Clinical trial NCT04798235: First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
Official title: Phase 1/2, Open-Label Clinical Study to Evaluate the Safety and Efficacy of Intrathecal TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Infantile GM2 Gangliosidosis (Disorder)
Keywords: Tay-Sachs disease
Sandhoff disease
GM2 gangliosidosis
Lead sponsor: Queen's University
Sponsor class: OTHER
Collaborators: name: Taysha Gene Therapies, Inc.
name: GlycoNet
First posted: 2021-03-15
Enrollment: 3
Sex: ALL
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: GM2 gangliosidoses are a group of autosomal recessive neurodegenerative diseases characterized by a deficiency of the Hex A enzyme to catabolize GM2, thereby causing GM2 accumulation within cellular lysosomes.Hex A is composed of 2 subunits, α- and β-, coded by the HEXA and HEXB genes, respectively. The primary purpose of the current study is to assess the safety and tolerability of TSHA101 administered via IT injection.


Eligibility criteria: Key Inclusion Criteria:

* male or female with age less than or equal to 15 months
* diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease

Key Exclusion Criteria:

* a second neurodevelopmental disorder independent of the HEXA or HEXB
* inability to tolerate sedation or intrathecal administration
* invasive ventilatory support
* concomitant illness, allergies or known hypersensitivity to the required immunosuppression regimen

Primary outcomes:
measure: Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
timeFrame: 1 year
measure: Safety and Tolerability: Number of participants with abnormal Laboratory assessments
timeFrame: 1 year
measure: Safety and Tolerability: Electrocardiogram (ECG)
timeFrame: 1 year
Secondary outcomes:
measure: Safety and tolerability: Viral shedding analysis
timeFrame: 1 year
measure: Assessment of Immunogenicity: Biomarkers in serum
timeFrame: 1 year
measure: Assessment of Immunogenicity: Biomarkers in serum
timeFrame: 1 year
measure: Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs
timeFrame: 5 years
measure: Overall Survival
timeFrame: treatment to death from any cause, up to 5 years
measure: Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum
timeFrame: 1 year
measure: Head Control: Number of events for abnormal head control
timeFrame: 1 year
measure: Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
timeFrame: 1 year
measure: Change from Baseline in Motor Function: Modified Ashworth Scale
timeFrame: 1 year
measure: Clinical Efficacy Assessment: Progression of Hypotonia
timeFrame: 1 year
measure: Clinical Efficacy Assessment: Dysphagia
timeFrame: From onset up to 3 years, if present
Other outcomes:
Locations:
city: Kingston
country: Canada
facility: Queen's University/Kingston Health Sciences Centre
state: Ontario
Study officials:
affiliation: Queen's University
name: Anupam Sehgal, MBBS
role: PRINCIPAL_INVESTIGATOR
References: