MedDataX Logo

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

NCT ID: NCT05606614

Last Updated: 2025-12-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-06

Study Completion Date

2031-06-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Rett Syndrome

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

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

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The study treatment will be delivered via intrathecal (IT) injection.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Central raters assessing the gain or regain of a developmental milestone from videos are blinded to the timing of each video.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Part A Cohort 1

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).

Group Type EXPERIMENTAL

TSHA-102

Intervention Type 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 2

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).

Group Type EXPERIMENTAL

TSHA-102

Intervention Type 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 B Pivotal Cohort

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).

Group Type EXPERIMENTAL

TSHA-102

Intervention Type 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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TSHA-102

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.

Intervention Type GENETIC

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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.
Minimum Eligible Age

6 Years

Maximum Eligible Age

21 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Taysha Gene Therapies, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Medical Monitor, M.D.

Role: STUDY_DIRECTOR

Taysha Gene Therapies

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

UC San Diego

La Jolla, California, United States

Site Status RECRUITING

Rush University Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University, St. Louis

St Louis, Missouri, United States

Site Status RECRUITING

UT Southwestern Children's Medical Center

Dallas, Texas, United States

Site Status RECRUITING

CHU St. Justine

Montreal, Quebec, Canada

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States Canada

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Taysha Gene Therapies Medical Information

Role: CONTACT

Phone: 833-489-8742

Email: [email protected]

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Karen Ditslear, M.S.

Role: primary

Milana Milic

Role: primary

Role: primary

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 38723617 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38254921 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

TSHA-102-CL-101

Identifier Type: -

Identifier Source: org_study_id