Ceregene, Inc., a biopharmaceutical company, announced that it is progressing with enrolment and dosing in its CERE-120 (AAV2-neurturin) phase II b multi-centre, sham-surgery, double-blinded controlled trial in Parkinson's disease. This trial was initiated in October 2010 and all 11 centres across the United States are now actively enrolling patients.
These sites are among the best movement disorders centres in the country and include Baylor College of Medicine (Houston, Texas), Beth Israel Medical Centre (New York), Columbia University Medical Centre (New York), Duke University School of Medicine (Durham, North Carolina), Emory University Hospital (Atlanta, GA), Mount Sinai Medical Centre (New York), Rush University Medical Centre (Chicago, IL), Stanford University School of Medicine (Palo Alto, CA), University of Alabama (Birmingham, AL), University of California (San Francisco, CA) and University of Pennsylvania Hospital (Philadelphia, PA).
To date, approximately 20 per cent of the 52 subjects have undergone either CERE-120 administration or sham surgery, with many others enrolled and awaiting surgery. It is anticipated that enrollment will be completed near the end of June 2011.
“We appreciate the enthusiasm and support this trial has received from investigators at the study centres as well as from the Parkinson's community. We look forward to completing enrollment as efficiently and responsibly as possible,” stated Jeffrey M. Ostrove, PhD, president and chief executive officer of Ceregene.
This phase II b trial was initiated following the successful dosing of six patients in a phase I safety trial that evaluated, for the first time, the feasibility and safety of targeting the substantia nigra with CERE-120, as well as administering a larger dose than had been tested previously. The phase I safety database currently reflects follow-up periods ranging from seven to 13 months per patient, and shows no Serious Adverse Events (SAEs) in any of the six subjects dosed, including no effect on weight.
All patients were discharged from the hospital within 48 hours of surgery, as planned. Consistent with the safety profile observed in the phase I trial, no CERE-120-related serious adverse events have been observed in the ongoing phase II trial. In total, approximately 60 subjects with Parkinson's disease have now been treated with CERE-120 across four studies (several as long as five years ago) of which approximately 10 received the new dosing paradigm targeting the substantia nigra.
“It is encouraging that CERE-120 continues to appear safe and that the new dosing paradigm we implemented seems well-tolerated,” stated Joao Siffert, MD, Ceregene's vice president, chief medical officer.
The current phase II b trial is designed to test whether CERE-120, when delivered to the degenerating neuronal cell bodies (in the substantia nigra) as well as the terminals of these neurons (in the putamen) can restore sufficient function to produce meaningful clinical benefit. This improved dosing paradigm is based on insight gained from a prior CERE-120 phase II clinical trial in Parkinson's disease patients (Marks et al, Lancet Neurology, 2010; Bartus et al, Movement Disorders, 2010) and is intended to enhance and accelerate the response to CERE-120 previously observed.
“We are pleased and encouraged by our continued progress developing CERE-120 for Parkinson's disease and look forward to eventually determining how much more effective this new dosing paradigm might be for people with Parkinson's disease,” stated Raymond Bartus, PhD, executive vice president and chief scientific officer of Ceregene.
The trial is partially funded through a competitive grant to Ceregene from the Michael J. Fox Foundations' 2010 LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) program on neuro-trophic factors.
CERE-120 is composed of an Adeno-Associated Virus (AAV) vector carrying the gene for neurturin, a naturally occurring protein known to repair damaged and dying dopamine-secreting neurons, keeping them alive and restoring normal function. Neurturin is a member of the same protein family as Glial cell-Derived Neurotrophic Factor (GDNF). The two molecules have similar pharmacological properties, and both have been shown in the laboratory to benefit the midbrain dopamine neurons that degenerate in Parkinson's disease.
Degeneration of these neurons is responsible for the major motor impairments of Parkinson's disease. CERE-120 has been delivered by stereotactic injection to the terminal fields (i.e., the ends of the degenerating neurons), located in an area of the brain called the putamen. The cell bodies for these same neurons are located in a different area of the brain, called the substantia nigra. Once CERE-120 is delivered to the brain, it provides stable, long-lasting expression of neurturin in a highly targeted fashion.
The ongoing phase II b clinical trial of CERE-120 (AAV-neurturin) in patients with Parkinson's disease is actively enrolling subjects at 11 centers across the US. The goal of this clinical trial is to evaluate the safety and potential benefits of CERE-120 in the treatment of Parkinson's disease, employing a new dosing paradigm intended to optimize CERE-120's effect.
Approximately 52 people with Parkinson's disease will participate in this clinical trial. Half of the study subjects will undergo brain surgery to receive CERE-120, while the other half will undergo a similar surgery without receiving any CERE-120 injections (sham or mock surgery). Participants will be carefully monitored by an expert team of study doctors and nurses after the study surgery. Unless their medical condition prohibits it, all patients who initially receive the sham surgery in this trial will be offered CERE-120 when the trial is completed, assuming the data obtained further support the safety and clinical benefit of CERE-120.
Parkinson's disease is a progressive movement disorder that affects a million people in the United States. Its main symptoms, stiffness, tremors and slowed movements and gait, are caused by a loss of dopamine-containing nerve cells in the substantia nigra, which project their axons to the putamen.
Dopamine is a neurotransmitter involved in controlling movement and coordination, so Parkinson's patients exhibit a progressive inability to initiate and control physical movements. There is currently no treatment that can reverse the degeneration of these neurons, let alone cure Parkinson's disease.
The Michael J. Fox Foundation is dedicated to ensuring the development of better treatments, and ultimately a cure, for Parkinson's disease through an aggressively funded research agenda. MJFF has funded $149 million in research to date.
Ceregene, Inc. is a San Diego-based biotechnology company focused on the delivery of nervous system growth (neurotrophic) factors for the treatment of neurodegenerative and retinal disorders using gene delivery.