search
Back to results

Canavan-Single Patient IND

Primary Purpose

Canavan Disease

Status
No longer available
Phase
Locations
United States
Study Type
Expanded Access
Intervention
rAAV9-CB6-AspA
Sponsored by
University of Florida
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an expanded access trial for Canavan Disease focused on measuring Gene Therapy

Eligibility Criteria

18 Months - 24 Months (Child)Male

Inclusion Criteria:

  • Male
  • 18-24 months of age at time of study enrollment
  • Have a diagnosis of Canavan disease, as defined by biochemical criteria AND/OR genetic mutation analysis, AND demonstrate clinical findings such as macrocephaly, developmental delay, seizures or other positive findings
  • Elevated brain NAA levels, which is correlated with NAA acidemia and aciduria
  • Willing to discontinue aspirin, aspirin-containing products and other drugs that may alter platelet function 7 days prior to dosing, resuming 24 hours after the gene transfer agent has been administered

Exclusion Criteria:

  • Have required acute (as distinguished from long-term, maintenance or chronic suppressive) oral or intravenous antibiotic therapy for a respiratory infection within 15 days prior to screening
  • Have required oral or systemic corticosteroids within the last 15 days prior to baseline screening
  • Have a platelet count less than 75,000/mm3
  • Have history of platelet dysfunction, evidence of abnormal platelet function at screening, or history of recent use of drugs that may alter platelet function, which the subject is unable/unwilling to discontinue for study agent administration
  • Have an INR greater than 1.3
  • Have transaminases and alkaline phosphatase more than ten times the upper limit of normal at screening or Day-1; or an abnormal chemistry profile
  • Have bilirubin and gamma-glutamyl transpeptidase greater than 2 times the upper limit of normal at screening or Day -1
  • Be currently or within the past 30 days participating in any other research protocol involving investigational agents or therapies (Other than approved therapy)
  • Have received gene transfer agents within the past 6 months
  • Have any other concurrent condition that, in the opinion of the investigator, would make the subject unsuitable for the study.

Sites / Locations

  • University of Florida

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
March 24, 2022
Last Updated
August 21, 2023
Sponsor
University of Florida
Collaborators
University of Miami, University of Massachusetts, Worcester
search

1. Study Identification

Unique Protocol Identification Number
NCT05317780
Brief Title
Canavan-Single Patient IND
Official Title
Expanded Access Trial of Systemic Delivery of Aspartoacylase ASPA (rAAV9-CB6-AspA) Gene Vector in a Single Patient With Canavan Disease
Study Type
Expanded Access

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
No longer available
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Florida
Collaborators
University of Miami, University of Massachusetts, Worcester

4. Oversight

5. Study Description

Brief Summary
A recombinant virus vector constructed from adeno-associated virus (AAV) has been engineered to carry the human aspartoacylase (ASPA) gene expressed from a modified CMV-enhancer chicken β-actin (CB6) promoter. The construct has been shown to produce ASPA in animal models of Canavan disease, which closely match the proposed human study. The proposed clinical trial is an open label, expanded access study administering rAAV9-CB6-AspA gene vector by simultaneous systemic and intracerebroventricular routes to a single human subject (18-24 months of age) with Canavan disease. The subject will also receive immune modulation to transiently ablate B-cells (Rituximab) and modulate T-cell response (Sirolimus) prior to the initial exposure to AAV9. Given the null AspA mutations of the subject and current AAV seronegative status, this regimen will allow for later exposure to the therapeutic vector if needed and block any immuno-toxicity in the CNS. The goal of this study is to measure the safety and efficacy of AAV-mediated gene therapy as a treatment approach for neuronal pathology in Canavan disease. The subject will act as their own control and change from baseline will be assessed in regards to levels of brain NAA, brain water content and morphology, improved clinical status and peripheral levels of NAA. Safety parameters measured in this study will include: serum chemistries and hematology, urinalysis, physical assessments, whole blood assay for vector genomes, immunologic response to ASPA and AAV, as well as reported subject symptom history.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Canavan Disease
Keywords
Gene Therapy

7. Study Design

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
rAAV9-CB6-AspA
Intervention Description
This study is an open label, expanded access trial of a simultaneous, single intravenous (IV) and intracerebroventricular (ICV) administration of rAAV9-CB6-AspA in a child with Canavan disease. The subject will also receive an immunosuppression protocol to prevent reaction to ASPA and vector capsids.

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
This is a single patient IND, the patient was previously identified.
Minimum Age & Unit of Time
18 Months
Maximum Age & Unit of Time
24 Months
Eligibility Criteria
Inclusion Criteria: Male 18-24 months of age at time of study enrollment Have a diagnosis of Canavan disease, as defined by biochemical criteria AND/OR genetic mutation analysis, AND demonstrate clinical findings such as macrocephaly, developmental delay, seizures or other positive findings Elevated brain NAA levels, which is correlated with NAA acidemia and aciduria Willing to discontinue aspirin, aspirin-containing products and other drugs that may alter platelet function 7 days prior to dosing, resuming 24 hours after the gene transfer agent has been administered Exclusion Criteria: Have required acute (as distinguished from long-term, maintenance or chronic suppressive) oral or intravenous antibiotic therapy for a respiratory infection within 15 days prior to screening Have required oral or systemic corticosteroids within the last 15 days prior to baseline screening Have a platelet count less than 75,000/mm3 Have history of platelet dysfunction, evidence of abnormal platelet function at screening, or history of recent use of drugs that may alter platelet function, which the subject is unable/unwilling to discontinue for study agent administration Have an INR greater than 1.3 Have transaminases and alkaline phosphatase more than ten times the upper limit of normal at screening or Day-1; or an abnormal chemistry profile Have bilirubin and gamma-glutamyl transpeptidase greater than 2 times the upper limit of normal at screening or Day -1 Be currently or within the past 30 days participating in any other research protocol involving investigational agents or therapies (Other than approved therapy) Have received gene transfer agents within the past 6 months Have any other concurrent condition that, in the opinion of the investigator, would make the subject unsuitable for the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barry J Byrne, MD
Organizational Affiliation
University of Florida
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Canavan-Single Patient IND

We'll reach out to this number within 24 hrs