ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 3 of 4 for:    "Aromatic amino acid decarboxylase deficiency"

A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02926066
Recruitment Status : Recruiting
First Posted : October 6, 2016
Last Update Posted : October 20, 2017
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:
This clinical trial expansion is to offer patients, who are not enrolled into the Phase I/II trial, a chance of treatment, to extend the experience in this gene therapy, and to increase the dosage slightly to waive the drug dilution procedure.

Condition or disease Intervention/treatment Phase
Aromatic Amino Acid Decarboxylase Deficiency Drug: AAV2-hAADC Phase 2

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, for patients designing to have high dose (2.37x10^11 vg), sequential enrollment will be applied. The patients need to be followed for 2 months or more until the severity of post-gene therapy dyskinesia decreases, judged by a decrease in dose of drugs used to decrease dyskinesia or an improvement in feeding. After the agreement of the Safety Committee, the next high-dose patient can be enrolled. In Cohort 2, only patients older than or equal to 3 years need sequential enrollment.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC - An Expansion (NTUH-AADC-011)
Study Start Date : September 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018


Arm Intervention/treatment
Experimental: AAV2-hAADC
Dosage form: Aqueous solutionDose(s): 2.371x1011 vg/case Dosing schedule: Intracerebral infusion, single doseMechanism of action (if known): supplement a gene defect
Drug: AAV2-hAADC
Dosage form: Aqueous solutionDose(s): 2.371x1011 vg/case Dosing schedule: Intracerebral infusion, single doseMechanism of action (if known): supplement a gene defect




Primary Outcome Measures :
  1. Increase of neurotransmitter metabolite HVA or HIAA levels in CSF one year after gene therapy. (Progress compare with baseline) [ Time Frame: 13 months ]
  2. Increase more than 10 points score of PDMS-II compare with baseline. [ Time Frame: 13 months ]

Secondary Outcome Measures :
  1. Post-surgery intracerebral hemorrhage didn't happen. [ Time Frame: 13 months ]
  2. Post-surgery CSF leakage of Craniotomy [ Time Frame: 13 months ]
  3. Severity of dyskinesia post-gene therapy (if NG tube feeding is required) [ Time Frame: 13 months ]
  4. 4. Incidence of other SAE (we will collect all AEs and their severity information, including treatment-emergent adverse events) [ Time Frame: 13 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   up to 6 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. A definitive diagnosis of AADC deficiency, such as a CSF study showing decreased levels of HVA, 5-HIAA, an elevated L-DOPA level or the presence of at least one AADC gene pathologic mutation etc.
  2. Typical clinical manifestations of the disease, such as oculogyric crisis, hypotonia and delayed development.
  3. Over 2 years of age, or having adequate skull thickness for surgery.
  4. The patient must not older than 72 months of age before gene therapy.
  5. Participating patient must be fully cooperative for assessments and tests conducted before and throughout the entire trial.
  6. The parents or guardians must sign the Informed Consent Form to give their consent.

Exclusion criteria

  1. Obvious brain structural change in the judgment of the investigator.
  2. The subject will be excluded if there is any health or neurological concern which might increase the risk of surgery. The principal investigator has the right to assess whether the subject is eligible for this trial based on the subject's health condition.
  3. Patients with anti-AAV2 antibody titer higher than 1,200, or >1 O.D. value by ELISA will be excluded.
  4. Subject participating in this trial must not take any drug that might compromise this clinical trial; except that the drugs mentioned in the protocol can be used for a specified period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02926066


Contacts
Contact: Yin-Hsiu Chien, Doctor +886 2 23123456 ext 71937 chienyh@ntu.edu.tw
Contact: Wuh-Liang Hwu, Doctor +886 2 23123456 ext 71938 hwuwlntu@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 100
Contact: Yin-Hsiu Chien, Doctor    +886 2 23123456 ext 71937    chienyh@ntu.edu.tw   
Contact: Wuh-Liang Hwu, Doctor    +886 2 23123456 ext 71938    hwuwlntu@ntu.edu.tw   
Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Yin-Hsiu Chien, Doctor National Taiwan University Hospital

Publications:

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02926066     History of Changes
Other Study ID Numbers: 201511036MIND
First Posted: October 6, 2016    Key Record Dates
Last Update Posted: October 20, 2017
Last Verified: October 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by National Taiwan University Hospital:
Aromatic L-amino acid decarboxylase (AADC)

Additional relevant MeSH terms:
Amino Acid Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Dopa Decarboxylase
Antiparkinson Agents
Anti-Dyskinesia Agents