rAAV-Olig001-ASPA Gene Therapy for Treatment of Children With Typical Canavan Disease

Part of paid clinical trials in Dayton, Ohio.

Sponsor
Myrtelle Inc.
Study ID
NCT04833907
Phase
PHASE1/PHASE2
Status
Enrolling By Invitation

Conditions

  • Canavan Disease

Eligibility Criteria

Sex
ALL
Age
3 Months - 60 Months
Healthy Volunteers
Not accepted

Interventions

  • rAAV-Olig001-ASPA — DRUG
    Intracerebroventricular administration of a single dose
  • Levetiracetam — DRUG
    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.
  • Prednisone — DRUG
    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 Details

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 [email protected].

Key Dates

Start date
Apr 1, 2021
Status verified
Jan 2025
Primary completion
Aug 31, 2026
Completion
Aug 31, 2027

Study Design

Enrollment
24 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: 3.7 x 10^13 v.g. rAAV-Olig001-ASPA
    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

Primary Outcome Measure

Safety evaluation [ Time Frame: 12 Months Post Dose ]

Locations (1)

FacilityCityStateZIPSite coordinators
Dayton Children's HospitalDaytonOhio45404-

Find similar trials in Dayton, OH

By research site
Dayton Children's Hospital· Dayton, OH

Related Studies