Parkinson DiseasePhase 1/2NCT02418598
AADC Gene Therapy for Parkinson's Disease
A Phase 1/2 study testing Cohort1 and Cohort2 in people with Parkinson Disease, run by Jichi Medical University at 1 site in Japan.
Trial summary
The purpose of this study is to evaluate the safety, efficacy of intra-putaminal infusion of AAV-hAADC-2 (adeno-associated virus encoding human aromatic L-amino acid decarboxylase) by stereotaxic surgery in patients with advanced Parkinson's disease. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Cohort1 and Cohort2
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteJapan
- Study dates
- 14 Apr 2015to 31 Mar 2018
- Phase
- Phase 1/2
- 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 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with idiopathic Parkinson's disease meet diagnostic criteria for Specified Disease designated by the Ministry of Health, Labour and Welfare (1995) : the Research Committee of CNS Degenerative Disease, L-Dopa is effective in the early disease stage and no findings suggestive of CNS Degenerative Disease are found.
- Age ≤ 75 years at the time of medical treatment.
- Age at onset ≥ 35 years.
- Duration of L-dopa therapy ≥ 5 years.
- Hoehn and Yahr Stage IV in OFF state at the onset of medical treatment.
- Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale Part III (MDS-UPDRS-III), minimum motor score of 30 to a maximum motor score of 100 in OFF state.
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- Positive response to dopaminergic therapy as evidenced by remarkable improvement in MDS-UPDRS-III motor score between the defined "OFF" and "ON" state: a minimum 16 points improvement in the MDS-UPDRS-III after dopaminergic therapy.
- Patients who can undergo the stereotaxic surgery for Parkinson's disease due to the intolerable motor complication minimum score of 4 to a maximum score of 9 in the MDS-UPDRS-IV part B (diurnal fluctuation of symptom) , not responsive to optimal medical therapy.
- To be able to comply with the requirements, including the frequent clinical examination after medical treatment, in this study.
- To keep the therapeutic medicine for Parkinson's disease for at least 2 months prior to participation in this study.
- Written informed consent.
Who cannot join
- Patients who is suspected secondary / atypical parkinsonism based on the medical history of cerebral vascular disease, exposure to antipsychotic or toxic agents, and encephalitis or based on the symptom of Progressive supranuclear palsy, Pyramidal tract sign, autonomic sign, Dementia, Hallucination, Delusion and so on or based on the finding by magnetic resonance imaging (MRI) such as Lacunar infarct or atrophy of the midbrain tectum and atrophy of the pons and the cerebellum.
- Patients with history of 3 hours or more of intensive or violent dyskinesias in the past 6 months.
- Patients with previous the stereotaxy for Parkinson's disease (pallidotomy, thalamotomy, deep brain stimulation) .
- Mini-Mental State Examination (MMSE) ≤ 20 or patient with a diagnosis of dementia in the neuropsychological evaluation.
- Patients with medical history of Hallucination, Delusion, schizophrenia or affective disorder within 6 months of informed consent.
- Patients with history of significant cardiovascular disease including cerebrovascular accident.
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- Malignant neoplasm in the brain, clinically significant neurological disease (for example significant brain atrophy not consistent with age).
- History of other malignancy, with the exception of treated carcinoma cutaneum, within 5 years.
- Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg.
- Coagulopathy or need for anticoagulant therapy.
- Clinically significant immune dysfunction (for example, the case who require the use of immunosuppressive drugs).
- Geriatric Depression Scale (GDS) short scale ≥ 10 points, or if on antidepressant, the score > 5 points.
- On monoamine oxidase (MAO)-A inhibitors, or antipsychotic medications.
- Unable to scan MRI.
- Cases without abnormal finding in FMT-PET.
- Premenopausal female or male who desire impregnating a female (excluded: in case when sperm is cryopreserved prior to gene therapy and child is born by using the sperm).
- Past medical history of convulsive seizure within 3 years or receiving antiepileptic drug or patients with epileptic aberrance in the electroencephalography.
- Past medical history of serious drug allergy.
- Patients who have participated in other clinical trial within 6 months.
- Patients who meet any of the following criteria:
- Serious renal disorder ( Cr ≥ 2.0 mg/dl and BUN ≥ 25mg/dl)
- Serious hepatic disorder ( AST (GOT) / ALT (GPT) ≤2.5xupper limit of normal (ULN)
- Serious diabetes (casual blood glucose or fasting blood glucose ≥ 200 mg/dl and HbA1c ≥ 9 %)
- Any other patients judged by investigators to be inappropriate for the subject of this study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I /II Study of Intra-putaminal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase in Subjects With Parkinson's Disease
The purpose of this study is to evaluate the safety, efficacy of intra-putaminal infusion of AAV-hAADC-2 (adeno-associated virus encoding human aromatic L-amino acid decarboxylase) by stereotaxic surgery in patients with advanced Parkinson's disease.
Read the detailed description
Subjects will be hospitalized and conducted the baseline examination on Day -10. The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 200 / 600 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 / 150 µL per site) at a flow rate of 3 µL per minute on Day 0.
After the infusion is complete, the cannula devices will be removed, and the surgical incision will be seamed in accordance with usual trephination. After that, cranial CT scan will be performed so as to confirm whether there are complications such as the occurrence of intracranial bleeding or not. Subjects stay in a hospital for 14 days after infusion of AAV-hAADC-2.
Data and Safety Monitoring Board (DSMB) will be evaluated the safety and efficacy of all subjects at 6 months later assessment in low dose cohort. If there are no events relevant to the discontinuance criteria or moderate to severe adverse events with casual relationship, "Definitely related" or "Possibly related", to AAV-hAADC-2 in this cohort, the study moves to high dose cohort.
At the time of 6 months after the infusion, investigator assesses the treatment effect of AAV-hAADC-2 on the basis of subject diaries, clinical assessment and levodopa requirement dosage. At the same time, investigator assesses a relationship between the dose of AAV-hAADC-2 infused and the amount of intra-putaminal expression by FMT-PET imaging.
The investigator also assesses the safety for 5 years after the baseline examination. Long-term follow up study is additionally conducted for 10 years in reference to guideline of FDA.
- Conditions
- Parkinson Disease
- Being tested
- Cohort1, Cohort2
- Keywords
- Adeno-associated virus, Aromatic L-amino acid decarboxylase, AAV-hAADC-2, AAV-2, Gene Therapy, Gene Transfer, Parkinson Disease, Basal Ganglia Disease, Brain Disease
- Medical subject headings
- Parkinson Disease, Basal Ganglia Diseases, Brain Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort1Genetic
AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) administered in this cohort is 3x10^11 vg/subject.
Cohort2Genetic
AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) administered in this cohort is 9x10^11 vg/subject.
| Study group | Role | What they receive |
|---|---|---|
| Cohort1 | Experimental | The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 200 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 µL per site) at a flow rate of 3 µL per minute. Receives: Genetic: Cohort1 |
| Cohort2 | Experimental | The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 600 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 150 µL per site) at a flow rate of 3 µL per minute. Receives: Genetic: Cohort2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The safety of intra-putaminal infusion of AAV-hAADC-2 as measured by adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992).
Confirm the adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992).
Measured: 6 months
Secondary outcomes (2)
The treatment effect of intra-putaminal infusion of AAV-hAADC-2
Assess the improvement of Parkinson's symptom as recorded in the subject diaries, clinical assessment and requirement dosage of levodopa.
Measured: 6 months
The amount of intra-putaminal expression of AAV-hAADC-2
Assesses a relationship between the dose of AAV-hAADC-2 infused and the amount of intra-putaminal expression by FMT-PET imaging.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2015 (estimated)
- Study start14 Apr 2015
- Primary completion31 Mar 2018
- Study completion31 Mar 2018
Why it stopped: another clinical study for regulatory approval is planned
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jichi Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Takara Bio Inc., Gene Therapy Research Institution,Co.,Ltd.
- Responsible party
- Principal investigator, Shinichi Muramatsu, Jichi Medical University
- Investigators
- Shin-ichi Muramatsu, MD, PhD, Study chair, Division of Oriental Medicine, Center for Community Medicine, Jichi Medical University; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University; Division of Neurology, Department of Medicine, Jichi Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02418598
- Sponsor's protocol ID
- JMU-AAV-AADC-PD
- Status last verified
- Aug 2019
- First submitted
- 12 Apr 2015
- Last updated
- 9 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I /II Study of Intra-putaminal Infusion of Adeno-Associated Virus Encoding Human Aromatic L-Amino Acid Decarboxylase in Subjects With Parkinson's Disease
- ClinicalTrials.gov ID
- NCT02418598
- Acronym / sponsor ID
- JMU-AAV-AADC-PD
- Conditions
- Parkinson Disease
- Keywords
- Adeno-associated virus, Aromatic L-amino acid decarboxylase, AAV-hAADC-2, AAV-2, Gene Therapy, Gene Transfer, Parkinson Disease, Basal Ganglia Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: another clinical study for regulatory approval is planned
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Jichi Medical UniversityUniversity, hospital or other
- Collaborators
- Takara Bio Inc., Gene Therapy Research Institution,Co.,Ltd.
- Study start
- 14 Apr 2015 (actual)
- Primary completion
- 31 Mar 2018 (actual)
- Study completion
- 31 Mar 2018 (actual)
- First posted
- 16 Apr 2015 (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.
The purpose of this study is to evaluate the safety, efficacy of intra-putaminal infusion of AAV-hAADC-2 (adeno-associated virus encoding human aromatic L-amino acid decarboxylase) by stereotaxic surgery in patients with advanced Parkinson's disease.
Detailed description
Subjects will be hospitalized and conducted the baseline examination on Day -10. The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 200 / 600 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 / 150 µL per site) at a flow rate of 3 µL per minute on Day 0.
After the infusion is complete, the cannula devices will be removed, and the surgical incision will be seamed in accordance with usual trephination. After that, cranial CT scan will be performed so as to confirm whether there are complications such as the occurrence of intracranial bleeding or not. Subjects stay in a hospital for 14 days after infusion of AAV-hAADC-2.
Data and Safety Monitoring Board (DSMB) will be evaluated the safety and efficacy of all subjects at 6 months later assessment in low dose cohort. If there are no events relevant to the discontinuance criteria or moderate to severe adverse events with casual relationship, "Definitely related" or "Possibly related", to AAV-hAADC-2 in this cohort, the study moves to high dose cohort.
At the time of 6 months after the infusion, investigator assesses the treatment effect of AAV-hAADC-2 on the basis of subject diaries, clinical assessment and levodopa requirement dosage. At the same time, investigator assesses a relationship between the dose of AAV-hAADC-2 infused and the amount of intra-putaminal expression by FMT-PET imaging.
The investigator also assesses the safety for 5 years after the baseline examination. Long-term follow up study is additionally conducted for 10 years in reference to guideline of FDA.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort1 | Experimental | Genetic: Cohort1The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 200 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 50 µL per site) at a flow rate of 3 µL per minute. |
| Cohort2 | Experimental | Genetic: Cohort2The target putamen for AAV-hAADC-2 infusion is identified on MRI image that has been taken prior to the operation, and then subjects will be bilaterally infused with a total volume of 600 µL at a total of 4 sites (2 sites in left putamen, 2 sites in right putamen; 150 µL per site) at a flow rate of 3 µL per minute. |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients with idiopathic Parkinson's disease meet diagnostic criteria for Specified Disease designated by the Ministry of Health, Labour and Welfare (1995) : the Research Committee of CNS Degenerative Disease, L-Dopa is effective in the early disease stage and no findings suggestive of CNS Degenerative Disease are found.
- Age ≤ 75 years at the time of medical treatment.
- Age at onset ≥ 35 years.
- Duration of L-dopa therapy ≥ 5 years.
- Hoehn and Yahr Stage IV in OFF state at the onset of medical treatment.
Key exclusion criteria (24 listed)
- Patients who is suspected secondary / atypical parkinsonism based on the medical history of cerebral vascular disease, exposure to antipsychotic or toxic agents, and encephalitis or based on the symptom of Progressive supranuclear palsy, Pyramidal tract sign, autonomic sign, Dementia, Hallucination, Delusion and so on or based on the finding by magnetic resonance imaging (MRI) such as Lacunar infarct or atrophy of the midbrain tectum and atrophy of the pons and the cerebellum.
- Patients with history of 3 hours or more of intensive or violent dyskinesias in the past 6 months.
- Patients with previous the stereotaxy for Parkinson's disease (pallidotomy, thalamotomy, deep brain stimulation) .
- Mini-Mental State Examination (MMSE) ≤ 20 or patient with a diagnosis of dementia in the neuropsychological evaluation.
- Patients with medical history of Hallucination, Delusion, schizophrenia or affective disorder within 6 months of informed consent.
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 |
|---|---|---|
| Cohort1AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) administered in this cohort is 3x10^11 vg/subject. | Genetic | Cohort1 |
| Cohort2AAV-hAADC-2 is administered via bilateral intra-putaminal infusion. The number of vector genomes (vg) administered in this cohort is 9x10^11 vg/subject. | Genetic | Cohort2 |
Primary outcome
The safety of intra-putaminal infusion of AAV-hAADC-2 as measured by adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992).
Time frame: 6 months
Confirm the adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992).
2 secondary outcomes
The treatment effect of intra-putaminal infusion of AAV-hAADC-2
Time frame: 6 months
The amount of intra-putaminal expression of AAV-hAADC-2
Time frame: 6 months
Results and safety
The study was stopped early (reason given: another clinical study for regulatory approval is planned). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2019.
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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.
Shin-ichi Muramatsu, MD, PhD study chair
Division of Oriental Medicine, Center for Community Medicine, Jichi Medical University; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University; Division of Neurology, Department of Medicine, Jichi Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Cohort1 and Cohort2 in people with Parkinson Disease, run by Jichi Medical University at 1 site in Japan.
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 11 inclusion and 24 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: stopped early, as of the sponsor's last update on 9 Aug 2019. 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 Japan. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was stopped early (reason given: another clinical study for regulatory approval is planned). Results are not available in the source record.
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 of intra-putaminal infusion of AAV-hAADC-2 as measured by adverse events (including Abnormal laboratory test results) with Classification criteria for severity of adverse reactions (dated 29th Jun,1992). (time frame: 6 months). 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 9 Aug 2019.