Canavan DiseasePhase 1/2CAN-GTNCT04833907
rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease
A Phase 1/2 study testing rAAV-Olig001-ASPA, Levetiracetam and Prednisone in people with Canavan Disease, run by Myrtelle Inc. at 1 site in United States.
Trial summary
Canavan Disease is a congenital white matter disorder caused by mutations to the gene encoding for aspartoacylase (ASPA). Expression of ASPA is restricted to oligodendrocytes, the sole white matter producing lineage in the brain. Read more about this study
- Who is it for?
- Ages 3 to 60 months
- Conditions the study is for
- Canavan Disease
- What is being tested?
- rAAV-Olig001-ASPA, Levetiracetam and Prednisone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2021to 31 Aug 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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 3 to 60 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Definitive diagnosis of typical CD by a board certified neurologist.
- Written informed consent from parent(s)/guardian(s). Consent to enroll into the study will include a written agreement to comply with all the conditions of the study, including attendance at follow-up visits.
- For cohort 1: age more than 36 months and up to 60 months.
- For cohort 2: age between 15 months and 36 months.
- For cohort 3: age less than 15 months.
Who cannot join
- At the discretion of the PI, any significant chronic medical condition, including, but not limited to neurological, cardiac, hepatic, renal, hematological, gastrointestinal, endocrine, pulmonary, or infectious disease, which would put the subject at increased risk during surgery or which would interfere with participation in the study, interpretation of safety monitoring, or the integrity of the study data.
- History of severe allergic reaction or anaphylaxis.
- Past participation in gene therapy trials or receipt of any other investigational product within 6 months prior to enrollment.
- Prior intracranial surgery.
- Any absolute contraindication to immunosuppression.
- Any absolute contraindication to MRI.
Show all 10Show fewer
- Any vaccination less than 1 month prior to gene therapy.
- Anticipated life expectancy of less than 12 months for any reason.
- GMFM-88 total raw score >35%.
- Clinically significant out-of-range lab values, at the discretion of clinical PI.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Phase 1/2, Open Label, Sequential Cohort Study of a Single Intracranial Dose of AVASPA Gene Therapy for Treatment of Children With Typical Canavan Disease
Canavan Disease is a congenital white matter disorder caused by mutations to the gene encoding for aspartoacylase (ASPA). Expression of ASPA is restricted to oligodendrocytes, the sole white matter producing lineage in the brain. ASPA supports myelination in the capacity of its sole known function, namely, the catabolism of N-acetylaspartate (NAA). Inherited mutations that result in loss of ASPA catabolic activity result in a typically severe phenotype of Canavan Disease, characterized by chronically elevated brain NAA, gross motor abnormalities, hypomyelination, progressive spongiform degeneration of the brain, epilepsy, blindness, and a short life expectancy. Disease severity is correlated with residual levels of enzyme activity. Reconstitution of ASPA function in oligodendrocytes of the brains of Canavan patients is expected to rescue NAA metabolism in its natural cellular compartment and support myelination/remyelination by resident white matter producing cells. This protocol directly targets oligodendrocytes in the brain, which are intimately involved with disease initiation and progression. Targeting oligodendrocytes offers the safest and most direct therapy for affected individuals.
The latest generation AAV viral vector (rAAV-Olig001-ASPA) will be administered to patients using neurosurgical procedure which involves direct administration of gene therapy to affected regions of the brain. Outcome measures for the open label clinical trial include longitudinal clinical assessments and brain imaging.
Read more
Currently, there is no effective treatment for Canavan Disease. The purpose of this study is to validate a new technology targeted to the cells most affected by Canavan Disease in the safest way possible.
The study investigators are committed to supporting the Rare Disease \& Canavan Disease Communities. For more information, please contact Jordana Holovach, Head of Communications and Community at PatientAdvocacy@myrtellegtx.com.
Read the detailed description
rAAV-Olig001-ASPA is the first gene therapy designed to target the oligodendrocytes, which are critical for myelination and brain development.
This study is a Phase 1/2 First-In-Human protocol designed to obtain safety, pharmacodynamics, and efficacy data following neurosurgical administration of a single dose of rAAV-Olig001-ASPA delivered intracerebroventricularly in up to 24 children with Canavan Disease.
Patients with a diagnosis of typical Canavan Disease who meet all eligibility criteria may be enrolled in this open-label, sequential cohort study of a single dose of rAAV-Olig001-ASPA.
- Conditions
- Canavan Disease
- Being tested
- rAAV-Olig001-ASPA, Levetiracetam, Prednisone
- Keywords
- Canavan Disease, Gene Therapy, Aspartoacylase, N-Acetyl-Aspartate, Oligodendrocyte, Leukodystrophy, Adeno-Associated Virus Vector, Autosomal Recessive Disorder, Neurodegenerative, White Matter Disorder
- Medical subject headings
- Canavan Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rAAV-Olig001-ASPADrug
Also called MYR-101
Intracerebroventricular administration of a single dose
LevetiracetamDrug
Also called Keppra
Keppra daily dose (20-50 mg/kg/day divided twice daily administered orally or per G-tube) in the post-operative period and continued for 3 months per standard of care to prevent seizure activity.
PrednisoneDrug
Post-operatively, a 3-month steroid taper is planned to prevent or reduce possible delayed immunological responses. This tapering regimen will consist of 0.5 mg/kg/day prednisone during weeks 1-4; followed by 0.3 mg/kg/day prednisone during weeks 5-8; and 0.1mg prednisone during weeks 9-12, then off. If there is evidence of new inflammation on MRI at 3-months on T2 FLAIR, the steroid taper will be extended for an additional 3 months or we will transition to steroid-sparing immunosuppression.
| Study group | Role | What they receive |
|---|---|---|
| 3.7 x 10^13 v.g. rAAV-Olig001-ASPA | Experimental | 3.7 x 10^13 v.g. of rAAV-Olig001-ASPA administered as a single dose neurosurgically to the brain via 2 pre-defined intracerebroventricular sites Receives: Drug: rAAV-Olig001-ASPA; Drug: Levetiracetam; Drug: Prednisone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety evaluation
Number, severity, and causal relationship of any adverse event (to either the gene therapy and/or surgical trial procedures required for vector administration) using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measured: 12 Months Post Dose
Secondary outcomes (7)
Myelination
Change from baseline measured by cerebral Synthetic Magnetic Resonance Imaging (SyMRI)
Measured: 12 Months Post Dose
N-Acetyl-Aspartate (NAA) concentrations in the Brain
N-Acetyl-Aspartate concentrations will be assessed with nuclear Magnetic Resonance Spectroscopy (nMRS) between pre- and post-treatment and as compared to historical controls.
Measured: 12 Months Post Dose
Neurological Evaluation - Motor Function
Motor Function will be analyzed using the Gross Motor Function Measure (GMFM)-88 scale for motor function assessment before and after vector administration and compared to historical controls. The GMFM consists of 5 scales: Lying and Rolling, Sitting, Crawling and Kneeling, Standing and Walking, Running and Jumping. The total scores range from 0 to 264. The lower the score on GMFM, the weaker the ability; the higher the score, the greater the ability.
Measured: 12 Months Post Dose
Neurological Evaluation - Neurocognitive Function
Neurocognitive function will be assessed using the Mullen Scales of Early Learning (MSEL) before and after vector administration and compared to historical controls. The MSEL is a cognitive test to measure cognitive ability and language development. The MSEL test has five scales: Gross motor, Visual reception, Fine motor, Receptive language, and Expressive language. The total scores range from 0 to 197. The lower the score on MSEL, the weaker the ability; the higher the score, the greater the ability.
Measured: 12 Months Post Dose
Neurological Evaluation - Spasticity
Will be assessed using the Canavan Neurological Evaluation before and after vector administration and compared to historical controls.
Measured: 12 Months Post Dose
Seizure Assessment
Will be assessed based on reported seizure activity and Electroencephalograms alpha, beta, delta, and theta wave frequencies (Hz).
Measured: 12 Months Post Dose
NAA concentration measured in Cerebrospinal Fluid (CSF)
CSF will be collected via lumbar puncture and analyzed to assess concentrations of N-Acetyl-Aspartate.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2021
- Study start1 Apr 2021
- Primary completion31 Aug 2026 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Canavan DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Myrtelle Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Lober, MD, PhD, Principal investigator, Dayton Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04833907
- Sponsor's protocol ID
- CAN-GT
- Acronym
- CAN-GT
- Status last verified
- Jan 2025
- First submitted
- 24 Mar 2021
- Last updated
- 14 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Francis JS, Markov V, Wojtas ID, Gray S, McCown T, Samulski RJ, Figueroa M, Leone P. Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease. Mol Ther Methods Clin Dev. 2021 Jan 21;20:520-534. doi: 10.1016/j.omtm.2021.01.009. eCollection 2021 Mar 12.
PubMed 33614826Francis JS, Wojtas I, Markov V, Gray SJ, McCown TJ, Samulski RJ, Bilaniuk LT, Wang DJ, De Vivo DC, Janson CG, Leone P. N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase. Neurobiol Dis. 2016 Dec;96:323-334. doi: 10.1016/j.nbd.2016.10.001. Epub 2016 Oct 4.
PubMed 27717881Leone P, Lober RM, Francis J, Flamini O, Cecil KM, Shera D, Janson CG. Oligodendrocyte-targeted adeno-associated virus gene therapy for Canavan disease in children: a phase 1/2 trial. Nat Med. 2025 Nov;31(11):3772-3779. doi: 10.1038/s41591-025-03919-w. Epub 2025 Sep 16.
PubMed 40957959
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/2, Open Label, Sequential Cohort Study of a Single Intracranial Dose of AVASPA Gene Therapy for Treatment of Children With Typical Canavan Disease
- ClinicalTrials.gov ID
- NCT04833907
- Acronym / sponsor ID
- CAN-GT / CAN-GT
- Conditions
- Canavan Disease
- Keywords
- Canavan Disease, Gene Therapy, Aspartoacylase, N-Acetyl-Aspartate, Oligodendrocyte, Leukodystrophy, Adeno-Associated Virus Vector, Autosomal Recessive Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Enrolling by invitation
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Myrtelle Inc.Industry (pharma, biotech, devices)
- Study start
- 1 Apr 2021 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 6 Apr 2021 (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.
Canavan Disease is a congenital white matter disorder caused by mutations to the gene encoding for aspartoacylase (ASPA). Expression of ASPA is restricted to oligodendrocytes, the sole white matter producing lineage in the brain. ASPA supports myelination in the capacity of its sole known function, namely, the catabolism of N-acetylaspartate (NAA). Inherited mutations that result in loss of ASPA catabolic activity result in a typically severe phenotype of Canavan Disease, characterized by chronically elevated brain NAA, gross motor abnormalities, hypomyelination, progressive spongiform degeneration of the brain, epilepsy, blindness, and a short life expectancy. Disease severity is correlated with residual levels of enzyme activity. Reconstitution of ASPA function in oligodendrocytes of the brains of Canavan patients is expected to rescue NAA metabolism in its natural cellular compartment and support myelination/remyelination by resident white matter producing cells. This protocol directly targets oligodendrocytes in the brain, which are intimately involved with disease initiation and progression. Targeting oligodendrocytes offers the safest and most direct therapy for affected individuals.
The latest generation AAV viral vector (rAAV-Olig001-ASPA) will be administered to patients using neurosurgical procedure which involves direct administration of gene therapy to affected regions of the brain. Outcome measures for the open label clinical trial include longitudinal clinical assessments and brain imaging.
Currently, there is no effective treatment for Canavan Disease. The purpose of this study is to validate a new technology targeted to the cells most affected by Canavan Disease in the safest way possible.
The study investigators are committed to supporting the Rare Disease \& Canavan Disease Communities. For more information, please contact Jordana Holovach, Head of Communications and Community at PatientAdvocacy@myrtellegtx.com.
Detailed description
rAAV-Olig001-ASPA is the first gene therapy designed to target the oligodendrocytes, which are critical for myelination and brain development.
This study is a Phase 1/2 First-In-Human protocol designed to obtain safety, pharmacodynamics, and efficacy data following neurosurgical administration of a single dose of rAAV-Olig001-ASPA delivered intracerebroventricularly in up to 24 children with Canavan Disease.
Patients with a diagnosis of typical Canavan Disease who meet all eligibility criteria may be enrolled in this open-label, sequential cohort study of a single dose of rAAV-Olig001-ASPA.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 3.7 x 10^13 v.g. rAAV-Olig001-ASPA | Experimental | Drug: rAAV-Olig001-ASPA, Drug: Levetiracetam, Drug: Prednisone3.7 x 10^13 v.g. of rAAV-Olig001-ASPA administered as a single dose neurosurgically to the brain via 2 pre-defined intracerebroventricular sites |
Who may qualify
- Ages
- 3 to 60 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Definitive diagnosis of typical CD by a board certified neurologist.
- Written informed consent from parent(s)/guardian(s). Consent to enroll into the study will include a written agreement to comply with all the conditions of the study, including attendance at follow-up visits.
- For cohort 1: age more than 36 months and up to 60 months.
- For cohort 2: age between 15 months and 36 months.
- For cohort 3: age less than 15 months.
Key exclusion criteria (10 listed)
- At the discretion of the PI, any significant chronic medical condition, including, but not limited to neurological, cardiac, hepatic, renal, hematological, gastrointestinal, endocrine, pulmonary, or infectious disease, which would put the subject at increased risk during surgery or which would interfere with participation in the study, interpretation of safety monitoring, or the integrity of the study data.
- History of severe allergic reaction or anaphylaxis.
- Past participation in gene therapy trials or receipt of any other investigational product within 6 months prior to enrollment.
- Prior intracranial surgery.
- Any absolute contraindication to immunosuppression.
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 |
|---|---|---|
| rAAV-Olig001-ASPAAlso: MYR-101Intracerebroventricular administration of a single dose | Drug | 3.7 x 10^13 v.g. rAAV-Olig001-ASPA |
| LevetiracetamAlso: KeppraKeppra daily dose (20-50 mg/kg/day divided twice daily administered orally or per G-tube) in the post-operative period and continued for 3 months per standard of care to prevent seizure activity. | Drug | 3.7 x 10^13 v.g. rAAV-Olig001-ASPA |
| PrednisonePost-operatively, a 3-month steroid taper is planned to prevent or reduce possible delayed immunological responses. This tapering regimen will consist of 0.5 mg/kg/day prednisone during weeks 1-4; followed by 0.3 mg/kg/day prednisone during weeks 5-8; and 0.1mg prednisone during weeks 9-12, then off. If there is evidence of new inflammation on MRI at 3-months on T2 FLAIR, the steroid taper will be extended for an additional 3 months or we will transition to steroid-sparing immunosuppression. | Drug | 3.7 x 10^13 v.g. rAAV-Olig001-ASPA |
Primary outcome
Safety evaluation
Time frame: 12 Months Post Dose
Number, severity, and causal relationship of any adverse event (to either the gene therapy and/or surgical trial procedures required for vector administration) using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
7 secondary outcomes
Myelination
Time frame: 12 Months Post Dose
N-Acetyl-Aspartate (NAA) concentrations in the Brain
Time frame: 12 Months Post Dose
Neurological Evaluation - Motor Function
Time frame: 12 Months Post Dose
Neurological Evaluation - Neurocognitive Function
Time frame: 12 Months Post Dose
Neurological Evaluation - Spasticity
Time frame: 12 Months Post Dose
Seizure Assessment
Time frame: 12 Months Post Dose
NAA concentration measured in Cerebrospinal Fluid (CSF)
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Nov 2025.
- Background: PubMed 33614826Francis JS, Markov V, Wojtas ID, Gray S, McCown T, Samulski RJ, Figueroa M, Leone P. Preclinical biodistribution, tropism, and efficacy of oligotropic AAV/Olig001 in a mouse model of congenital white matter disease. Mol Ther Methods Clin Dev. 2021 Jan 21;20:520-534. doi: 10.1016/j.omtm.2021.01.009. eCollection 2021 Mar 12.
- Background: PubMed 27717881Francis JS, Wojtas I, Markov V, Gray SJ, McCown TJ, Samulski RJ, Bilaniuk LT, Wang DJ, De Vivo DC, Janson CG, Leone P. N-acetylaspartate supports the energetic demands of developmental myelination via oligodendroglial aspartoacylase. Neurobiol Dis. 2016 Dec;96:323-334. doi: 10.1016/j.nbd.2016.10.001. Epub 2016 Oct 4.
- Derived from this study: PubMed 40957959Leone P, Lober RM, Francis J, Flamini O, Cecil KM, Shera D, Janson CG. Oligodendrocyte-targeted adeno-associated virus gene therapy for Canavan disease in children: a phase 1/2 trial. Nat Med. 2025 Nov;31(11):3772-3779. doi: 10.1038/s41591-025-03919-w. Epub 2025 Sep 16.
- Canavan Disease ResearchLink provided by the sponsor.
- Canavan Disease Advocacy, Research, Patient assistance, EducationLink provided by the sponsor.
- Canavan Disease Advocacy, Research, Patient assistance, EducationLink provided by the sponsor.
- Canavan Disease Advocacy, Research, Patient assistance, EducationLink provided by the sponsor.
- Canavan Disease Advocacy, Research, Patient assistance, EducationLink provided by the sponsor.
- Canavan Disease Advocacy, Research, Patient assistance, EducationLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Canavan Disease
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
RecruitingPhase 1/2
A Study of AAV9 Gene Therapy in Participants With Canavan Disease (CANaspire Clinical Trial)
Canavan Disease
RecruitingObservational study
The Myelin Disorders Biorepository Project
Leukodystrophy, White Matter Disease
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.
Robert Lober, MD, PhD principal investigator
Dayton Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing rAAV-Olig001-ASPA, Levetiracetam and Prednisone in people with Canavan Disease, run by Myrtelle Inc. 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: enrolling by invitation, as of the sponsor's last update on 14 Nov 2025. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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.
What does the primary outcome measure?
Safety evaluation (time frame: 12 Months Post Dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04833907, which also lists 3 linked publications.
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 14 Nov 2025.