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

• ClinicalTrials.gov Identifier: NCT05606614
• Recruitment Status: Recruiting
• First Posted: November 7, 2022
• Last Update Posted: April 2, 2024
• Sponsor: Taysha Gene Therapies, Inc.
• Information provided by (Responsible Party): Taysha Gene Therapies, Inc.

Tracking Information

• First Submitted Date: October 28, 2022
• First Posted Date: November 7, 2022
• Last Update Posted Date: April 2, 2024
• Actual Study Start Date: March 6, 2023
• Estimated Primary Completion Date: November 8, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 2, 2022)

• Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs) [ 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) scale, adapted to Rett syndrome [ Time Frame: Baseline through Week 52 ]
• Change from baseline in participant's status after TSHA-102 administration as assessed by the Revised Motor Behavior Assessment (R-MBA) [ Time Frame: Baseline through Week 52 ]
• Change from baseline in participant's status after TSHA-102 administration as assessed by the Rett Syndrome Hand Function Scale (RSHFS) [ Time Frame: Baseline through Week 52 ]

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 2, 2022)

• Change from Baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions-Severity (CGI-S) [ Time Frame: Baseline through Week 52 ]
• Change from baseline in monthly seizure frequency (52 weeks) [ Time Frame: Baseline through Week 52 ]
• Change from baseline in adaptive behavior as assessed by Vineland-3 [ Time Frame: Baseline through Week 52 ]
• Change from Baseline in quantitative EEG findings with visual evoked potentials [ Time Frame: Baseline through Week 52 ]
• Change from Baseline in quantitative EEG findings with auditory evoked potentials [ Time Frame: Baseline through Week 52 ]

• Original Secondary Outcome Measures: Same as current
• 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 Adult Females With Rett Syndrome (REVEAL Adult Study)
• Official Title: Open-label, Randomized, Dose-escalation and Dose-expansion Study of the Safety and Preliminary Efficacy of a Single Intrathecal Administration of TSHA-102, an AAV9-Delivered Gene Therapy, in the Treatment of Adult Females With Rett Syndrome

Brief Summary

The REVEAL Adult Study is a multi-center, Phase 1/2 open-label, dose-escalation study of TSHA-102, an investigational gene therapy, in adult females with Rett syndrome. The safety, tolerability, and preliminary efficacy of two dose levels will be evaluated.

The study duration is estimated to be up to 63 months.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• 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): 18
• Original Estimated Enrollment (submitted: November 2, 2022): 12
• Estimated Study Completion Date: January 5, 2032
• Estimated Primary Completion Date: November 8, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Participant has a clinical diagnosis of classical/typical Rett syndrome with a documented pathogenic mutation of the methyl-CpG-binding protein 2 (MECP2) gene that results in loss of function.
• Participants must be willing 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 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 a MECP2 mutation that does not cause Rett syndrome.
• Participant requires invasive ventilatory support.
• Participant has contraindications for IT administration of TSHA-102 or lumbar puncture procedure, or other medical conditions, or contraindications to any medications required for IT administration.
• Participant has uncontrolled seizures or a history of status epilepticus within the 3 months prior to enrollment.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 12 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT05606614
• Other Study ID Numbers: TSHA-102-CL-101
• 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: Meredith Schultz, M.D.; Taysha Gene Therapies

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