Idiopathic Parkinson's DiseasePhase 1NCT03065192
Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease
A Phase 1 study testing VY-AADC01 in people with Idiopathic Parkinson's Disease and Parkinson's Disease, run by Neurocrine Biosciences at 4 sites in United States.
Trial summary
Safety and efficacy of AADC gene transfer in participants with Parkinson's disease. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Idiopathic Parkinson's Disease, Parkinson's Disease, Basal Ganglia Disease
- What is being tested?
- VY-AADC01
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 4 sitesUnited States
- Study dates
- 11 May 2017to 10 Aug 2021
- 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
- Diagnosed with idiopathic PD.
- Adequate duration of levodopa therapy.
- Disease duration of at least 5 years or more.
- Modified Hoehn \& Yahr Staging with at least 2.5 hours or more in the OFF state.
- Candidate for surgical intervention because of disabling motor complications.
- UPDRS Part III (total score) of at least 25 in the OFF state.
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- Unequivocal responsiveness to dopaminergic therapy.
- Stable Parkinson's symptoms and medications for at least 4 weeks prior to screening evaluation.
- Ability to comprehend and sign the informed consent.
- Normal laboratory values prior to surgery.
- Medically and mentally capable of undergoing and complying with the surgical procedure and protocol requirements.
- 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).
- Approved by the Eligibility Review Committee.
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) score of less than 130 at screening.
- Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the Investigator to be related to Parkinson's medications.
- Presence of severe depression, as indicated by a BDI-II score greater than 28, or a history of a major affective disorder within 5 years of screening evaluation.
- Active suicidal ideation or suicide attempt within 5 years of screening evaluation.
- History of substance abuse within 2 years of screening evaluation.
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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 therapy prior to surgery.
- Prior brain surgery including lesioning procedures, 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 3 years of screening evaluation.
- Clinically apparent or laboratory-detected infection.
- Prior or current treatment with any investigational agent within 2 months of screening evaluation.
- Inability to comply with the procedures of the protocol, including completion of paper Parkinson's disease diaries, frequent and prolonged study visits including off medication visits, and travel.
- Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy, and chemotherapy.
- Any serious medical condition or abnormal finding on physical examination or laboratory investigation that would substantially increase the risks of the study procedures.
- Any medical condition that is likely to lead to disability during the course of the study and interfere with or confound study assessments.
- Pregnant and lactating women.
- Male or female with reproductive capacity who is unwilling to use barrier contraception for 6 months after surgery.
- Plans to receive any vaccination within 30 days of surgery.
- Any factors, medical or social, which would likely cause the participant to be unable to follow the study protocol, including geographical inaccessibility.
- Ongoing treatments including neuroleptic medications, apomorphine, or levodopa infusion therapy (Duopa®).
- Plans to participate in any other therapeutic intervention study within 12 months after surgery.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30322
Ohio State University (OSU)
Columbus, Ohio, 43210
University of Pittsburgh Medical Center (UPMC)
Pittsburgh, Pennsylvania, 15213
University of California, San Francisco (UCSF)
San Francisco, California, 94143
About this study
Official title: An Open-label Safety and Efficacy Study of VY-AADC01 Administered by MRI-Guided Convective Infusion Using a Posterior Trajectory Into the Putamen of Participants With Parkinson's Disease With Fluctuating Responses to Levodopa
Safety and efficacy of AADC gene transfer in participants with Parkinson's disease.
Read the detailed description
Parkinson's disease (PD) is a neurodegenerative disorder involving loss of dopamine producing neurons located in the striatum. Levodopa is the primary treatment used to treat Parkinson's disease, which converts to dopamine by the enzyme (protein) Aromatic L-Amino Acid Decarboxylase (AADC). As PD progresses, the amount of AADC levels in the brain decreases, and in turn, reduces the amount of dopamine that is produced with each dose of levodopa.
The primary objective of this study is to evaluate the safety of increasing AADC levels, via gene delivery. The investigational drug, termed VY-AADC-01, will be injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery.
Participants will continue to take their Parkinson medications, including levodopa while participating in this study.
The safety and potential clinical responses to VY-AADC-01 will be assessed by repeated clinical evaluations of Parkinson's disease, treatment review phone calls, cognitive tests, laboratory blood tests, patient reported outcomes scales, patient diaries, collection of adverse events, and neuro-imaging. Clinical evaluations will be performed over a 3 year follow-up period.
- Conditions
- Idiopathic Parkinson's Disease, Parkinson's Disease, Basal Ganglia Disease, Brain Diseases, Central Nervous System Diseases, Movement Disorders
- Being tested
- VY-AADC01
- Keywords
- Gene Therapy, PD, Parkinson's Disease, Aromatic L- Amino Acid Decarboxylase, AADC, AAV2-AADC, AAV2, Viral Vector, Gene Transfer, MRI, PET, VY-AADC01
- Medical subject headings
- Parkinson Disease, Basal Ganglia Diseases, Brain Diseases, Central Nervous System Diseases, Movement Disorders, Nervous System Diseases, Neurodegenerative Diseases, Parkinsonian Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VY-AADC01Drug
Single dose, neurosurgically infused, bilaterally into the striatum.
| Study group | Role | What they receive |
|---|---|---|
| VY-AADC01 Single Dose | Experimental | 9.4 x 10^12 vector genomes of VY-AADC01 Receives: Drug: VY-AADC01 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grading of adverse Events/Serious Adverse Events (AE's/SAE's)
Grading will be assessed using NCI CTCAE, version 4.03.
Measured: Baseline to 3 Years After Gene Transfer
Magnetic Resonance Imaging (MRI)
Safety of VY-AADC01 will be assessed by any clinically significant abnormalities on MRI scans as compared to Baseline.
Measured: Baseline to 3 Years After Gene Transfer
Routine physical examinations
Safety of VY-AADC01 will be assessed by routine physical examinations.
Measured: Baseline to 3 Years After Gene Transfer
Routine clinical laboratory analysis
Safety of VY-AADC01 will be assessed by routine clinical laboratory analysis.
Measured: Baseline to 3 Years After Gene Transfer
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) results
C-SSRS is a standardized suicidal rating system.
Measured: Baseline to 3 Years After Gene Transfer
Secondary outcomes (16)
Change in Parkinson's medications
Change in Parkinson's medications compared to Baseline.
Measured: Baseline to 3 Years After Gene Transfer
Change in motor function using Parkinson Disease Diaries
Diary used to assess changes in PD motor symptoms.
Measured: Baseline to 3 Years After Gene Transfer
Change in motor function using a Stand-Walk-Sit Test
Standardized test used in PD studies to assess functional mobility.
Measured: Baseline to 3 Years After Gene Transfer
Change in motor function using Modified Hoehn and Yahr Scale
Scale used to measure overall level of disability due to PD.
Measured: Baseline to 3 Years After Gene Transfer
Change in motor function using Unified Parkinson's Disease Rating Scale (UPDRS)
Standard assessment scale used to quantify signs and symptoms of PD.
Measured: Baseline to 3 Years After Gene Transfer
Change in occurrence of dyskinesia using Unified Dyskinesia Rating Scale (UDysRS)
Comprehensive rating tool used to assess essential features of dyskinesia in PD.
Measured: Baseline to 3 Years After Gene Transfer
Change in mood using Beck Depression Inventory II (BDI-II)
Self-administered measure of depression symptoms.
Measured: Baseline to 3 Years After Gene Transfer
Change in cognitive function using Modified Cognitive Assessment (MoCA)
Rapid screening instrument for mild cognitive dysfunction.
Measured: Baseline to 3 Years After Gene Transfer
Change in cognitive function using Mattis Dementia Rating Scale - Second Edition (MDRS-2)
Standardized neuropsychological test battery to measure dementia.
Measured: Baseline to 3 Years After Gene Transfer
Change in compulsive behavior using the Questionnaire Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
Rating scale to quantify the severity of a variety of compulsive disorders and behaviors.
Measured: Baseline to 3 Years After Gene Transfer
Change in sleep quality and disturbance using the Parkinson's Disease Sleep Scale 2 (PDSS-2)
Visual analogue scale addressing 15 commonly reported symptoms associated with sleep disturbance in PD.
Measured: Baseline to 3 Years After Gene Transfer
Change in Non-Motor System Scale (NMSS)
Standard rating scale that assesses the non-motor symptoms that may be associated with PD.
Measured: Baseline to 3 Years Gene Transfer
Change in quality of life using Parkinson's Disease Questionnaire (PDQ39)
Validated questionnaire to measure health related quality of life in PD patients.
Measured: Baseline to 3 Years After Gene Transfer
Change in quality of life using Schwab and England Scale
PD specific disability scale used to express the levels of independence with activities of daily living.
Measured: Baseline to 3 Years After Gene Transfer
Change in quality of life using in Clinical Global Impression Scale (CGI)
Scale used to assess treatment response in psychiatric patients.
Measured: Baseline to 3 Years After Gene Transfer
Change in quality of life using Patient Global Impression Scale (PGI)
Scale used to assess participants improvement in their PD symptoms.
Measured: Baseline to 3 Years After Gene Transfer
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2017
- Study start11 May 2017
- Primary completion10 Aug 2021
- Study completion10 Aug 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Parkinson's DiseaseStudies of the same condition, open and under way.
- More trials run by Neurocrine BiosciencesThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neurocrine Biosciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Voyager Therapeutics
- Responsible party
- Sponsor
- Investigators
- Steve Hersch, MD, Study director, Voyager Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03065192
- Sponsor's protocol ID
- PD-1102
- Status last verified
- Mar 2022
- First submitted
- 10 Feb 2017
- Last updated
- 21 Mar 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Safety and Efficacy Study of VY-AADC01 Administered by MRI-Guided Convective Infusion Using a Posterior Trajectory Into the Putamen of Participants With Parkinson's Disease With Fluctuating Responses to Levodopa
- ClinicalTrials.gov ID
- NCT03065192
- Acronym / sponsor ID
- PD-1102
- Conditions
- Idiopathic Parkinson's Disease, Parkinson's Disease, Basal Ganglia Disease, Brain Diseases, Central Nervous System Diseases, Movement Disorders
- Keywords
- Gene Therapy, PD, Parkinson's Disease, Aromatic L- Amino Acid Decarboxylase, AADC, AAV2-AADC, AAV2, Viral Vector
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Neurocrine BiosciencesIndustry (pharma, biotech, devices)
- Collaborators
- Voyager Therapeutics
- Study start
- 11 May 2017 (actual)
- Primary completion
- 10 Aug 2021 (actual)
- Study completion
- 10 Aug 2021 (actual)
- First posted
- 27 Feb 2017 (actual)
- 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 and efficacy of AADC gene transfer in participants with Parkinson's disease.
Detailed description
Parkinson's disease (PD) is a neurodegenerative disorder involving loss of dopamine producing neurons located in the striatum. Levodopa is the primary treatment used to treat Parkinson's disease, which converts to dopamine by the enzyme (protein) Aromatic L-Amino Acid Decarboxylase (AADC). As PD progresses, the amount of AADC levels in the brain decreases, and in turn, reduces the amount of dopamine that is produced with each dose of levodopa.
The primary objective of this study is to evaluate the safety of increasing AADC levels, via gene delivery. The investigational drug, termed VY-AADC-01, will be injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery.
Participants will continue to take their Parkinson medications, including levodopa while participating in this study.
The safety and potential clinical responses to VY-AADC-01 will be assessed by repeated clinical evaluations of Parkinson's disease, treatment review phone calls, cognitive tests, laboratory blood tests, patient reported outcomes scales, patient diaries, collection of adverse events, and neuro-imaging. Clinical evaluations will be performed over a 3 year follow-up period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VY-AADC01 Single Dose | Experimental | Drug: VY-AADC019.4 x 10^12 vector genomes of VY-AADC01 |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Diagnosed with idiopathic PD.
- Adequate duration of levodopa therapy.
- Disease duration of at least 5 years or more.
- Modified Hoehn \& Yahr Staging with at least 2.5 hours or more in the OFF state.
- Candidate for surgical intervention because of disabling motor complications.
Key exclusion criteria (25 listed)
- 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) score of less than 130 at screening.
- Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the Investigator to be related to Parkinson's medications.
- Presence of severe depression, as indicated by a BDI-II score greater than 28, or a history of a major affective disorder within 5 years of screening evaluation.
- Active suicidal ideation or suicide attempt within 5 years of screening evaluation.
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 |
|---|---|---|
| VY-AADC01Single dose, neurosurgically infused, bilaterally into the striatum. | Drug | VY-AADC01 Single Dose |
Primary outcome
Grading of adverse Events/Serious Adverse Events (AE's/SAE's)
Time frame: Baseline to 3 Years After Gene Transfer
Grading will be assessed using NCI CTCAE, version 4.03.
Magnetic Resonance Imaging (MRI)
Time frame: Baseline to 3 Years After Gene Transfer
Safety of VY-AADC01 will be assessed by any clinically significant abnormalities on MRI scans as compared to Baseline.
Routine physical examinations
Time frame: Baseline to 3 Years After Gene Transfer
Safety of VY-AADC01 will be assessed by routine physical examinations.
Routine clinical laboratory analysis
Time frame: Baseline to 3 Years After Gene Transfer
Safety of VY-AADC01 will be assessed by routine clinical laboratory analysis.
Change in Columbia-Suicide Severity Rating Scale (C-SSRS) results
Time frame: Baseline to 3 Years After Gene Transfer
C-SSRS is a standardized suicidal rating system.
16 secondary outcomes
Change in Parkinson's medications
Time frame: Baseline to 3 Years After Gene Transfer
Change in motor function using Parkinson Disease Diaries
Time frame: Baseline to 3 Years After Gene Transfer
Change in motor function using a Stand-Walk-Sit Test
Time frame: Baseline to 3 Years After Gene Transfer
Change in motor function using Modified Hoehn and Yahr Scale
Time frame: Baseline to 3 Years After Gene Transfer
Change in motor function using Unified Parkinson's Disease Rating Scale (UPDRS)
Time frame: Baseline to 3 Years After Gene Transfer
Change in occurrence of dyskinesia using Unified Dyskinesia Rating Scale (UDysRS)
Time frame: Baseline to 3 Years After Gene Transfer
Change in mood using Beck Depression Inventory II (BDI-II)
Time frame: Baseline to 3 Years After Gene Transfer
Change in cognitive function using Modified Cognitive Assessment (MoCA)
Time frame: Baseline to 3 Years After Gene Transfer
Change in cognitive function using Mattis Dementia Rating Scale - Second Edition (MDRS-2)
Time frame: Baseline to 3 Years After Gene Transfer
Change in compulsive behavior using the Questionnaire Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS)
Time frame: Baseline to 3 Years After Gene Transfer
Change in sleep quality and disturbance using the Parkinson's Disease Sleep Scale 2 (PDSS-2)
Time frame: Baseline to 3 Years After Gene Transfer
Change in Non-Motor System Scale (NMSS)
Time frame: Baseline to 3 Years Gene Transfer
Change in quality of life using Parkinson's Disease Questionnaire (PDQ39)
Time frame: Baseline to 3 Years After Gene Transfer
Change in quality of life using Schwab and England Scale
Time frame: Baseline to 3 Years After Gene Transfer
Change in quality of life using in Clinical Global Impression Scale (CGI)
Time frame: Baseline to 3 Years After Gene Transfer
Change in quality of life using Patient Global Impression Scale (PGI)
Time frame: Baseline to 3 Years After Gene Transfer
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 21 Mar 2022.
- Company WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Steve Hersch, MD study director
Voyager Therapeutics, Inc.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing VY-AADC01 in people with Idiopathic Parkinson's Disease and Parkinson's Disease, run by Neurocrine Biosciences at 4 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 14 inclusion and 25 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 21 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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?
Grading of adverse Events/Serious Adverse Events (AE's/SAE's) (time frame: Baseline to 3 Years After Gene Transfer). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Mar 2022.