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
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
Taysha Gene Therapies, Inc. |
United States, United Kingdom,
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 |
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