Infantile GM2 Gangliosidosis (Disorder)Phase 1/2NCT04798235
First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
A Phase 1/2 study testing TSHA-101 in people with Infantile GM2 Gangliosidosis (Disorder), run by Dr. Anupam Sehgal at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 15 months
- Conditions the study is for
- Infantile GM2 Gangliosidosis (Disorder)
- What is being tested?
- TSHA-101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteCanada
- Study dates
- 12 Mar 2021to 12 Mar 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 15 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- male or female with age less than or equal to 15 months
- diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Queen's University/Kingston Health Sciences Centre
Kingston, Ontario, K7L 2V7
About this study
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
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.
- Conditions
- Infantile GM2 Gangliosidosis (Disorder)
- Being tested
- TSHA-101
- Keywords
- Tay-Sachs disease, Sandhoff disease, GM2 gangliosidosis
- Medical subject headings
- Tay-Sachs Disease, Sandhoff Disease, Gangliosidoses, GM2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TSHA-101Biological
AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection
| Study group | Role | What they receive |
|---|---|---|
| TSHA-101 | Experimental | Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage Receives: Biological: TSHA-101 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
Incidence, severity, and relatedness of TEAEs
Measured: 1 year
Safety and Tolerability: Number of participants with abnormal Laboratory assessments
Number of participants with Changes from Baseline in laboratory assessments
Measured: 1 year
Safety and Tolerability: Electrocardiogram (ECG)
Changes from Baseline in 12-lead ECG findings in QT interval
Measured: 1 year
Secondary outcomes (11)
Safety and tolerability: Viral shedding analysis
Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)
Measured: 1 year
Assessment of Immunogenicity: Biomarkers in serum
Summary of neutralizing antibodies (NAbs) titers for adeno-associated virus, serotype 9 (AAV9) and Hex A
Measured: 1 year
Assessment of Immunogenicity: Biomarkers in serum
Summary of total antibodies (TAbs) titers for AAV9 and Hex A
Measured: 1 year
Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs
Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A
Measured: 5 years
Overall Survival
Estimated using the Kaplan-Meier method
Measured: treatment to death from any cause, up to 5 years
Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum
Change from baseline
Measured: 1 year
Head Control: Number of events for abnormal head control
change from Baseline
Measured: 1 year
Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
The test consists of 16 items (body parts), where each item is tested for both sides of the body, left and right. The best score is taken for each item (with a maximum score of 4), and the scores are summed over all 16 items with a possible total CHOP-INTEND score of 64.
Measured: 1 year
Change from Baseline in Motor Function: Modified Ashworth Scale
change from Baseline. Increase or decrease of muscle tone will be measured by the Modified Ashworth Scale. Frequency counts and percentages will be presented by score (0, 1, 1+, 2, 3, and 4), muscle, side, and visit for the safety population. Flexion and extension of the knee and elbow will be measured on both sides, along with hip adduction and abduction on both sides of the body.
Measured: 1 year
Clinical Efficacy Assessment: Progression of Hypotonia
Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit
Measured: 1 year
Clinical Efficacy Assessment: Dysphagia
Assessment of the dysphagia events- assessed as present or absent.
Measured: From onset up to 3 years, if present
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2021
- Study start12 Mar 2021
- Primary completion12 Mar 2027 (estimated)
- Study completion12 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Infantile GM2 Gangliosidosis (Disorder)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Anupam Sehgal
- Sponsor type
- University, hospital or other
- Collaborators
- Taysha Gene Therapies, Inc., GlycoNet
- Responsible party
- Sponsor-investigator, Dr. Anupam Sehgal, Queen's University
- Investigators
- Anupam Sehgal, MBBS, Principal investigator, Queen's University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04798235
- Sponsor's protocol ID
- TSHA-101-IST-001
- Status last verified
- May 2023
- First submitted
- 22 Feb 2021
- Last updated
- 9 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38205442
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04798235
- Acronym / sponsor ID
- TSHA-101-IST-001
- Conditions
- Infantile GM2 Gangliosidosis (Disorder)
- Keywords
- Tay-Sachs disease, Sandhoff disease, GM2 gangliosidosis
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Dr. Anupam SehgalUniversity, hospital or other
- Collaborators
- Taysha Gene Therapies, Inc., GlycoNet
- Study start
- 12 Mar 2021 (actual)
- Primary completion
- 12 Mar 2027 (estimated)
- Study completion
- 12 Mar 2027 (estimated)
- First posted
- 15 Mar 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TSHA-101 | Experimental | Biological: TSHA-101Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage |
Who may qualify
- Ages
- Up to 15 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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 (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TSHA-101AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection | Biological | TSHA-101 |
Primary outcome
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
Time frame: 1 year
Incidence, severity, and relatedness of TEAEs
Safety and Tolerability: Number of participants with abnormal Laboratory assessments
Time frame: 1 year
Number of participants with Changes from Baseline in laboratory assessments
Safety and Tolerability: Electrocardiogram (ECG)
Time frame: 1 year
Changes from Baseline in 12-lead ECG findings in QT interval
11 secondary outcomes
Safety and tolerability: Viral shedding analysis
Time frame: 1 year
Assessment of Immunogenicity: Biomarkers in serum
Time frame: 1 year
Assessment of Immunogenicity: Biomarkers in serum
Time frame: 1 year
Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs
Time frame: 5 years
Overall Survival
Time frame: treatment to death from any cause, up to 5 years
Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum
Time frame: 1 year
Head Control: Number of events for abnormal head control
Time frame: 1 year
Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
Time frame: 1 year
Change from Baseline in Motor Function: Modified Ashworth Scale
Time frame: 1 year
Clinical Efficacy Assessment: Progression of Hypotonia
Time frame: 1 year
Clinical Efficacy Assessment: Dysphagia
Time frame: From onset up to 3 years, if present
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2023.
- Derived from this study: PubMed 38205442Ryckman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anupam Sehgal, MBBS principal investigator
Queen's University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TSHA-101 in people with Infantile GM2 Gangliosidosis (Disorder), run by Dr. Anupam Sehgal at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 9 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs) (time frame: 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04798235, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2023.