NCT04798235

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.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
3

participants targeted

Target at below P25 for phase_1

Timeline
10mo left

Started Mar 2021

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress86%
Mar 2021Mar 2027

First Submitted

Initial submission to the registry

February 22, 2021

Completed
18 days until next milestone

Study Start

First participant enrolled

March 12, 2021

Completed
3 days until next milestone

First Posted

Study publicly available on registry

March 15, 2021

Completed
6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 12, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 12, 2027

Last Updated

May 9, 2023

Status Verified

May 1, 2023

Enrollment Period

6 years

First QC Date

February 22, 2021

Last Update Submit

May 8, 2023

Conditions

Infantile GM2 Gangliosidosis (Disorder)

Keywords

Tay-Sachs diseaseSandhoff diseaseGM2 gangliosidosis

Outcome Measures

Primary Outcomes (3)

  • Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)

    Incidence, severity, and relatedness of TEAEs

    1 year

  • Safety and Tolerability: Number of participants with abnormal Laboratory assessments

    Number of participants with Changes from Baseline in laboratory assessments

    1 year

  • Safety and Tolerability: Electrocardiogram (ECG)

    Changes from Baseline in 12-lead ECG findings in QT interval

    1 year

Secondary Outcomes (11)

  • Safety and tolerability: Viral shedding analysis

    1 year

  • Assessment of Immunogenicity: Biomarkers in serum

    1 year

  • Assessment of Immunogenicity: Biomarkers in serum

    1 year

  • Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs

    5 years

  • Overall Survival

    treatment to death from any cause, up to 5 years

  • +6 more secondary outcomes

Study Arms (1)

TSHA-101

EXPERIMENTAL

Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage

Biological: TSHA-101

Interventions

TSHA-101BIOLOGICAL

AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection

TSHA-101

Eligibility Criteria

AgeUp to 15 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Queen's University/Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Location

Related Publications (1)

  • Ryckman AE, Deschenes NM, Quinville BM, Osmon KJL, Mitchell M, Chen Z, Gray SJ, Walia JS. Intrathecal delivery of a bicistronic AAV9 vector expressing beta-hexosaminidase A corrects Sandhoff disease in a murine model: A dosage study. Mol Ther Methods Clin Dev. 2023 Dec 5;32(1):101168. doi: 10.1016/j.omtm.2023.101168. eCollection 2024 Mar 14.

    PMID: 38205442DERIVED

MeSH Terms

Conditions

Tay-Sachs DiseaseSandhoff DiseaseGangliosidoses, GM2

Condition Hierarchy (Ancestors)

GangliosidosesSphingolipidosesLysosomal Storage Diseases, Nervous SystemBrain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesLipidosesLipid Metabolism, Inborn ErrorsLysosomal Storage DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesLipid Metabolism Disorders

Study Officials

  • Anupam Sehgal, MBBS

    Queen's University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Primary Investigator

Study Record Dates

First Submitted

February 22, 2021

First Posted

March 15, 2021

Study Start

March 12, 2021

Primary Completion (Estimated)

March 12, 2027

Study Completion (Estimated)

March 12, 2027

Last Updated

May 9, 2023

Record last verified: 2023-05

Data Sharing

IPD Sharing
Will not share

Locations

CA(1)