Double-Blind, Multicenter, Sham Surgery Controlled Study of CERE-120 in Subjects With Idiopathic Parkinson's Disease

• ClinicalTrials.gov Identifier: NCT00400634
• Recruitment Status: Completed
• First Posted: November 17, 2006
• Results First Posted: August 14, 2012
• Last Update Posted: November 10, 2022
• Sponsor: Sangamo Therapeutics
• Collaborator: Ceregene
• Information provided by (Responsible Party): Sangamo Therapeutics

Study Description

Brief Summary:

The purpose of this double blind study is to determine whether CERE-120 (adeno-associated virus serotype 2 [AAV2]-neurturin [NTN]) is effective and safe in the treatment of patients with idiopathic Parkinson's Disease. CERE-120 is administered via bilateral stereotactic injections targeting the putaminal region of the brain. The design of this study involves approximately 34 patients receiving CERE-120 treatment via stereotactic surgery and approximately 17 patients receiving sham stereotactic surgery (no CERE-120 administered).

Condition or disease	Intervention/treatment	Phase
Idiopathic Parkinson's Disease	Drug: CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]); Procedure: Sham Surgery	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multicenter, Randomized, Double-Blind, Sham Surgery-Controlled Study of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) to Assess the Efficacy and Safety of Bilateral Intraputaminal (IPu) Delivery in Subjects With Idiopathic Parkinson's Disease
• Study Start Date: November 2006
• Actual Primary Completion Date: November 2008
• Actual Study Completion Date: November 2008

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; Intracerebral administration of CERE-120	Drug: CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]); CERE-120 5.4 x 10^11 vg
Sham Comparator: 2; Sham Neurosurgery	Procedure: Sham Surgery; Bilateral partial thickness burr holes placed, no intraparenchymal injections

Outcome Measures

Primary Outcome Measures :

1. UPDRS Part III OFF [ Time Frame: Change from Baseline to 12 Month Visit ]
   The UPDRS (Unified Parkinson's Disease Rating Scale) is a clinical rating scale that assesses the symptomatic burden of Parkinson's Disease. The scale has four main sections, and each item is scored from a 0 to a 4 (higher number is more severe manifestation). Part III is a subsection devoted to motor function, has 14 questions, resulting in a score range of 0 (unaffected) to 56 (severely affected). The scale is administered by a trained clinician, and patients were assessed in a practically defined "off" condition, 12 hours or more after the last administration of medication.

Other Outcome Measures:

1. UPDRS Part III OFF [ Time Frame: Change from Baseline to 18 Month Visit ]
   The UPDRS (Unified Parkinson's Disease Rating Scale) is a clinical rating scale that assesses the symptomatic burden of Parkinson's Disease. The scale has four main sections, and each item is scored from a 0 to a 4 (higher number is more severe manifestation). Part III is a subsection devoted to motor function, has 14 questions, resulting in a score range of 0 (unaffected) to 56 (severely affected). The scale is administered by a trained clinician, and patients were assessed in a practically defined "off" condition, 12 hours or more after the last administration of medication.

Eligibility Criteria

• Ages Eligible for Study: 35 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Diagnosis of bilateral, idiopathic Parkinson's Disease (PD) based on UK Brain Bank criteria with motor complications despite adequate oral antiparkinsonian therapy.
• At least 5 years disease duration, relative to the anticipated date of surgery, since diagnosis of PD.
• Males or nonpregnant females 35-75 years of age, inclusive.
• A UPDRS motor scale score of 30 or greater in the practically defined off condition during the 30-day eligibility evaluation period.
• Stable doses of antiparkinsonian medications and parkinsonian features for the 60-day period preceding the surgical procedure.
• No conditions that would render the subject unsuitable for surgery, or that would interfere with any of the assessments of efficacy or safety in this trial.
• Subject's informed consent prior to the performance of any study-specific procedures.

Exclusion Criteria:

• Subjects with atypical or secondary parkinsonism.
• Any subject, in the judgment of the investigator, for whom participation in the study would pose a safety risk including, but not limited to, a history of any clinically significant medical, psychiatric, or laboratory abnormality.
• History of treatment of PD by any procedure involving intracranial surgery or implantation of a device.
• MRI of the brain within 12 months before the surgical procedure that indicates the presence of an abnormality that may interfere with the assessments of safety or efficacy or would, in the judgment of the investigator, represent a surgical risk to the subject.
• Any disorder that precludes a surgical procedure (e.g., signs of sepsis or inadequately treated infection) or alters wound healing.
• Receipt of antiplatelet agents for at least 10 days prior to the surgical procedure.
• A score of less than or equal to 27 on the Folstein Mini-Mental examination performed during the eligibility evaluation period or clinical evidence of cognitive impairment that would affect the subject's ability to sign the informed consent or perform any of the protocol required assessments.
• Chemotherapy, cytotoxic therapy, or immunotherapy within 6 weeks prior to the surgical procedure.
• Vaccinations within 30 days prior to the surgical procedure.
• History, within 2 years before the surgical procedure, of drug or alcohol abuse.
• Treatment with neuroleptics within 1 year before the surgical procedure.
• Any medical disability (e.g., severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) that would interfere with the assessment of efficacy and safety in this trial or would compromise the ability of the subject to undergo study procedures (e.g., MRI, PET), or give informed consent.
• History of prior gene transfer therapy.
• Treatment with an investigational agent within 60 days before the surgical procedure.

Contacts and Locations

Locations

United States, Alabama

University of Alabama, Birmingham

Birmingham, Alabama, United States, 35233

United States, California

University of California, San Francisco

San Francisco, California, United States, 94143-0138

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

United States, New York

Mount Sinai School of Medicine

New York, New York, United States, 10029

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27705

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Pennsylvania Hospital

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

Baylor College of Medicine

Houston, Texas, United States, 77030

Sponsors and Collaborators

Sangamo Therapeutics

Ceregene

Investigators

• Study Director: Joao Siffert, M.D.; Ceregene

More Information

Publications of Results:

Marks WJ Jr, Bartus RT, Siffert J, Davis CS, Lozano A, Boulis N, Vitek J, Stacy M, Turner D, Verhagen L, Bakay R, Watts R, Guthrie B, Jankovic J, Simpson R, Tagliati M, Alterman R, Stern M, Baltuch G, Starr PA, Larson PS, Ostrem JL, Nutt J, Kieburtz K, Kordower JH, Olanow CW. Gene delivery of AAV2-neurturin for Parkinson's disease: a double-blind, randomised, controlled trial. Lancet Neurol. 2010 Dec;9(12):1164-1172. doi: 10.1016/S1474-4422(10)70254-4. Epub 2010 Oct 20.

• Responsible Party: Sangamo Therapeutics
• ClinicalTrials.gov Identifier: NCT00400634
• Other Study ID Numbers: CERE-120-02
• First Posted: November 17, 2006
• Results First Posted: August 14, 2012
• Last Update Posted: November 10, 2022
• Last Verified: August 2019

Additional relevant MeSH terms:

Parkinson Disease; Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases