A Phase II, Multicenter, Randomized and Controlled Open-Label Trial Comparing the Safety and Efficacy of Bilateral Intraputaminal (IPu) Administration of CERE-120 (Adeno-Associated Virus Serotype 2 [AAV2]-Neurturin [NTN]) Combined with Best Medical Therapy (BMT) versus BMT-alone in Subjects With Idiopathic Parkinson’s Disease.

• Conditions: idiopathic Parkinson's Disease; MedDRA version: 9.1Level: LLTClassification code 10061536Term: Parkinson's disease

• Registration Number: EUCTR2007-006721-27-GB
• Lead Sponsor: Ceregene Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02-25
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Males and females ages 35 – 75 years old. Females must be either surgically sterile or 2-years post-menopausal and have a negative serum HCG pregnancy test at Screening and Baseline. All patients must agree to practice adequate barrier method contraception for at least six months after CERE-120 administration;
2. Diagnosis of bilateral, idiopathic PD based on UK Brain Bank criteria with motor complications despite adequate antiparkinsonian therapy. This will be based on medical history and neurologic examination (the presence of at least 2 of the following: resting tremor, rigidity, or bradykinesia);
3. At least 5 years disease duration since diagnosis of PD;
4. A robust response to dopaminergic therapy, i.e., approximately a 50% reduction of UPDRS Part III Motor score in the 12-hrs practically defined off” condition when the subject receives an L-Dopa equivalent of their standard morning dose of antiparkinsonian therapy;
5. A Hoehn and Yahr on” score of 3 or less and a score of 1 or 0 on item #30 of the UPDRS Part III: Motor Examination in the on” condition at Screening;
6. Each subject must also have:
• A score of =30 on the UPDRS Part III: Motor Examination in the practically defined off” condition at the Screening Visit;
• A score of = 25 on the UPDRS Part III: Motor Examination in the on” condition at the Screening visit;
7. Stable, optimized (BMT) regimen of antiparkinsonian medications and stable parkinsonian features, for the 3-week period preceding the Baseline Visit;
8. Clinically significant motor fluctuations with an average of at least 2 hours of off” time per day (based on reported history at Screening), despite adequate antiparkinsonian therapy;
9. Subject is willing to not undergo DBS during the course of the study and the investigator believes this is medically acceptable;
10. Subject is willing to not receive treatment with apomorphine IV infusions, routine administration of apomorphine injections or Duodopa® during the course of the study and the investigator believes this is medically acceptable. (Apomorphine injection may given as rescue therapy if the investigator feels this is required);
11. The subject has a score of 130 or greater on the Mattis Dementia Scale at Screening;
12. The subject has no evidence of Major Depression as evidenced by a score of 0-19 on the MADRS at Baseline;
13. Normal coagulation tests and normal platelet levels;
14. The subject is expected to be able to understand and comply with the required visit schedule and all required tests and procedures;
15. The subject is physically and mentally capable of performing the necessary protocol-specified assessments;
16. The subject is medically able to undergo the surgery required to complete the surgical procedure as determined by medical and surgical history, clinical and laboratory evaluations and any other evaluations that are part of the standard practice at the institution in which the subject is to undergo surgery;
17. Signed informed consent is obtained before any study-specific procedure, including assessments required during the Eligibility Evaluation Period.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects with atypical or secondary parkinsonism;
2. Any subject for whom, in the judgment of the principal investigator, participation in the study would pose a safety risk, including but not limited to:
• history of significant drug–induced hallucinations (within the last twelve months from proposed surgical procedure), psychosis, schizophrenia, or any recent major affective disorder;
• treatment with neuroleptics for psychosis, schizophrenia, or any recent major affective disorder within 1 year before the anticipated surgical procedure;
• history, within two years before the anticipated surgical procedure, of drug or alcohol abuse;
• significant cardiovascular risks or history of cardiovascular disorder, unless the subject is cleared after careful medical evaluation;
• any disorder that precludes a surgical procedure or alters wound healing (e.g., signs of sepsis or inadequately treated infection);
• any clinically significant physical or laboratory finding;
• any concomitant serious medical illness that might pose a safety risk;
3. Evidence of significant brain atrophy per Screening MRI;
4. Presence of any known brain 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;
5. Any medical disability (e.g., severe degenerative arthritis, compromised nutritional state, peripheral neuropathy) or any clinical evidence of cognitive impairment that would interfere with the assessment of safety and efficacy in this trial or would compromise the ability of the subject to undergo study procedures (e.g., MRI), or to give informed consent;
6. History of treatment of PD by any procedure involving intracranial surgery or implantation of a device;
7. Receipt of antiplatelet agents or anticoagulation therapy for at least 10 days prior to surgical procedure;
8. Chemotherapy, cytotoxic therapy, or immunotherapy (e.g., IL-2, IL-12, interferon) within 6 weeks prior to the surgical procedure;
9. Vaccinations within 30 days prior to the surgical procedure. (Also no vaccinations within 30 days after their surgical procedure, unless deemed necessary by the investigator for the subject’s safety);
10. History of prior gene transfer therapy;
11. Treatment with an investigational agent within 60 days before the anticipated surgical procedure;
12. Subjects who are not able to travel alone according to their own judgment or to the investigator’s opinion, should be accompanied by a partner or caregiver during traveling to the study visits;
13. Subjects who will be unavailable for the duration of the trial, likely to be noncompliant with the protocol, or who are felt to be unsuitable by the Investigator for any other reason.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the safety and efficacy of bilateral IPu CERE-120 (AAV2-NTN) administration with an optimized and stable regimen of antiparkinsonian medication, Best Medical Therapy” (BMT), in subjects with idiopathic Parkinson's Disease.;Secondary Objective: ;Primary end point(s): To compare the ability of CERE-120 plus BMT versus BMT-only to reduce the severity of motor symptoms as assessed by the change from baseline in the Unified Parkinson’s Disease Rating Scale (UPDRS) part III (Motor Score) in the practically defined off” condition, after 12 months of observation.