Parkinson's DiseasePhase 1NCT00229736
A Study of AAV-hAADC-2 in Subjects With Parkinson's Disease
A Phase 1 study testing AAV-hAADC-2 in people with Parkinson's Disease, run by Genzyme, a Sanofi Company at 1 site in United States.
Trial summary
Safety Study in subjects with Parkinson's Disease Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Parkinson's Disease
- What is being tested?
- AAV-hAADC-2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2004to Mar 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Contraindication to magnetic resonance imaging (MRI).
- Neutralizing antibody titer to AAV-2 ≥ 1:1200.
- For pre-menopausal women: a positive (+) urine pregnancy test.
- Dopaminergic blocking agents within 30 days prior to the Baseline visit.
- Investigational agents within 12 weeks prior to the Baseline visit.
- Clinically active infection with adenovirus or herpes virus.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, San Francisco
San Francisco, California
About this study
Official title: A Phase1 Open Label Safety Study of Intrastriatal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase (AAV-hAADC-2) in Subjects With Parkinson's Disease [AAV-hAADC-2-003]
Safety Study in subjects with Parkinson's Disease
Read the detailed description
In a patient with Parkinson's disease, the part of the brain called the substantia nigra progressively loses the ability to send dopamine signals to the striatum.
To compensate for the loss of striatal dopamine, most patients take L-dopa, an approved drug which is converted to dopamine by an essential enzyme - AADC.
With time, however, the brain loses its remaining ability to convert L-dopa to dopamine and thus the drug becomes progressively less effective.
In the therapy being studied, the gene coding for the enzyme that converts L-dopa to dopamine (AADC) is inserted into a common, non-pathogenic virus (AAV) to which > 90% of humans have been exposed.
The AAV will help to transport the AADC into the brain cells.
AAV-hAADC-2, the investigational drug being studied, is injected into the striatum during a surgical procedure.
Patients who undergo the procedure would continue to take L-dopa; AAV-hAADC-2 is intended to provide, directly to the brain, the missing enzyme needed to convert L-dopa to dopamine.
- Conditions
- Parkinson's Disease
- Being tested
- AAV-hAADC-2
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV-hAADC-2Genetic
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-2Genetic
3 x 10^11 vector genomes (vg) of AAV-hAADC-2 in a single dose of 200 µL bilaterally infused over 4 striatal targets
| Study group | Role | What they receive |
|---|---|---|
| AAV-hAADC-2 (9x10^10 vector genomes) | Experimental | Not described Receives: Genetic: AAV-hAADC-2 |
| AAV-hAADC-2 (3x10^11 vector genomes) | Experimental | Not described Receives: Genetic: AAV-hAADC-2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Time of treatment through Month 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2005 (estimated)
- Study startNov 2004
- Primary completionMar 2013
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Parkinson's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Genzyme, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, Study director, Genzyme, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00229736
- Sponsor's protocol ID
- AAVhAADC2003
- Status last verified
- Dec 2013
- First submitted
- 28 Sep 2005
- Last updated
- 4 Dec 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 19828868
Study at a glance
From the registry record, last updated by the sponsor on 4 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase1 Open Label Safety Study of Intrastriatal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase (AAV-hAADC-2) in Subjects With Parkinson's Disease [AAV-hAADC-2-003]
- ClinicalTrials.gov ID
- NCT00229736
- Acronym / sponsor ID
- AAVhAADC2003
- Conditions
- Parkinson's Disease
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Genzyme, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Nov 2004
- Primary completion
- Mar 2013 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 30 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Safety Study in subjects with Parkinson's Disease
Detailed description
In a patient with Parkinson's disease, the part of the brain called the substantia nigra progressively loses the ability to send dopamine signals to the striatum.
To compensate for the loss of striatal dopamine, most patients take L-dopa, an approved drug which is converted to dopamine by an essential enzyme - AADC.
With time, however, the brain loses its remaining ability to convert L-dopa to dopamine and thus the drug becomes progressively less effective.
In the therapy being studied, the gene coding for the enzyme that converts L-dopa to dopamine (AADC) is inserted into a common, non-pathogenic virus (AAV) to which > 90% of humans have been exposed.
The AAV will help to transport the AADC into the brain cells.
AAV-hAADC-2, the investigational drug being studied, is injected into the striatum during a surgical procedure.
Patients who undergo the procedure would continue to take L-dopa; AAV-hAADC-2 is intended to provide, directly to the brain, the missing enzyme needed to convert L-dopa to dopamine.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AAV-hAADC-2 (9x10^10 vector genomes) | Experimental | Genetic: AAV-hAADC-2 |
| AAV-hAADC-2 (3x10^11 vector genomes) | Experimental | Genetic: AAV-hAADC-2 |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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).
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AAV-hAADC-29 x 10^10 vector genomes (vg) of AAV-hAADC-2 in a single dose of 200 µL bilaterally infused over 4 striatal targets | Genetic | AAV-hAADC-2 (9x10^10 vector genomes) |
| AAV-hAADC-23 x 10^11 vector genomes (vg) of AAV-hAADC-2 in a single dose of 200 µL bilaterally infused over 4 striatal targets | Genetic | AAV-hAADC-2 (3x10^11 vector genomes) |
Primary outcome
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 frame: Time of treatment through Month 60.
2 secondary outcomes
The effect of AAV-hAADC-2 on clinical status as recorded in subject diaries, by clinical assessment, and daily levodopa requirement.
Time frame: 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 frame: Time of treatment through Month 60
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Dec 2013.
- Background: PubMed 19828868Christine 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor study director
Genzyme, a Sanofi Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AAV-hAADC-2 in people with Parkinson's Disease, run by Genzyme, a Sanofi Company at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Dec 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 frame: Time of treatment through Month 60.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00229736, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2013.