Rett Syndrome
Conditions
Keywords
Neurodevelopmental Disorders, Rett, MECP2, AAV9, Typical Rett Syndrome, Classic Rett Syndrome, RTT, Rett Disorder, Retts, MECP2-Related Disorder, Gene Therapy, Intrathecal Administration, Genetic Diseases, X-Linked, Nervous System Diseases, Developmental Regression, TSHA-102, miRARE, Self-complementary Vector, Neurologic Manifestations, Intellectual Disability, Pathologic Process, X-Linked Intellectual Disability, Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Brief summary
The primary objectives of this study are to evaluate the safety, tolerability and preliminary efficacy of a single intrathecal (IT) dose of TSHA-102 in pediatric females with typical Rett syndrome.
Detailed description
ASPIRE is an open-label study designed to evaluate the safety, tolerability and preliminary efficacy of TSHA-102 in 3 pediatric females aged 2 to less than 4 years old with typical Rett syndrome. TSHA-102 is designed to target the genetic root cause of Rett syndrome by regulating the expression of MECP2 in cells. Each participant will be followed for the observation period of 5 years after TSHA-102 administration.
Interventions
GENETICTSHA-102
TSHA-102 is a recombinant, non-replicating, self-complementary adeno-associated virus serotype 9 (scAAV9) vector encoding for the miniMECP2 gene. TSHA-102 is a one-time intrathecal (IT) administration.
Sponsors
Taysha Gene Therapies, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Blinded central raters
Intervention model description
Participants will receive a single dose of TSHA-102 at a dose level of 1.0×10¹⁵ total vector genomes (vg) adjusted for the participant's brain volume. TSHA-102 will be administered via lumbar puncture (LP). The study comprises a screening period, TSHA-102 administration, a primary safety analysis period through 25 weeks post TSHA-102 administration, and an extended follow-up observation period through 5 years post TSHA-102 administration.
Eligibility
Sex/Gender
FEMALE
Age
2 Years to 3 Years
Healthy volunteers
No
Inclusion criteria
* Pediatric females between the ages of 2 and less than 4 years old. * Participant has a clinical diagnosis of classic/typical Rett syndrome with a documented pathogenic mutation of the methyl-CpG-binding protein 2 (MECP2) gene that results in loss of gene function. * Participants must be willing to receive blood or blood products for the treatment of an AE if medically needed. * Participants and parent/caregiver must agree to reside within easy access to the study site prior to the baseline visit and at least 3 months after TSHA-102 treatment.
Exclusion criteria
* Participant has another neurodevelopmental disorder independent of the MECP2 loss-of-function mutation, or any other genetic syndrome with a progressive course. * Participant has a history of brain injury that causes neurological problems or had grossly abnormal psychomotor development in the first 6 months of life. * Participant has a diagnosis of atypical Rett syndrome or a MECP2 gene mutation that does not cause Rett syndrome. * Participant requires invasive ventilatory support. Note: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety | Baseline through Week 25 | Safety and Tolerability of TSHA-102 Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs) |
Countries
United States
Contacts
STUDY_DIRECTORMedical Monitor, M.D.
Taysha Gene Therapies
Outcome results
None listed