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

• ClinicalTrials.gov Identifier: NCT06152237
• Recruitment Status: Recruiting
• First Posted: November 30, 2023
• Last Update Posted: February 14, 2024
• Sponsor: Taysha Gene Therapies, Inc.
• Information provided by (Responsible Party): Taysha Gene Therapies, Inc.

Tracking Information

• First Submitted Date: November 21, 2023
• First Posted Date: November 30, 2023
• Last Update Posted Date: February 14, 2024
• Actual Study Start Date: December 12, 2023
• Estimated Primary Completion Date: November 2, 2028 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2023)

Primary Safety [ Time Frame: Baseline through week 52 ]

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

Original Primary Outcome Measures (submitted: November 21, 2023)

Primary Safety [ Time Frame: Baseline through week 52 ]

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

Current Secondary Outcome Measures (submitted: December 19, 2023)

• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  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.
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  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.
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  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.
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  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.
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  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.
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  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.

Original Secondary Outcome Measures (submitted: November 21, 2023)

• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  Change from baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions Improvement (CGI-I).
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  Change from baseline in participant's status after TSHA-102 administration as assessed by Revised Motor Behavior Assessment (R-MBA).
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  Change from baseline in participant's status after TSHA-102 administration as assessed by Rett Syndrome Behavior Questionnaire (RSBQ).
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  Change from baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions-Severity (CGI-S).
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  Change from baseline in quantitative EEG findings with auditory and visual evoked potentials (AEP and VEP).
• Exploratory Efficacy [ Time Frame: Baseline through week 52 ]
  Change from the steroid-free baseline period in monthly countable seizure frequency (MCSF).

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Rett 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.

Study Arms

• Experimental: Cohort 1
  Dose Level 1
  Intervention: Genetic: TSHA-102
• Experimental: Cohort 2
  Dose Level 2
  Intervention: Genetic: TSHA-102

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 21, 2023): 6
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2, 2031
• Estimated Primary Completion Date: November 2, 2028 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 5 Years to 8 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Taysha Gene Therapies Medical Information; 1-833-489-8742; medinfo@tayshagtx.com

• Listed Location Countries: United Kingdom, United States

Administrative Information

• NCT Number: NCT06152237
• Other Study ID Numbers: TSHA-102-CL-102
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Taysha Gene Therapies, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taysha Gene Therapies, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Benit Maru, Bsc, MB ChB, MSc, PhD; Taysha Gene Therapies

• PRS Account: Taysha Gene Therapies, Inc.
• Verification Date: February 2024