Safety and Efficacy of TSHA-102 in Pediatric Females With Rett Syndrome (REVEAL Pediatric Study)

Rett Syndrome Clinical Trial

Official title:

A Multicenter, Open Label, Randomized, Dose-Escalation and Dose-Expansion Study of the Safety, Tolerability, and Efficacy of a Single Intrathecal Administration of TSHA-102, an AAV9-Delivered Gene Therapy, for the Treatment of Pediatric Females With Rett Syndrome

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06152237
• Other study ID #: TSHA-102-CL-102
• Status: Recruiting
• Phase: Phase 1
• Start date: December 12, 2023
• Est. completion date: November 2, 2031

Study information

• Verified date: February 2024
• Source: Taysha Gene Therapies, Inc.
• Contact: Taysha Gene Therapies Medical Information
• Phone: 1-833-489-8742
• Email: medinfo[@]tayshagtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The REVEAL Pediatric Study is a multi-center, Phase 1/2 open-label, dose-escalation and dose-expansion study of TSHA-102, an investigational gene therapy, in pediatric females with Rett Syndrome.

The safety, tolerability, and preliminary efficacy of two dose levels will be evaluated. The study duration is up to 6 years.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: November 2, 2031
• Est. primary completion date: November 2, 2028
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 5 Years to 8 Years

Eligibility

Inclusion Criteria:

• Participant has a confirmed diagnosis of classical/typical Rett Syndrome with a documented mutation of the MECP2 gene that results in loss of function.

• Participant is between =5 to =8 years of age at the time of consent.

• Participant must be up to date with all relevant local vaccination requirements, with last vaccination dose received at least 42 days prior to the start of the immunosuppression regimen.

• Participant's parent/caregiver must be willing to allow participant to receive blood or blood products for the treatment of an AE if medically needed.

Exclusion Criteria:

• Participant has another neurodevelopmental disorder independent of the MECP2 gene loss of function mutation, or any other genetic syndrome with a progressive course.

• Participant has a history of brain injury that causes neurological problems.

• Participant had grossly abnormal psychomotor development in the first 6 months of life.

• Participant has a diagnosis of atypical Rett syndrome.

• Participant has an MECP2 mutation that does not cause Rett syndrome.

• Participant requires non-invasive and invasive ventilatory support.

• Participant has contraindications for IT administration of TSHA-102 or lumbar puncture procedure, other medical conditions, or contraindications to any medications required for IT administration.

• Participant has acute or chronic hepatitis B or C infections.

Related Conditions & MeSH terms

• Rett Syndrome
• Syndrome

Intervention

Genetic:
• 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.

Locations

Country	Name	City	State
United Kingdom	Children's Neurosciences, Evelina London Children's Hospital, Guy's and St Thomas' NHS Foundation Trust	London
United States	Boston Children's at Brookline	Boston	Massachusetts
United States	Rush University Medical Center	Chicago	Illinois
United States	University of Texas Southwestern Medical Center (UTSW)	Dallas	Texas
United States	University of California San Diego (UCSD)	La Jolla	California
United States	Vanderbilt Kennedy Center	Nashville	Tennessee
United States	Children's Hospital of Philadelphia Research Institute	Philadelphia	Pennsylvania
United States	Washington University, St. Louis	Saint Louis	Missouri
United States	Gillette Children's Specialty Healthcare	Saint Paul	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Taysha Gene Therapies, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Safety	The incidence of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)	Baseline through week 52
Secondary	Exploratory Efficacy	Change from baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions Improvement (CGI-I). This 7-point scale (1 = very much improved, 7 = very much worse, etc.) is used by the clinician to assess the participant's overall performance status; higher scores indicate increased severity.	Baseline through week 52
Secondary	Exploratory Efficacy	Change from baseline in participant's status after TSHA-102 administration as assessed by Revised Motor Behavior Assessment (R-MBA). This 34-item questionnaire with scores of 0-4 will be administered by a cliniciant to indicate frequency of daily activities (behavioral/social, respiratory, motor/physical, etc.) in participants with Rett Syndrome. Higher scores correlate with greater clinical severity of disease.	Baseline through week 52
Secondary	Exploratory Efficacy	Change from baseline in participant's status after TSHA-102 administration as assessed by Rett Syndrome Behavior Questionnaire (RSBQ). The RSBQ is a 45-item questionnaire and is completed by the participant's Caregiver. Scores (0 = not true, 1 = somewhat/sometimes true, or 2 = very true) are applied to subscales including General Mood, Breathing Problems, Fear/Anxiety, Walking/Standing, etc.; higher scores indicate greater severity.	Baseline through week 52
Secondary	Exploratory Efficacy	Change from baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions-Severity (CGI-S). This 7-point scale (1 = normal - not I'll all all, 7 = extremely ill, etc.) will be administered by a clinician, based on their experience with patients with the same diagnosis. A higher score indicates greater severity of illness.	Baseline through week 52
Secondary	Exploratory Efficacy	Change from baseline in quantitative EEG findings with auditory evoked potential and visual evoked potentials (AEP and VEP). This testing will provide a measure of the electrophysiologic responses of the brain to visual and auditory stimuli.	Baseline through week 52
Secondary	Exploratory Efficacy	The percent change from the steroid-free baseline period in monthly countable seizure frequency (MCSF). This testing will provide a measure of participants with seizure freedom following administration of TSHA-102.	Baseline through week 52