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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Idiopathic Parkinson's Disease

Intervention / Treatment
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* Drug: CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN])
* Procedure: Sham Surgery


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| UPDRS Part III OFF | 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. | Change from Baseline to 12 Month Visit |