- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02926066
A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion
A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion (NTUH-AADC-011)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
AAV2-hAADC will be made by a GMP laboratory. An MRI will be performed to define the brain structure, and then metal nails will be fixed on the skull and a CT will be performed. The two images will be confined and the direction and depth of infusion will be determined. During the surgery, a stereotactic device will be implanted on both sides of the brain on a bur hole. Each putamen will be injected for two times. If there is no complication from the surgery, the patients will enter the follow up period.
In Cohort 1, subjects for high dose (2.37x10^11 vg) will be enrolled via sequential enrollment with an observation for 2 months or even longer. Only after a subject passing peak dyskinesia, which is indicated by a reduced drug dose required for alleviation of dyskinesia, or improved food intake, and being verified by Safety Committee, treatment for the next patient with high dose can be proceeded.
In Cohort 2, in order to be compared with Phase I/II (n=10), 4 patients will be treated in Cohort 2 and all of them will use the high dose (2.37x10^11 vg). Patients older than 3 (no more than 2 patients) years of age will be enrolled via sequential enrollment with an observation for 2 months or longer. Only after a subject passing peak dyskinesia, which is indicated by a reduced drug dose required for alleviation of dyskinesia, or improved food intake, which has been verified by the Safety Committee can the treatment at a high dose begin in the next patient older than 3.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Taipei, Taiwan, 100
- National Taiwan University Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- With a confirmed diagnosis of AADC, including cerebrospinal fluid analysis to show reduced levels of neurotransmitter metabolites, HVA and 5-HIAA, and higher L-Dopa, or with more than one mutation within AADC gene, etc.
- Classical clinical characteristics of AADC deficiency, such as oculogyric crises, hypotonia and developmental retardation.
- The child patient has to be over 2 years old or a thickness of skull enough for surgery.
- The child patient has to be under 6 years old (72 months) before being treated with study drugs.
- Participating patients must cooperate completely for all evaluations and examinations before, during and after the whole trial.
- Parents or guardians must sign to agree on this informed consent.
Exclusion criteria:
- Significant brain structure abnormality determined by the physician.
- Patients with any health or neurological doubts that may increase the risk of surgery cannot join this trial. PI has the right to evaluate the feasibility of subjects for this trial based on his/her health condition.
- Patients with anti-AAV2 neutralizing antibody titer over 1,200 folds or an ELISA OD over 1 cannot be recruited into this trial.
- Subjects participating in this trial cannot take any medications that may affect this clinical trial, which do not apply to those drugs used at specified duration as mentioned in this protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: AAV2-hAADC
Dosage form: Aqueous solution Dose(s): 2.37x10^11 vg/case(High dose) Dosing schedule: Intracerebral infusion, single dose Mechanism of action (if known): supplement a gene defect Dosage form: Aqueous solution Dose(s): 1.81x10^11 vg/case(Standard dose) Dosing schedule: Intracerebral infusion, single dose Mechanism of action (if known): supplement a gene defect |
Dosage form: Aqueous solution Dose(s): 2.37x10^11 vg/case(High dose) Dosing schedule: Intracerebral infusion, single dose Mechanism of action (if known): supplement a gene defect Dosage form: Aqueous solution Dose(s): 1.81x10^11 vg/case(Standard dose) Dosing schedule: Intracerebral infusion, single dose Mechanism of action (if known): supplement a gene defect |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation of therapeutic effect
Time Frame: 13 months
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13 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluation for the treatment safety
Time Frame: 13 months
|
|
13 months
|
Evaluation of secondary therapeutic effects
Time Frame: 13 months
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13 months
|
Exploratory endpoint
Time Frame: 13 months
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13 months
|
Collaborators and Investigators
Collaborators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 201511036MIND
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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