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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Rett Syndrome
• Intervention / Treatment: Genetic: TSHA-102

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Taysha Gene Therapies Medical Information; Phone Number: 833-489-8742; Email: medinfo@tayshagtx.com

Study Locations

• Canada
  • Montréal, Canada
    • Recruiting
    • Taysha Study Site
    • Contact: Taysha MedInfo
• United States
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • Rush University Medical Center
      • Contact: Taysha MedInfo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Dose Level 1	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.
Experimental: Cohort 2; Dose Level 2	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)	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	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)	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)	Baseline through Week 52

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Taysha Gene Therapies, Inc.
• Investigators: Study Director: Meredith Schultz, M.D., Taysha Gene Therapies

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2023
• Primary Completion (Estimated): November 8, 2024
• Study Completion (Estimated): January 5, 2032

Study Registration Dates

• First Submitted: October 28, 2022
• First Submitted That Met QC Criteria: November 2, 2022
• First Posted (Actual): November 7, 2022

Study Record Updates

• Last Update Posted (Actual): April 2, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Neurodevelopmental disorder; Rett Syndrome; MECP2; Rett
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Syndrome; Rett Syndrome
• Other Study ID Numbers: TSHA-102-CL-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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