A Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study)

Taysha Gene Therapies

Status and phase: Enrolling; Phase 3

Conditions: Rett Syndrome

Treatments: Genetic: TSHA-102

Study type: Interventional

Funder types: Industry

Identifiers

NCT05606614

TSHA-102-CL-101

Details and patient eligibility

About

The primary objectives of this study are to evaluate the safety of a single intrathecal (IT) dose of TSHA-102 in females with typical Rett syndrome, to select the TSHA-102 dose with the best benefit/risk profile based on the totality of safety and efficacy data and to evaluate the efficacy and safety of TSHA-102 at the selected dose.

Full description

REVEAL Part A (Phase 1/2) is an open-label safety and dose-finding study designed to evaluate the safety and preliminary efficacy of two dose levels of TSHA-102 to establish initial safety of TSHA-102 and select a safe and efficacious dose for further evaluation. Enrollment of 6 participants in Part A is complete.

REVEAL Part B (Phase 3) will evaluate the efficacy and safety of TSHA-102 at the dose level 2 determined in Part A in 15 females ages 6 to <22 years 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 in Part A and B.

Enrollment: 15 estimated patients

Sex: Female

Ages: 6 to 21 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Females between the ages of 12 and <22 in Part A (closed) and females between the ages of 6 and <22 in Part B (pivotal cohort).
• 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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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15 participants in 3 patient groups

Part A Cohort 1

Experimental group

Description:

TSHA-102 Dose Level 1: 5.7×10¹⁴ total vector genomes (vg). Participants receive a single intrathecal (IT) administration of TSHA-102 at Dose Level 1 (fully enrolled, 2 participants).

Treatment:

Genetic: TSHA-102

Part A Cohort 2

Experimental group

Description:

TSHA-102 Dose Level 2: 1.0×10¹⁵ total vector genomes (vg) Participants receive a single intrathecal (IT) administration of TSHA-102 at Dose Level 2 (fully enrolled, 4 participants).

Treatment:

Genetic: TSHA-102

Part B Pivotal Cohort

Experimental group

Description:

TSHA-102 at Selected Dose (Dose Level 2): 1.0 × 10¹⁵ total vector genomes (vg) Participants receive a single intrathecal (IT) administration of TSHA-102 at Dose Level 2 (1.0 × 10¹⁵).

Treatment:

Genetic: TSHA-102