Clinical trial NCT05606614: Safety and Efficacy of TSHA-102 in Adolescent and Adult Females With Rett Syndrome (REVEAL Adult Study)
Official title: REVEAL Adult Study: An Open-label, Randomized, Doseescalation- 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Rett Syndrome
Keywords: Rett Syndrome
Neurodevelopmental disorder
Rett
MECP2
Lead sponsor: Taysha Gene Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-07
Enrollment: 18
Sex: FEMALE
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Baseline through Week 52
measure: 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
timeFrame: Baseline through Week 52
measure: Change from baseline in participant's status after TSHA-102 administration as assessed by the Revised Motor Behavior Assessment (R-MBA)
timeFrame: Baseline through Week 52
measure: Change from baseline in participant's status after TSHA-102 administration as assessed by the Rett Syndrome Hand Function Scale (RSHFS)
timeFrame: Baseline through Week 52
Secondary outcomes:
measure: Change from Baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions-Severity (CGI-S)
timeFrame: Baseline through Week 52
measure: Change from baseline in monthly seizure frequency (52 weeks)
timeFrame: Baseline through Week 52
measure: Change from baseline in adaptive behavior as assessed by Vineland-3
timeFrame: Baseline through Week 52
measure: Change from Baseline in quantitative EEG findings with visual evoked potentials
timeFrame: Baseline through Week 52
measure: Change from Baseline in quantitative EEG findings with auditory evoked potentials
timeFrame: Baseline through Week 52
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UC San Diego
state: California
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Saint Paul
country: United States
facility: Gillette Children's Hospital
state: Minnesota
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Montréal
country: Canada
facility: CHU St. Justine
state: Quebec
Study officials:
affiliation: Taysha Gene Therapies
name: Laura Pisani, M.D.
role: STUDY_DIRECTOR
References: