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

NCT ID: NCT00985517

Last Updated: 2020-04-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-29
• Study Completion Date: 2017-11-16

Brief Summary

The purpose of this study was to evaluate the safety and potential benefits of CERE-120 in the treatment of Parkinson's disease.

Detailed Description

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.

Conditions

Idiopathic Parkinson's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Phase 1: Cohort 1

CERE-120 9.4 x 10\^11 vg, injected by a neurosurgeon directly in the substantia nigra and in the putamen

Group Type: EXPERIMENTAL

CERE-120: Adeno-Associated Virus Delivery of Neurturin

Intervention Type: BIOLOGICAL

Phase 1: Cohort 2

CERE-120 2.4 x 10\^12 vg, injected by a neurosurgeon directly in the substantia nigra and in the putamen

Group Type: EXPERIMENTAL

CERE-120: Adeno-Associated Virus Delivery of Neurturin

Intervention Type: BIOLOGICAL

Phase 2: CERE-120

CERE-120 2.4 x 10\^12 vg, injected by a neurosurgeon directly in the substantia nigra and in the putamen

Group Type: EXPERIMENTAL

CERE-120: Adeno-Associated Virus Delivery of Neurturin

Intervention Type: BIOLOGICAL

Phase 2: Sham Surgery

Neurosurgical procedure that mimics the procedure for CERE-120 delivery. No injections were administered during sham surgery.

Group Type: SHAM_COMPARATOR

Sham Surgery

Intervention Type: PROCEDURE

Interventions

CERE-120: Adeno-Associated Virus Delivery of Neurturin

Intervention Type: BIOLOGICAL

Sham Surgery

Intervention Type: PROCEDURE

Other Intervention Names

AAV2-Neurturin

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

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sangamo Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Stanford School of Medicine

Palo Alto, California, United States

University of California, San Francisco

San Francisco, California, United States

Emory University

Atlanta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Beth Israel Medical Center

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Duke University

Durham, North Carolina, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Countries

United States

References

Bartus RT, Baumann TL, Siffert J, Herzog CD, Alterman R, Boulis N, Turner DA, Stacy M, Lang AE, Lozano AM, Olanow CW. Safety/feasibility of targeting the substantia nigra with AAV2-neurturin in Parkinson patients. Neurology. 2013 Apr 30;80(18):1698-701. doi: 10.1212/WNL.0b013e3182904faa. Epub 2013 Apr 10.

Reference Type: DERIVED

PMID: 23576625 (View on PubMed)

Other Identifiers

CERE-120-09

Identifier Type: -

Identifier Source: org_study_id