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A Phase 1/2/3 Study of TSHA-102 Gene Therapy in Females With Rett Syndrome (REVEAL Pivotal Study)

Phase 3Active Not RecruitingNCT05606614
Taysha Gene Therapies, Inc.17 enrolled

Overview

The primary objectives of this study are to evaluate the safety of a single intrathecal (IT) dose of TSHA-102 in females with typical Rett syndrome, to select the TSHA-102 dose with the best benefit/risk profile based on the totality of safety and efficacy data and to evaluate the efficacy and safety of TSHA-102 at the selected dose.

REVEAL Part A (Phase 1/2) is an open-label safety and dose-finding study designed to evaluate the safety and preliminary efficacy of two dose levels of TSHA-102 to establish initial safety of TSHA-102 and select a safe and efficacious dose for further evaluation. Enrollment of 6 participants in Part A is complete. REVEAL Part B (Phase 3) will evaluate the efficacy and safety of TSHA-102 at the dose level 2 determined in Part A in 15 females ages 6 to \<22 years with typical Rett syndrome. TSHA-102 is designed to target the genetic root cause of Rett syndrome by regulating the expression of MECP2 in cells. Each participant will be followed for the observation period of 5 years after TSHA-102 administration in Part A and B.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

17

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: 6 YearsMax age: 21 Years
Medical Language ↔ Plain English
Inclusion Criteria: * Females between the ages of 12 and \<22 in Part A (closed) and females between the ages of 6 and \<22 in Part B (pivotal cohort). * Participant has a clinical diagnosis of classic/typical Rett syndrome with a documented pathogenic mutation of the methyl-CpG-binding protein 2 (MECP2) gene that results in loss of gene function. * Participants must be willing to receive blood or blood products for the treatment of an AE if medically needed. * Participants and parent/caregiver must agree to reside within easy access to the study site prior to the baseline visit and at least 3 months after TSHA-102 treatment 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 or had grossly abnormal psychomotor development in the first 6 months of life. * Participant has a diagnosis of atypical Rett syndrome or a MECP2 gene mutation that does not cause Rett syndrome. * Participant requires invasive ventilatory support. Note: Other protocol defined inclusion/exclusion criteria may apply

Locations (9)

City of Hope

Duarte, California, United States

UC San Diego

La Jolla, California, United States

UC San Francisco Benioff Children's Hospital

Oakland, California, United States

Rush University Medical Center

Outcomes

Primary Outcomes

Part A: Safety and Tolerability of TSHA-102

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

Time frame: Baseline through Week 52

Part B: Efficacy of TSHA-102

Change from baseline in percentage of participants who gain or regain any one or more of the 28 items from the Developmental Milestones Assessment (DMA), which are video recorded and scored by independent, blinded central raters.

Time frame: Baseline through Week 52

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Chicago, Illinois, United States

Kennedy Krieger Institute

Baltimore, Maryland, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Washington University, St. Louis

St Louis, Missouri, United States

UT Southwestern Children's Medical Center

Dallas, Texas, United States

CHU St. Justine

Montreal, Quebec, Canada