Canavan DiseaseNCT05317780
Canavan-Single Patient IND
A study testing rAAV9-CB6-AspA in people with Canavan Disease, run by University of Florida at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 24 months, men only
- Conditions the study is for
- Canavan Disease
- What is being tested?
- rAAV9-CB6-AspA
- Type of treatment
- Injection or infusion
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Expanded access
- 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 18 to 24 months
- Men only
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Expanded Access Trial of Systemic Delivery of Aspartoacylase ASPA (rAAV9-CB6-AspA) Gene Vector in a Single Patient With Canavan Disease
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.
- Conditions
- Canavan Disease
- Being tested
- rAAV9-CB6-AspA
- Keywords
- Gene Therapy
- Medical subject headings
- Canavan Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV9-CB6-AspADrug
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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Canavan DiseaseStudies of the same condition, open and under way.
- More trials run by University of FloridaThe 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
- Expanded access
Sponsor and investigators
- Lead sponsor
- University of Florida
- Sponsor type
- University, hospital or other
- Collaborators
- University of Miami, University of Massachusetts, Worcester
- Responsible party
- Sponsor
- Investigators
- Barry J Byrne, MD, Principal investigator, University of Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05317780
- Sponsor's protocol ID
- 201601620
- Status last verified
- Aug 2023
- First submitted
- 24 Mar 2022
- Last updated
- 23 Aug 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Expanded Access Trial of Systemic Delivery of Aspartoacylase ASPA (rAAV9-CB6-AspA) Gene Vector in a Single Patient With Canavan Disease
- ClinicalTrials.gov ID
- NCT05317780
- Acronym / sponsor ID
- 201601620
- Conditions
- Canavan Disease
- Keywords
- Gene Therapy
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- University of FloridaUniversity, hospital or other
- Collaborators
- University of Miami, University of Massachusetts, Worcester
- First posted
- 8 Apr 2022 (actual)
- 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.
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.
Study design
Who may qualify
- Ages
- 18 to 24 months
- Sex
- Male only
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| rAAV9-CB6-AspAThis 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. | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2023.
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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.
Barry J Byrne, MD principal investigator
University of Florida
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing rAAV9-CB6-AspA in people with Canavan Disease, run by University of Florida at 1 site in United States.
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 5 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 23 Aug 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 United States. 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.
Are results available for this study?
Results are not available in the source record.
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.
Where can I read the original study information?
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 23 Aug 2023.