowly re-warmed at one degree every eight hours.  The researchers are following the participants for at least one year to compare outcomes.

In addition to this single center trial, the neurosurgeons have launched an initiative to study hypothermia treatment for acute traumatic spinal cord injury (SCI) in a multicenter clinical trial. For the hypothermia to become a standard in acute SCI care, a randomized, prospective trial involving multiple centers will be needed to prove that hypothermia is safe and effective. University of Miami neurosurgeons are discussing the possibility of conducting this trial with the Neurological Emergencies Treatment Trials group (NETT).  NETT is a network of 17 academic medical centers with emergency care clinicians available to conduct large multicenter clinical trials.

Cethrin

Cethrin for acute spinal cord injury:
Miami Project neurosurgeon scientists are in negotiations with Alseres Pharmaceuticals, Inc. for the University of Miami to become an investigator site for a Phase 2 multicenter trial of a neuroprotective drug Cethrin.  In preclinical studies, the drug has been shown to block an inhibitory injury mechanism that prevents axons from regrowing. A Phase 1 trial involving 27 patients with acute SCI has already been completed and suggests Cethrin is safe and well-tolerated. The data from this trial also suggests the treatment may improve a participant’s motor and sensory function. When the Phase 2 trial is approved by the FDA, The Miami Project will proceed with the trial once it receives University of Miami Institutional Review Board (IRB) approval.

Oxycyte 
Oxycyte for acute traumatic brain injury: 
At least 5 new clinical trials in traumatic brain injury (TBI) will begin when clinical investigators receive approval from the IRB. One of the trials will test the safety and efficacy of “Oxycyte,” a perfluorocarbon that improves brain oxygenation.  Oxycyte is an oxygen transport enhancer, capable of carrying four times the normal amount of oxygen than a normal human red blood cell. By introducing Oxycyte to the brain or spinal cord after injury, the investigators hope this will increase the oxygen delivered to the injured tissue and reduce the amount of permanent damage to nerve tissue.  The Oxycyte trial is scheduled to begin in the Fall of 2008. 

Other scheduled studies involving people with TBI will measure the levels of neurotoxins in cerebrospinal fluid and plasma.  As neurotoxins are thought to play a major role in TBI, the findings from these studies will help researchers design new drugs to blunt the release of neurotoxins and potentially improve the outcome of patients with TBI.

Riluzole

Riluzole for acute spinal cord injury: 
The Miami Project and UM Department of Neurological Surgery have become a part of the North American Clinical Trials Network (NACTN).  NACTN is a network of institutions that is developing the infrastructure, methods and skilled personnel needed to conduct trials for SCI.  Presently, the collaborative centers are collecting baseline and outcome data from newly injured patients to determine the outcomes and complications that occur in patients receiving the best standard of care. This information will help determine the design of SCI clinical trials. 

NACTN will also conduct a clinical trial of the drug Riluzole.  Riluzole has been approved for patients with amyotrophic lateral sclerosis (ALS).  When Riluzole was tested in preclinical experimental SCI, it had a neuroprotective effect by blocking sodium from entering damaged nerve cells, which may prevent them from swelling and dying.  We expect to begin this Phase 1 trial at The Miami Project/UM once we receive IRB approval.