safety and efficacy of cere-120 in subjects with parkinson's disease

Conditions: Idiopathic Parkinson's Disease

Summary: the purpose of this study was to evaluate the safety and potential benefits of cere-120 in the treatment of parkinson's disease.

cere-120 is an experimental drug that consists of an adeno-associated virus (aav) that was engineered to carry the human gene for neurturin, a neurotrophic (growth) factor. similar to other growth factors (such as gdnf), neurturin is capable of restoring function and protecting brain cells from further damage. the virus used in cere-120 is not known to cause disease in people. cere-120 is delivered directly to the brain cells most affected in parkinson's disease - the dopamine producing neurons. cere-120 is injected during brain surgery. once in place, cere-120 continuously produces neurturin. during the first, open-label, part of the study (phase 1), subjects with parkinson's disease received cere-120 at one of two dose levels. in the second part of the study (phase 2), subjects were randomized 1:1 to receive cere-120 or a "sham" surgery where no medication was injected. participants in both phases of the study were followed for up to five years after surgery.

Eligibility criteria:
inclusion criteria: * males and females, ages 35 to 70 years old (inclusive) * a diagnosis of idiopathic parkinson's disease based on uk brain bank criteria, including bradykinesia and at least 1 of the following pd features: resting tremor or rigidity * a hoehn and yahr score of no greater than 3 in the "off" condition at screening * a robust response to dopaminergic therapy as judged by the investigator based on the updrs part iii: motor examination * experiencing motor complications despite adequate antiparkinsonian therapy * a stable, optimized regimen of antiparkinsonian medications and stable parkinsonian features for at least 6 weeks prior to screening * subject is willing not to undergo dbs for at least 12 months after the study surgical procedure (phase 1 subjects) or while the study is blinded (phase 2 subjects) and the investigator believes that this is medically acceptable * medically fit to undergo the study surgical procedure as determined by medical history, clinical and laboratory evaluations, and any other pre-surgical evaluations that are standard at the institution where the subject will undergo surgery * physically and mentally capable of performing all protocol-specified assessments and complying with the study visit schedule * subjects must be able to travel to study visits alone or able to identify a partner or caregiver who agrees to accompany the subject to the study visits * females of childbearing potential must have a negative β-hcg pregnancy test at screening and again before surgery on day 0 * all subjects, both male and female, must agree to practice adequate barrier method contraception for at least 6 months after the surgical procedure * provides written informed consent to participate before any study-specific procedures are conducted exclusion criteria: * atypical or secondary parkinsonism, including, but not limited to, multiple system atrophy (msa) or progressive supranuclear palsy * any subject for whom participation in the study would pose a substantial safety risk * any condition that would compromise the ability of the subject to undergo study procedures, including allergy to gadolinium * presence of any known brain abnormality that could interfere with the assessment of safety or efficacy or represents a surgical risk to the subject * evidence of significant brain atrophy on the baseline mri * history of any cancer other than basal or squamous cell skin cancer within the 3 years prior to screening * any chemotherapy, cytotoxic therapy, or immunotherapy (e.g., il-2, il-12, interferon) within the 3 months prior to screening * any prior treatment for pd with a procedure involving intracranial surgery or implantation of a device (e.g. dbs, pallidotomy) * any prior treatment for a neurological or psychiatric disorders with a procedure involving the implantation of a device (e.g. spinal cord stimulator, vagus nerve stimulator) * history of any prior gene transfer therapy * treatment with any investigational agent within the 3 months prior to screening * anticipated need for antiplatelet agents or anticoagulation therapy, including gingko biloba, during the 10 days prior to the projected surgery date * any vaccinations within the 30 days prior to the projected surgery date note: vaccinations are not allowed for 30 days after the surgical procedure, unless deemed necessary by the investigator for the subject's well-being * not likely to be available for the duration of the trial, likely to be noncompliant with the protocol, or who are deemed unsuitable by the investigator for any other reason * participation in a previous surgical treatment study for parkinson's disease

Keywords: parkinson's disease movement disorders gene therapy neurotrophic factors gdnf neurturin dbs dopamine