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Active, not recruitingNCT05606614Updated Jul 7, 2026

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

A Phase 3 interventional study of TSHA-102 in Rett Syndrome, sponsored by Taysha Gene Therapies, Inc.. Active, not recruiting at 9 sites in 2 countries. Open to female participants aged 6 Years to 21 Years. Per ClinicalTrials.gov, last updated 2026-07-07.

Sponsored by Taysha Gene Therapies, Inc. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
17
Allocation
Non-randomized
Ages
6 Years to 21 Years
Sex
Female
01

Study 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.

Read the detailed 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.

02

Conditions studied

  • 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
03

In context

Rett Syndrome

96 studies on the registry are indexed under Rett Syndrome; 19 are open to participants now.

This study's enrollment of 17 is below the median of 30 across 64 interventional studies indexed under Rett Syndrome.

Browse Rett Syndrome studies →

Lead sponsor

Taysha Gene Therapies, Inc. is the lead sponsor of 4 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years to 21 Years
Sexes eligible
Female
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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

05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
Single (Outcomes assessor)
Enrollment
17 participants (actual)

Study arms

  • Experimental
    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).

    Genetic: TSHA-102

  • Experimental
    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).

    Genetic: TSHA-102

  • Experimental
    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) (fully enrolled, 17 participants).

    Genetic: TSHA-102

Interventions

  • GeneticTSHA-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.

06

What researchers measure

Primary outcomes

  1. Part A: Safety and Tolerability of TSHA-102

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

    Time frame: Baseline through Week 52

  2. 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.

    Time frame: Baseline through Week 52

07

Study locations

9 sites
08

References and documents

Publications

  • 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. PubMed 38723617 ↗
  • 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. PubMed 38254921 ↗

Individual participant data

Plan to share: No

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Mar 2023 (actual). Primary completion is estimated for Jun 2031, 99 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 28, 2022
First posted
Nov 7, 2022
StartActual
Mar 6, 2023
Primary completionEst.
Jun 2031
CompletionEst.
Jun 2031
Last update
Jul 7, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 7, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05606614
Lead sponsor
Taysha Gene Therapies, Inc.
Responsible party
Sponsor
First posted
Nov 7, 2022
Start date
Mar 6, 2023
Primary completion
Jun 2031 (estimated)
Completion
Jun 2031 (estimated)
Last update
Jul 7, 2026

Study contacts

Medical Monitor, M.D.
study director · Taysha Gene Therapies

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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