Ignite Creation Date:
2025-12-24 @ 10:30 PM
Ignite Modification Date:
2025-12-25 @ 8:03 PM
Study NCT ID:
NCT04798235
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2023-05-09
First Post:
2021-02-22
Is Possible Gene Therapy:
True
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D013661', 'term': 'Tay-Sachs Disease'}, {'id': 'D012497', 'term': 'Sandhoff Disease'}, {'id': 'D020143', 'term': 'Gangliosidoses, GM2'}], 'ancestors': [{'id': 'D005733', 'term': 'Gangliosidoses'}, {'id': 'D013106', 'term': 'Sphingolipidoses'}, {'id': 'D020140', 'term': 'Lysosomal Storage Diseases, Nervous System'}, {'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008064', 'term': 'Lipidoses'}, {'id': 'D008052', 'term': 'Lipid Metabolism, Inborn Errors'}, {'id': 'D016464', 'term': 'Lysosomal Storage Diseases'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D052439', 'term': 'Lipid Metabolism Disorders'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 3}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2021-03-12', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-05', 'completionDateStruct': {'date': '2027-03-12', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2023-05-08', 'studyFirstSubmitDate': '2021-02-22', 'studyFirstSubmitQcDate': '2021-03-11', 'lastUpdatePostDateStruct': {'date': '2023-05-09', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2021-03-15', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-03-12', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)', 'timeFrame': '1 year', 'description': 'Incidence, severity, and relatedness of TEAEs'}, {'measure': 'Safety and Tolerability: Number of participants with abnormal Laboratory assessments', 'timeFrame': '1 year', 'description': 'Number of participants with Changes from Baseline in laboratory assessments'}, {'measure': 'Safety and Tolerability: Electrocardiogram (ECG)', 'timeFrame': '1 year', 'description': 'Changes from Baseline in 12-lead ECG findings in QT interval'}], 'secondaryOutcomes': [{'measure': 'Safety and tolerability: Viral shedding analysis', 'timeFrame': '1 year', 'description': 'Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)'}, {'measure': 'Assessment of Immunogenicity: Biomarkers in serum', 'timeFrame': '1 year', 'description': 'Summary of neutralizing antibodies (NAbs) titers for adeno-associated virus, serotype 9 (AAV9) and Hex A'}, {'measure': 'Assessment of Immunogenicity: Biomarkers in serum', 'timeFrame': '1 year', 'description': 'Summary of total antibodies (TAbs) titers for AAV9 and Hex A'}, {'measure': 'Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs', 'timeFrame': '5 years', 'description': 'Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A'}, {'measure': 'Overall Survival', 'timeFrame': 'treatment to death from any cause, up to 5 years', 'description': 'Estimated using the Kaplan-Meier method'}, {'measure': 'Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum', 'timeFrame': '1 year', 'description': 'Change from baseline'}, {'measure': 'Head Control: Number of events for abnormal head control', 'timeFrame': '1 year', 'description': 'change from Baseline'}, {'measure': "Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)", 'timeFrame': '1 year', 'description': '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.'}, {'measure': 'Change from Baseline in Motor Function: Modified Ashworth Scale', 'timeFrame': '1 year', 'description': '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.'}, {'measure': 'Clinical Efficacy Assessment: Progression of Hypotonia', 'timeFrame': '1 year', 'description': 'Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit'}, {'measure': 'Clinical Efficacy Assessment: Dysphagia', 'timeFrame': 'From onset up to 3 years, if present', 'description': 'Assessment of the dysphagia events- assessed as present or absent.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Tay-Sachs disease', 'Sandhoff disease', 'GM2 gangliosidosis'], 'conditions': ['Infantile GM2 Gangliosidosis (Disorder)']}, 'referencesModule': {'references': [{'pmid': '38205442', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '15 Months', 'healthyVolunteers': False, 'eligibilityCriteria': 'Key Inclusion Criteria:\n\n* male or female with age less than or equal to 15 months\n* diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease\n\nKey Exclusion Criteria:\n\n* a second neurodevelopmental disorder independent of the HEXA or HEXB\n* inability to tolerate sedation or intrathecal administration\n* invasive ventilatory support\n* concomitant illness, allergies or known hypersensitivity to the required immunosuppression regimen'}, 'identificationModule': {'nctId': 'NCT04798235', 'briefTitle': 'First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis', 'organization': {'class': 'OTHER', 'fullName': "Queen's University"}, 'officialTitle': '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', 'orgStudyIdInfo': {'id': 'TSHA-101-IST-001'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'TSHA-101', 'description': 'Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage', 'interventionNames': ['Biological: TSHA-101']}], 'interventions': [{'name': 'TSHA-101', 'type': 'BIOLOGICAL', 'description': 'AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection', 'armGroupLabels': ['TSHA-101']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'K7L 2V7', 'city': 'Kingston', 'state': 'Ontario', 'country': 'Canada', 'facility': "Queen's University/Kingston Health Sciences Centre", 'geoPoint': {'lat': 44.22976, 'lon': -76.48098}}], 'overallOfficials': [{'name': 'Anupam Sehgal, MBBS', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': "Queen's University"}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Dr. Anupam Sehgal', 'class': 'OTHER'}, 'collaborators': [{'name': 'Taysha Gene Therapies, Inc.', 'class': 'INDUSTRY'}, {'name': 'GlycoNet', 'class': 'UNKNOWN'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Primary Investigator', 'investigatorFullName': 'Dr. Anupam Sehgal', 'investigatorAffiliation': "Queen's University"}}}}