Back to resultsSafety and Efficacy of TSHA-102 in Adult Females With Rett Syndrome (REVEAL Adult Study)
Primary Purpose
Rett Syndrome
Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
TSHA-102
Sponsored by
About this trial
This is an interventional treatment trial for Rett Syndrome focused on measuring Rett Syndrome, Neurodevelopmental disorder, Rett, MECP2
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 eligible to receive severe acute respiratory syndrome (SARS) coronavirus 2 (COVID-19) vaccination must be fully vaccinated against COVID-19. 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.
Sites / Locations
- Taysha Study SiteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Arm Description
Participants will be randomized to treatment with TSHA-102 or delayed treated control at the starting dose. Dose Level 1
Participants will be randomized to treatment with TSHA-102 or delayed treated control at the higher dose. Dose Level 2
Outcomes
Primary Outcome Measures
Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
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
Change from baseline in participant's status after TSHA-102 administration as assessed by the Revised Motor Behavior Assessment (R-MBA)
Change from baseline in participant's status after TSHA-102 administration as assessed by the Rett Syndrome Hand Function Scale (RSHFS)
Secondary Outcome Measures
Change from Baseline in participant's status after TSHA-102 administration as assessed by Clinical Global Impressions-Severity (CGI-S)
Change from baseline in monthly seizure frequency (52 weeks)
Change from baseline in adaptive behavior as assessed by Vineland-3
Change from Baseline in quantitative EEG findings with visual evoked potentials
Change from Baseline in quantitative EEG findings with auditory evoked potentials
Full Information
NCT ID
NCT05606614
First Posted
October 28, 2022
Last Updated
May 25, 2023
Sponsor
Taysha Gene Therapies, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05606614
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 6, 2023 (Actual)
Primary Completion Date
November 8, 2023 (Anticipated)
Study Completion Date
January 5, 2032 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Taysha Gene Therapies, Inc.
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rett Syndrome
Keywords
Rett Syndrome, Neurodevelopmental disorder, Rett, MECP2
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Participants will be randomized to treatment with TSHA-102 or delayed treated control at the starting dose.
Dose Level 1
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Participants will be randomized to treatment with TSHA-102 or delayed treated control at the higher dose.
Dose Level 2
Intervention Type
Genetic
Intervention Name(s)
TSHA-102
Intervention Description
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.
Primary Outcome Measure Information:
Title
Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs)
Time Frame
Baseline through Week 52
Title
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
Title
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
Title
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
Secondary Outcome Measure Information:
Title
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
Title
Change from baseline in monthly seizure frequency (52 weeks)
Time Frame
Baseline through Week 52
Title
Change from baseline in adaptive behavior as assessed by Vineland-3
Time Frame
Baseline through Week 52
Title
Change from Baseline in quantitative EEG findings with visual evoked potentials
Time Frame
Baseline through Week 52
Title
Change from Baseline in quantitative EEG findings with auditory evoked potentials
Time Frame
Baseline through Week 52
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 eligible to receive severe acute respiratory syndrome (SARS) coronavirus 2 (COVID-19) vaccination must be fully vaccinated against COVID-19.
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Taysha Gene Therapies Medical Information
Phone
833-489-8742
Email
medinfo@tayshagtx.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benit Maru BSc, MB ChB, MSc, PhD
Organizational Affiliation
Taysha Gene Therapies
Official's Role
Study Director
Facility Information:
Facility Name
Taysha Study Site
City
Montréal
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Taysha MedInfo
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of TSHA-102 in Adult Females With Rett Syndrome (REVEAL Adult Study)
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