Clinical trial

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

Name

TSHA-102-CL-101

Description

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.

Trial arms

Trial start

2023-03-06

Estimated PCD

2024-11-08

Trial end

2032-01-05

Status

Recruiting

Phase

Early phase I

Treatment

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.

Arms:

Cohort 1, Cohort 2

Size

Primary endpoint

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

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 18, 'type': 'ESTIMATED'}}

Updated at

2024-04-02

1 organization

1 product

1 indication

Product

TSHA-102

Indication

Rett Syndrome

Organization

Taysha Gene Therapies