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Parkinson's DiseasePhase 1AADCNCT01973543

Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson's Disease

A Phase 1 study testing VY-AADC01 in people with Parkinson's Disease, run by Neurocrine Biosciences at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Safety study of AADC gene transfer (VY-AADC01) in subjects with Parkinson's disease. Read more about this study

Who is it for?
Ages 40 to 70 years
Conditions the study is for
Parkinson's Disease
What is being tested?
VY-AADC01
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
2 sitesUnited States
Study dates
Oct 2013to 24 Jan 2020
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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diagnosed with idiopathic Parkinson's disease
  • Disease duration of at least 5 years or more
  • Adequate duration of levodopa therapy
  • Modified Hoehn and Yahr Staging of at least 2.5 in the OFF state
  • Candidate for surgical intervention because of disabling motor complications.
  • UPDRS Part III (total motor) score ≥ 25 and a maximum of 60 in the OFF state.
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  • Unequivocal responsiveness to dopaminergic therapy.
  • Stable Parkinson's symptoms and medication regimen for at least 4 weeks prior to screening examination.
  • Ability to comprehend and sign the informed consent.
  • Normal Laboratory values prior to surgery.
  • Neutralizing AAV2 antibody titer ≤ 1:1200
  • Ability to travel to study visits alone or able to designate a caregiver.
  • Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist).
  • Subject agrees to not participate in any other therapeutic intervention study for 12 months after surgery.
  • Subject agrees to not have any vaccinations within 30 days of surgery.

Who cannot join

  • Atypical or secondary parkinsonism, including but not limited to symptoms believed to be due to trauma, brain tumor, infection, cerebrovascular disease, other neurological disease, or to drugs, chemicals or toxins.
  • Presence of dementia as defined by a Mattis Dementia Rating Scale-Second Edition (MDRS-2) of less than 130 at screening.
  • Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the investigators to be related to Parkinson's medications.
  • Presence of severe depression as measured by Beck Depression Inventory II (BDI-II) > 28 or a history of a major affective disorder within 5 years of screening examination.
  • Current suicidal ideation or suicide attempt within 5 years of screening examination.
  • History of substance abuse within 2 years of screening examination.
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  • Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery.
  • Contraindication to MRI and/or gadoteridol.
  • Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet prior to surgery.
  • Prior brain surgery including deep brain stimulation, infusion therapies or any other brain surgery.
  • Prior gene transfer.
  • History of stroke, poorly controlled or significant cardiovascular disease, diabetes or any other acute or chronic medical condition.
  • History of malignancy other than treated carcinoma in situ within three years of screening evaluation.
  • Clinically apparent or laboratory-detected infection.
  • Prior or current treatment with any investigational agent within 2 months of screening evaluation.
  • Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy and chemotherapy.
  • Pregnant and lactating women.
  • Subject with reproductive capacity who is unwilling to use barrier contraception.
  • Any medical condition that is likely to lead to disability during the course of the study and interfere with confound study assessments
  • Any factors, medical, or social, which would likely cause the subject to be unable to follow the study protocol, including geographical inaccessibility.
  • Ongoing treatments such as, neuroleptic medications, apomorphine, or levodopa infusion therapy (Duodopa®).

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • University of California, San Francisco

    San Francisco, California, 94143

Other trials in United States

About this study

Official title: An Open-label Safety and Efficacy Study of VY-AADC01 Administered by MRI-Guided Convective Infusion Into the Putamen of Subjects With Parkinson's Disease With Fluctuating Responses to Levodopa

Safety study of AADC gene transfer (VY-AADC01) in subjects with Parkinson's disease.

Read the detailed description

Parkinson's disease is a neurodegenerative disorder involving loss of neurons that release dopamine in the striatum. To compensate for the loss of dopamine, patients are typically prescribed levodopa medication which is converted to dopamine by the enzyme Aromatic L-Amino Acid Decarboxylase (AADC). As Parkinson's disease progresses, levodopa therapy becomes less effective and is associated with motor fluctuations, involuntary movements and other complications.

This study will primarily investigate the safety of increasing AADC levels in the striatum via AADC gene delivery. The hAADC gene is packaged into a gene transfer vector derived from a common, non-pathogenic virus (AAV2) to which >90% of humans have been exposed. This investigational drug, termed VY-AADC01, will be injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery.

Subjects will continue to take Parkinson's disease medications, including levodopa.

The safety and potential clinical responses to VY-AADC01 will be assessed by repeated clinical evaluations of Parkinson's disease, cognitive tests, laboratory blood tests and neuroimaging. Clinical evaluations will be performed over a 3 year follow-up period. A test to specifically assess the clinical response to levodopa will be performed once before AADC gene delivery and approximately 6 months after.

Being tested
VY-AADC01
Keywords
PD, Parkinson's disease, Aromatic Amino Acid Decarboxylase, AADC, AAV2-AADC, AAV2, Viral Vector, Gene Therapy, Gene Transfer, MRI, PET, VY-AADC01
Medical subject headings
Parkinson Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VY-AADC01Biological

    Also called AAV2-hAADC

    Neurosurgical delivery of VY-AADC01 to the brain.

Study groups in NCT01973543
Study groupRoleWhat they receive
VY-AADC01 Dose 1Experimental7.5 x 10^11 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Receives: Biological: VY-AADC01
VY-AADC01 Dose 2Experimental1.5 x 10^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Receives: Biological: VY-AADC01
VY-AADC01 Dose 3Experimental4.7x 10^12 vector genomes of VY-AADC01; Single dose, neurosurgically infused, bilaterally into the striatum.
Receives: Biological: VY-AADC01

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of AADC Gene Transfer

    Safety and Tolerability of AADC Gene Transfer assessed by Adverse Events and Serious Adverse Events.

    Measured: 3 Years after Gene Transfer

Secondary outcomes (2)

  1. Parkinson's Symptoms

    Effect of AAV2-hAADC on Parkinson's symptoms as recorded in subject diaries, neurological, motor, and non-motor assessments, quality of life surveys and changes to Parkinson's medications.

    Measured: 3 Years after Gene Transfer

  2. PET Scan Imaging

    Relationship between AAV2 distribution in the brain and change in AADC expression as seen in PET imaging.

    Measured: 6 Months after Gene Transfer

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2013 (estimated)
  2. Study startOct 2013
  3. Primary completion24 Jan 2020
  4. Study completion24 Jan 2020

Resources

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
Model description
VY-AADC01
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01973543
Sponsor's protocol ID
PD-1101
Other IDs
1302-1209
Acronym
AADC
Status last verified
Feb 2020
First submitted
25 Oct 2013
Last updated
3 Mar 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Undecided

Publications

  • Christine CW, Richardson RM, Van Laar AD, Thompson ME, Fine EM, Khwaja OS, Li C, Liang GS, Meier A, Roberts EW, Pfau ML, Rodman JR, Bankiewicz KS, Larson PS. Safety of AADC Gene Therapy for Moderately Advanced Parkinson Disease: Three-Year Outcomes From the PD-1101 Trial. Neurology. 2022 Jan 4;98(1):e40-e50. doi: 10.1212/WNL.0000000000012952. Epub 2021 Oct 14.

    PubMed 34649873

  • Christine CW, Bankiewicz KS, Van Laar AD, Richardson RM, Ravina B, Kells AP, Boot B, Martin AJ, Nutt J, Thompson ME, Larson PS. Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease. Ann Neurol. 2019 May;85(5):704-714. doi: 10.1002/ana.25450. Epub 2019 Mar 26.

    PubMed 30802998

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing VY-AADC01 in people with Parkinson's Disease, run by Neurocrine Biosciences at 2 sites 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 15 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 3 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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?

Safety of AADC Gene Transfer (time frame: 3 Years after Gene Transfer). 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 NCT01973543, which also lists 2 linked publications.

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 3 Mar 2020.

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