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

NCT07480564 — Phase 3, Active not recruiting, 4 participants, Taysha Gene Therapies, Inc.

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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

Registry	NCT07480564, acronym ASPIRE
Status	Active not recruiting
Phase	Phase 3
Study type	Interventional; na, single group, masking: none, treatment
Enrollment	4 (Actual)
Sponsor	Taysha Gene Therapies, Inc. (Industry)
Conditions	Rett Syndrome
Interventions	TSHA-102 (Genetic)
Dates	start 2026-05-08, primary completion 2031-06-01 (estimated), completion 2031-06-01 (estimated), first posted 2026-03-18, last updated 2026-08-19
Locations	3 sites in United States

-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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
Treatment	Experimental	Genetic: TSHA-102	Participants receive a single intrathecal (IT) administration of TSHA-102 at 1.0 × 10¹⁵ total vector genomes (vg) adjusted for the participant's brain volume.

TSHA-102 (Genetic): 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.

+Outcome measures

Primary outcomes

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)

+Eligibility

Sex: Female, ages: 2 Years to 3 Years

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

+Locations (3)

Facility	City	Country
University of Alabama at Birmingham	Birmingham, Alabama	United States
Rush University Medical Center	Chicago, Illinois	United States
Boston Children's Hospital	Boston, Massachusetts	United States

+Investigators

Medical Monitor, M.D., Study director, Taysha Gene Therapies