Safety and Preliminary Efficacy of TSHA-102 Gene Therapy in Pediatric Females Aged >2 to <4 Years With Rett Syndrome

ASPIRE Study: A Multicenter, Open-Label Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of a Single Intrathecal Administration of TSHA-102, an AAV9-Delivered Gene Therapy, for the Treatment of Pediatric Females Aged >2 to <4 Years With Rett Syndrome

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.

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.

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/exclusion criteria may apply