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

NCT05606614 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: TSHA-102-CL-101
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 6

Brief Summary

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.

Conditions

Rett Syndrome

Keywords

Rett Syndrome; Neurodevelopmental disorder; 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

Outcome Measures

Primary Outcomes (2)

• Part A: Safety and Tolerability of TSHA-102

  Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)

  Baseline through Week 52

• Part B: Efficacy of TSHA-102

  Change from baseline in percentage of participants who gain or regain any one or more of the 28 items from the Developmental Milestones Assessment (DMA), which are video recorded and scored by independent, blinded central raters.

  Baseline through Week 52

Study Arms (3)

Part A Cohort 1

EXPERIMENTAL

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).

Genetic: TSHA-102

Part A Cohort 2

EXPERIMENTAL

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).

Genetic: TSHA-102

Part B Pivotal Cohort

EXPERIMENTAL

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).

Genetic: TSHA-102

Interventions

TSHA-102 GENETIC

TSHA-102 is a recombinant, non-replicating, self-complementary AAV9 (scAAV9) vector encoding for the miniMECP2 gene. TSHA-102 is a one-time intrathecal (IT) administration.

Part A Cohort 1; Part A Cohort 2; Part B Pivotal Cohort

Eligibility Criteria

• Age: 6 Years - 21 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Taysha Gene Therapies, Inc.: lead

Study Sites (6)

UC San Diego

La Jolla, California, 92093, United States

RECRUITING

Rush University Medical Center

Chicago, Illinois, 60612, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Washington University, St. Louis

St Louis, Missouri, 63110, United States

RECRUITING

UT Southwestern Children's Medical Center

Dallas, Texas, 75930, United States

RECRUITING

CHU St. Justine

Montreal, Quebec, Canada

RECRUITING

Related Publications (2)

• Jagadeeswaran I, Oh J, Sinnett SE. Preclinical Milestones in MECP2 Gene Transfer for Treating Rett Syndrome. Dev Neurosci. 2025;47(2):147-156. doi: 10.1159/000539267. Epub 2024 May 9.

  PMID: 38723617 DERIVED

• Sadhu C, Lyons C, Oh J, Jagadeeswaran I, Gray SJ, Sinnett SE. The Efficacy of a Human-Ready miniMECP2 Gene Therapy in a Pre-Clinical Model of Rett Syndrome. Genes (Basel). 2023 Dec 24;15(1):31. doi: 10.3390/genes15010031.

  PMID: 38254921 DERIVED

MeSH Terms

Conditions

Rett Syndrome; Neurodevelopmental Disorders; Genetic Diseases, X-Linked; Nervous System Diseases; Neurologic Manifestations; Intellectual Disability; Pathologic Processes; X-Linked Intellectual Disability; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Condition Hierarchy (Ancestors)

Neurobehavioral Manifestations; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Mental Disorders; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Medical Monitor, M.D.

  Taysha Gene Therapies

  STUDY DIRECTOR

Central Study Contacts

Taysha Gene Therapies Medical Information

CONTACT

833-489-8742; medinfo@tayshagtx.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Central raters assessing the gain or regain of a developmental milestone from videos are blinded to the timing of each video.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The study treatment will be delivered via intrathecal (IT) injection.

Study Record Dates

• First Submitted: October 28, 2022
• First Posted: November 7, 2022
• Study Start: March 6, 2023
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); CA (1)