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

NCT02926066 | Completed Phase 2 DMC

• 1 other identifier: 201511036MIND
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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 provide the experience in this gene therapy, and to increase the dose slightly.

Conditions

Aromatic Amino Acid Decarboxylase Deficiency

Keywords

Aromatic L-amino acid decarboxylase (AADC)

Outcome Measures

Primary Outcomes (1)

• Evaluation of therapeutic effect

  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.

  13 months

Secondary Outcomes (3)

• Evaluation for the treatment safety

  13 months

• Evaluation of secondary therapeutic effects

  13 months

• Exploratory endpoint

  13 months

Study Arms (1)

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

Drug: AAV2-hAADC

Interventions

AAV2-hAADC DRUG

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

AAV2-hAADC

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• PTC Therapeutics: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 34763085 DERIVED

MeSH Terms

Conditions

Aromatic amino acid decarboxylase deficiency

Study Officials

• Yin-Hsiu Chien, MD.,PhD

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 3, 2016
• First Posted: October 6, 2016
• Study Start: November 9, 2016
• Primary Completion: January 24, 2022
• Study Completion: May 16, 2022
• Last Updated: February 10, 2023

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)