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

Phase 2Active Not RecruitingNCT06152237

Taysha Gene Therapies, Inc.6 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Rett Syndrome

Interventions

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.

Eligibility

Sex: FEMALEMin age: 5 YearsMax age: 8 Years

Medical Language ↔ Plain English

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.

Locations (5)

Rush University Medical Center & Children's Hospital

Chicago, Illinois, United States

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States

Washington University, St. Louis

St Louis, Missouri, United States

CHU Ste-Justine

Montreal, Quebec, Canada

Outcomes

Primary Outcomes

Primary Safety

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

Time frame: Baseline through week 52

Secondary Outcomes

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.

Time frame: Baseline through week 52

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.

Time frame: Baseline through week 52

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.

Time frame: Baseline through week 52

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.

Data from ClinicalTrials.gov

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