Safety and Efficacy of CERE-120 in Subjects With Parkinson's Disease

A Phase 1/2 Trial Assessing the Safety and Efficacy of Bilateral Intraputaminal and Intranigral Administration of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) in Subjects With Idiopathic Parkinson's Disease

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.

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