A Phase I/II Clinical Trial for Treatment of Aromatic L-amino Acid Decarboxylase (AADC) Deficiency Using AAV2-hAADC

NCT01395641 | Completed Phase 1 DMC

• 1 other identifier: NTUH-AADC-010(200802042M)
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase I/II trial is to prove the efficacy and safety of AAV2-hAADC to treat patients with AADC deficiency.

Conditions

Aromatic L-amino Acid Decarboxylase (AADC) Deficiency

Keywords

Aromatic Amino Acid Decarboxylase; AADC; DDC; Gene Therapy; AAV2-AADC; Viral Vector; Gene Transfer; Aromatic L-Amino Acid Decarboxylase Deficiency

Outcome Measures

Primary Outcomes (1)

• Evaluation of therapeutic effect

  1. At one year post-surgery, neurotransmitter metabolites (HVA or HIAA) is detectable in CSF (higher than that at pre-surgery) 2. At one year post-surgery, PDMS-II score is higher than that at pre-surgery, with an improvement over 10 points

  12 months

Secondary Outcomes (3)

• Evaluation of safety and other therapeutic effects Evaluation for the treatment safety

  12 months

• Evaluation of secondary therapeutic effects

  5 years

• Exploratory endpoint

  5 years

Study Arms (1)

Gene therapy

EXPERIMENTAL

Intracerebral infusion of AAV2-hAADC viral vector will be performed

Drug: gene therapy

Interventions

gene therapy DRUG

AAV2-hAADC viral vector will be injected into bilateral putamen by stereotactic surgery.

Also known as: Intracerebral infusion of AAV2-hAADC viral vector

Gene therapy

Eligibility Criteria

• Age: 24 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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, together with more than one mutation within AADC gene.
• Classical clinical characteristics of AADC deficiency, such as oculogyric crises, hypotonia and developmental retardation.
• The sick child has to be over 2 years old or a head circumference big enough for surgery.
• 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
• 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.
• Since high-level neutralizing antibodies may disturb the therapeutic effect of gene therapy, patients with anti-AAV2 neutralizing antibody titer over 1,200 folds or an ELISA OD over 1 cannot be enrolled into this trial.
• Subjects enrolled in this clinical trial cannot take any medications that may affect this trial.

Sponsors & Collaborators

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

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Related Publications (2)

• 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

• Chien YH, Lee NC, Tseng SH, Tai CH, Muramatsu SI, Byrne BJ, Hwu WL. Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial. Lancet Child Adolesc Health. 2017 Dec;1(4):265-273. doi: 10.1016/S2352-4642(17)30125-6. Epub 2017 Oct 23.

  PMID: 30169182 DERIVED

MeSH Terms

Conditions

Aromatic amino acid decarboxylase deficiency

Interventions

Genetic Therapy

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques

Study Officials

• Wuh-Liang Hwu, M.D., Ph.D.

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2011
• First Posted: July 15, 2011
• Study Start: October 22, 2014
• Primary Completion: December 18, 2020
• Study Completion: March 7, 2022
• Last Updated: February 10, 2023

Record last verified: 2022-11

Locations

TW (1)