Aromatic Amino Acid Decarboxylase DeficiencyPhase 2NCT02926066
A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion
A Phase 2 study testing AAV2-hAADC in people with Aromatic Amino Acid Decarboxylase Deficiency, run by National Taiwan University Hospital at 1 site in Taiwan.
Trial summary
This clinical trial expansion is to offer patients, who are not enrolled into the Phase I/II trial, a chance of treatment, to provide the experience in this gene therapy, and to increase the dose slightly. Read more about this study
- Who is it for?
- Ages Up to 6 years
- Conditions the study is for
- Aromatic Amino Acid Decarboxylase Deficiency
- What is being tested?
- AAV2-hAADC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteTaiwan
- Study dates
- 9 Nov 2016to 16 May 2022
- Phase
- Phase 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 Up to 6 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion (NTUH-AADC-011)
This clinical trial expansion is to offer patients, who are not enrolled into the Phase I/II trial, a chance of treatment, to provide the experience in this gene therapy, and to increase the dose slightly.
Read the 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.
- Being tested
- AAV2-hAADC
- Keywords
- Aromatic L-amino acid decarboxylase (AADC)
- Medical subject headings
- Aromatic amino acid decarboxylase deficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AAV2-hAADCDrug
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
| Study group | Role | What they receive |
|---|---|---|
| AAV2-hAADC | Experimental | 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 Receives: Drug: AAV2-hAADC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluation of therapeutic effect
- At one year post-surgery, neurotransmitter metabolites (HVA or HIAA) increased in the CSF (compared to the pre-surgery (Baseline) level).
- At one year post-surgery, PDMS-II score is higher than that at pre-surgery (Baseline), with an improvement over 10 points.
Measured: 13 months
Secondary outcomes (3)
Evaluation for the treatment safety
- The absence of intracranial bleeding, which requires surgical management, after the surgery
- Craniotomy-induced CSF exudation
- The severity of post-surgery dyskinesia (if feeding is affected and then nasogastric tube is required)
- Incidence of other severe adverse events (information of adverse events of all kinds and severities will be collected, including treatment-emergent adverse events).
Measured: 13 months
Evaluation of secondary therapeutic effects
- Weight gain
- Increased signal intensity of dopamine in putamen during PET imaging
- Increased score in other development evaluations
Measured: 13 months
Exploratory endpoint
- The correlation between AAV2 antibody titer and therapeutic effect
- The correlation between subject's age and therapeutic effect
Measured: 13 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2016 (estimated)
- Study start9 Nov 2016
- Primary completion24 Jan 2022
- Study completion16 May 2022
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 Aromatic Amino Acid Decarboxylase DeficiencyStudies of the same condition, open and under way.
- More trials run by National Taiwan University HospitalThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Taiwan University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- PTC Therapeutics
- Responsible party
- Sponsor
- Investigators
- Yin-Hsiu Chien, MD.,PhD, Principal investigator, National Taiwan University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02926066
- Sponsor's protocol ID
- 201511036MIND
- Status last verified
- Nov 2022
- First submitted
- 3 Oct 2016
- Last updated
- 10 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Tai CH, Lee NC, Chien YH, Byrne BJ, Muramatsu SI, Tseng SH, Hwu WL. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022 Feb 2;30(2):509-518. doi: 10.1016/j.ymthe.2021.11.005. Epub 2021 Nov 8.
PubMed 34763085
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion (NTUH-AADC-011)
- ClinicalTrials.gov ID
- NCT02926066
- Acronym / sponsor ID
- 201511036MIND
- Keywords
- Aromatic L-amino acid decarboxylase (AADC)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- National Taiwan University HospitalUniversity, hospital or other
- Collaborators
- PTC Therapeutics
- Study start
- 9 Nov 2016 (actual)
- Primary completion
- 24 Jan 2022 (actual)
- Study completion
- 16 May 2022 (actual)
- First posted
- 6 Oct 2016 (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.
This clinical trial expansion is to offer patients, who are not enrolled into the Phase I/II trial, a chance of treatment, to provide the experience in this gene therapy, and to increase the dose slightly.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| AAV2-hAADC | Experimental | Drug: AAV2-hAADCDosage 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 |
Who may qualify
- Ages
- Up to 6 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
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 |
|---|---|---|
| AAV2-hAADCDosage 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 | Drug | AAV2-hAADC |
Primary outcome
Evaluation of therapeutic effect
Time frame: 13 months
1. At one year post-surgery, neurotransmitter metabolites (HVA or HIAA) increased in the CSF (compared to the pre-surgery (Baseline) level). 2. At one year post-surgery, PDMS-II score is higher than that at pre-surgery (Baseline), with an improvement over 10 points.
3 secondary outcomes
Evaluation for the treatment safety
Time frame: 13 months
Evaluation of secondary therapeutic effects
Time frame: 13 months
Exploratory endpoint
Time frame: 13 months
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 10 Feb 2023.
- Derived from this study: PubMed 34763085Tai CH, Lee NC, Chien YH, Byrne BJ, Muramatsu SI, Tseng SH, Hwu WL. Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency. Mol Ther. 2022 Feb 2;30(2):509-518. doi: 10.1016/j.ymthe.2021.11.005. Epub 2021 Nov 8.
- 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.
Yin-Hsiu Chien, MD.,PhD principal investigator
National Taiwan University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AAV2-hAADC in people with Aromatic Amino Acid Decarboxylase Deficiency, run by National Taiwan University Hospital at 1 site in Taiwan.
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 6 inclusion and 4 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 10 Feb 2023. 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 Taiwan. 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 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 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?
Evaluation of therapeutic effect (time frame: 13 months). 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 NCT02926066, 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 10 Feb 2023.