Clinical trial NCT00985517: Safety and Efficacy of CERE-120 in Subjects With Parkinson's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Idiopathic Parkinson's Disease
Keywords: Parkinson's disease
Movement Disorders
Gene Therapy
Neurotrophic Factors
GDNF
Neurturin
DBS
Dopamine
Lead sponsor: Sangamo Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-09-28
Enrollment: 57
Sex: ALL
Minimum age (years): 35
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: In the first part of the study (Phase 1), 2 escalating dose cohorts received CERE-120.

In the second part of the study (Phase 2), subjects were randomized 1:1 to receive CERE-120 or Sham Surgery.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Participants Who Received CERE-120 Treatment
timeFrame: 5 years
measure: Phase 1 and Phase 2: Change From Baseline in Motor Examination Part III Total Score in the "Off" Condition for the CERE-120 Group as Compared to the Sham Surgery Control Group at the Last Double-blind Assessment.
timeFrame: Baseline, Months 15, 18, 21 and 24
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Palo Alto
country: United States
facility: Stanford School of Medicine
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: New York
country: United States
facility: Beth Israel Medical Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
References:
citation: 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.