Rett SyndromePhase 3NCT05606614
A Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study)
A Phase 3 study testing TSHA-102 in people with Rett Syndrome, run by Taysha Gene Therapies, Inc. at 9 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 6 to 21 years, women only
- Conditions the study is for
- Rett Syndrome
- What is being tested?
- TSHA-102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 9 sitesin 2 countries
- Study dates
- 6 Mar 2023to Jun 2031
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 21 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
9 sites in 2 countries.
9 sites in 2 countries
United States8 sites
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Boston Children's Hospital
Boston, Massachusetts, 02115
Rush University Medical Center
Chicago, Illinois, 60612
UT Southwestern Children's Medical Center
Dallas, Texas, 75930
City of Hope
Duarte, California, 91010
UC San Diego
La Jolla, California, 92093
UC San Francisco Benioff Children's Hospital
Oakland, California, 94609
Washington University, St. Louis
St Louis, Missouri, 63110
About this study
Official title: An Open-label Phase 1/2/3 Study Consisting of a Phase 1/2 Safety and Dose-escalation and Phase 3 Dose-expansion Study to Evaluate Safety and Efficacy of a Single Intrathecal Administration of TSHA-102, an AAV9-Delivered Gene Therapy in Females With Rett Syndrome
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.
- Conditions
- Rett Syndrome
- Being tested
- TSHA-102
- 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
- Medical subject headings
- Rett Syndrome, Neurodevelopmental Disorders, Genetic Diseases, X-Linked, Nervous System Diseases, Neurologic Manifestations, Intellectual Disability, Pathologic Processes, X-Linked Intellectual Disability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TSHA-102Genetic
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.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: 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) (fully enrolled, 17 participants). Receives: Genetic: TSHA-102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Part A: Safety and Tolerability of TSHA-102
Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
Measured: 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.
Measured: Baseline through Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2022
- Study start6 Mar 2023
- Primary completionJun 2031 (estimated)
- Study completionJun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Rett SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- The study treatment will be delivered via intrathecal (IT) injection.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Taysha Gene Therapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Monitor, M.D., Study director, Taysha Gene Therapies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05606614
- Sponsor's protocol ID
- TSHA-102-CL-101
- Status last verified
- Jul 2026
- First submitted
- 28 Oct 2022
- Last updated
- 7 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 38723617Sadhu 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
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Phase 1/2/3 Study Consisting of a Phase 1/2 Safety and Dose-escalation and Phase 3 Dose-expansion Study to Evaluate Safety and Efficacy of a Single Intrathecal Administration of TSHA-102, an AAV9-Delivered Gene Therapy in Females With Rett Syndrome
- ClinicalTrials.gov ID
- NCT05606614
- Acronym / sponsor ID
- TSHA-102-CL-101
- Conditions
- Rett Syndrome
- Keywords
- Rett Syndrome, Neurodevelopmental disorder, Rett, MECP2, AAV9, Typical Rett Syndrome, Classic Rett Syndrome, RTT
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Taysha Gene Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- 6 Mar 2023 (actual)
- Primary completion
- Jun 2031 (estimated)
- Study completion
- Jun 2031 (estimated)
- First posted
- 7 Nov 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 3
- Model description
- The study treatment will be delivered via intrathecal (IT) injection.
| Arm | Type | Receives |
|---|---|---|
| Part A Cohort 1 | Experimental | Genetic: TSHA-102TSHA-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). |
| Part A Cohort 2 | Experimental | Genetic: TSHA-102TSHA-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). |
| Part B Pivotal Cohort | Experimental | Genetic: TSHA-102TSHA-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). |
Who may qualify
- Ages
- 6 to 21 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TSHA-102TSHA-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. | Genetic | Part A Cohort 1, Part A Cohort 2, Part B Pivotal Cohort |
Primary outcome
Part A: Safety and Tolerability of TSHA-102
Time frame: Baseline through Week 52
Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
Part B: Efficacy of TSHA-102
Time frame: Baseline through Week 52
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2026.
- Derived from this study: PubMed 38723617Jagadeeswaran 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.
- Derived from this study: PubMed 38254921Sadhu 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Monitor, M.D. study director
Taysha Gene Therapies
9 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing TSHA-102 in people with Rett Syndrome, run by Taysha Gene Therapies, Inc. at 9 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 7 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part A: Safety and Tolerability of TSHA-102 (time frame: Baseline through Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05606614, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2026.