A Study of AAV-hAADC-2 in Subjects With Parkinson's Disease

NCT00229736 | Completed Phase 1 DMC

• 1 other identifier: AAVhAADC2003
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Safety Study in subjects with Parkinson's Disease

Conditions

Parkinson's Disease

Outcome Measures

Primary Outcomes (1)

• The safety and tolerability of intrastriatal administration of AAV-hAADC-2 as measured by Adverse Events in subjects with mid- to late-stage Parkinson's Disease.

  Time of treatment through Month 60.

Secondary Outcomes (2)

• The effect of AAV-hAADC-2 on clinical status as recorded in subject diaries, by clinical assessment, and daily levodopa requirement.

  Time of treatment through Month 60.

• The relationship between the dose of AAV-hAADC-2 vector infused and the resulting level of striatal AADC expression by FMT-PET imaging.

  Time of treatment through Month 60

Study Arms (2)

AAV-hAADC-2 (9x10^10 vector genomes)

EXPERIMENTAL

Genetic: AAV-hAADC-2

AAV-hAADC-2 (3x10^11 vector genomes)

EXPERIMENTAL

Genetic: AAV-hAADC-2

Interventions

AAV-hAADC-2 GENETIC

9 x 10\^10 vector genomes (vg) of AAV-hAADC-2 in a single dose of 200 µL bilaterally infused over 4 striatal targets

AAV-hAADC-2 (9x10^10 vector genomes)

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent.
• Diagnosis of idiopathic Parkinson's disease (two of four cardinal features - tremor, bradykinesia, rigidity and postural instability - plus early dopaminergic responsiveness of symptoms and absence of any cardinal signs of more widespread neurological disease).
• Age ≤ 75 years.
• Age at diagnosis ≥ 40 years.
• Duration of levodopa therapy ≥ 5 years (number of years is cumulative since diagnosis, does not need to be continuous).
• Hoehn and Yahr Stage III to IV off medication at entry.
• Unified Parkinson's Disease Rating Scale (UPDRS), Part III, minimum motor score of 20 to a maximum motor score of 60 in the "OFF" state.
• Positive response to dopaminergic therapy as evidenced by a decrease in UPDRS motor scores between the defined "OFF" and "ON" states: a minimum of 8 points improvement in the UPDRS after dopaminergic therapy.
• Candidate for surgical therapy for Parkinson's disease because of intractable motor fluctuations, defined as a subscore on UPDRS Part IV section B ("Clinical Fluctuations" score of 3 (minimum) to 7 (maximum) during the "ON" state, not responsive to optimal medical therapy.
• MRI (magnetic resonance imaging)within the past two years and MRI does not show any conditions that are clinically significant with respect to risks for brain surgery.
• Subjects must agree to use barrier contraception, until three consecutive PCR (polymerase chain reaction) samples are negative, if the subject or partner is of childbearing potential.
• Must be able to comply with the requirements of the study, including the need for frequent and prolonged follow-up.
• Subjects must have been on both optimal and stable medications for treatment of their Parkinson's disease for at least two months prior to being eligible for participation in the study.
• Subjects must have baseline Hematology and Chemistry values within the normal laboratory ranges unless the out of range values are not clinically significant with respect to general surgery.

You may not qualify if:

• Unable or unwilling to meet requirements of the study.
• Atypical Parkinsonian syndromes due to drugs (e.g. metoclopramide, flunarizine), metabolic disorders (e.g. Wilson's disease), encephalitis, or degenerative diseases (e.g., juvenile Huntington's disease, progressive supranuclear palsy, multisystem atrophy, dementia with Lewy bodies).
• History of three (3) hours or more of intense or violent dyskinesias in the past six (6) months.
• Previous stereotactic neurosurgery for Parkinson's disease (pallidotomy, thalamotomy, deep brain stimulation).
• Mini-Mental™ State Examination (MMSE) \< 26 or screening neuropsychological evaluation compatible with dementia.
• Hallucinations or delusions due to medication or underlying mental illness within 6 months of screening; documented history of schizophrenia or other psychotic disorder.
• History of serious mood disorder that, in the opinion of the Investigator, is not effectively managed.
• History of stroke or other currently significant or poorly controlled cardiovascular disease.
• Intracranial neoplasia, clinically significant neurological diseases (for example, significant brain atrophy not consistent with age).
• History of other malignancy, with the exception of treated cutaneous squamous cell or basal cell carcinoma, within 5 years.
• Uncontrolled hypertension: systolic blood pressure consistently \>160 mmHg with no attempt at treatment.
• Coagulopathy or need for ongoing anticoagulant therapy.
• Clinically significant immune dysfunction (for example, those that require the use of immunosuppressive drugs).
• Geriatric Depression Scale (GDS; Mood Assessment Scale - Short Form) score of \>10 or, if on anti-depressants, a score \>5.
• Monoamineoxidase (MAO)inhibitors, and/or anti-psychotic medications.

Sponsors & Collaborators

• Genzyme, a Sanofi Company: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, United States

Location

Related Publications (1)

• Christine CW, Starr PA, Larson PS, Eberling JL, Jagust WJ, Hawkins RA, VanBrocklin HF, Wright JF, Bankiewicz KS, Aminoff MJ. Safety and tolerability of putaminal AADC gene therapy for Parkinson disease. Neurology. 2009 Nov 17;73(20):1662-9. doi: 10.1212/WNL.0b013e3181c29356. Epub 2009 Oct 14.

  PMID: 19828868 BACKGROUND

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

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

Study Officials

• Medical Monitor

  Genzyme, a Sanofi Company

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2005
• First Posted: September 30, 2005
• Study Start: November 1, 2004
• Primary Completion: March 1, 2013
• Study Completion: March 1, 2013
• Last Updated: December 4, 2013

Record last verified: 2013-12

Locations

US (1)