Rett Syndrome
Conditions
Keywords
Rett Syndrome, Neurodevelopmental disorder, Rett, MECP2, AAV9, Typical Rett Syndrome, Classic Rett Syndrome, RTT, Rett Disorder, Retts, MECP2-Related Disorder, Gene Therapy, Intrathecal Administration, Genetic Diseases, X-Linked, Nervous System Diseases, Developmental Regression, TSHA-102, miRARE, Self-complementary Vector, Neurologic Manifestations, Intellectual Disability, Pathologic Process, X-Linked Intellectual Disability, Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Brief summary
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.
Detailed description
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.
Interventions
GENETICTSHA-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.
Sponsors
Taysha Gene Therapies, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Central raters assessing the gain or regain of a developmental milestone from videos are blinded to the timing of each video.
Intervention model description
The study treatment will be delivered via intrathecal (IT) injection.
Eligibility
Sex/Gender
FEMALE
Age
6 Years to 21 Years
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Safety and Tolerability of TSHA-102 | Baseline through Week 52 | Proportions of participants experiencing any treatment-emergent adverse events (AEs) and serious adverse events (SAEs) |
| Part B: Efficacy of TSHA-102 | Baseline through Week 52 | 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. |
Countries
Canada, United States
Contacts
STUDY_DIRECTORMedical Monitor, M.D.
Taysha Gene Therapies
Outcome results
None listed