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Trial record 3 of 20 for:    Tay-Sachs Disease | United States

A Dose-escalation and Safety & Efficacy Study of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease

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ClinicalTrials.gov Identifier: NCT04669535
Recruitment Status : Not yet recruiting
First Posted : December 17, 2020
Last Update Posted : December 17, 2020
Sponsor:
Collaborators:
University of Massachusetts, Worcester
Massachusetts General Hospital
Information provided by (Responsible Party):
Sio Gene Therapies

Brief Summary:

The AXO-GM2-001 study is an open-label, two-stage clinical trial designed to evaluate safety and dose-escalation (Stage 1) and safety and efficacy (Stage 2) of a bilateral thalamic and intracisternal/intrathecal infusion of AXO-AAV-GM2 in pediatric participants with GM2 Gangliosidosis (also known as Tay-Sachs or Sandhoff Diseases), a set of rare and fatal pediatric neurodegenerative genetic disorders caused by defects in the HEXA (leading to Tay-Sachs disease) or HEXB (leading to Sandhoff disease) genes that encode the two subunits of the β-hexosaminidase A (HexA) enzyme. AXO-AAV-GM2 is an investigational gene therapy that aims to restore HexA function by introducing a functional copy of the HEXA and HEXB genes via co-administration of two vectors utilizing the neurotropic adeno-associated virus recombinant human 8 serotype (AAVrh.8) capsid carrying the human HEXA or HEXB cDNA.

The trial is expected to enroll pediatric participants with Tay-Sachs or Sandhoff Diseases, where infantile-onset participants will range from 6 months to 20 months old, and juvenile-onset participants will range from 2 years to 12 years old.


Condition or disease Intervention/treatment Phase
Tay-Sachs Disease Sandhoff Disease Biological: AXO-AAV-GM2 Starting Dose Biological: AXO-AAV-GM2 Low Dose Biological: AXO-AAV-GM2 Middle Dose Biological: AXO-AAV-GM2 High Dose Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Two-Stage, Dose-Escalation and Safety & Efficacy Study of Bilateral Intraparenchymal Thalamic and Intracisternal/Intrathecal Administration of AXO-AAV-GM2 in Tay-Sachs or Sandhoff Disease
Estimated Study Start Date : December 2020
Estimated Primary Completion Date : November 2024
Estimated Study Completion Date : June 2028


Arm Intervention/treatment
Experimental: AXO-AAV-GM2
AXO-AAV-GM2 infusion
Biological: AXO-AAV-GM2 Starting Dose
1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).
Other Name: AAVrh8-HEXA and AAVrh8-HEXB

Biological: AXO-AAV-GM2 Low Dose
1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).
Other Name: AAVrh8-HEXA and AAVrh8-HEXB

Biological: AXO-AAV-GM2 Middle Dose
1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).
Other Name: AAVrh8-HEXA and AAVrh8-HEXB

Biological: AXO-AAV-GM2 High Dose
1:1 ratio of AAVrh8-HEXA and AAVrh8-HEXB, administered via bilateral thalamic (BiTh) and dual intracisterna magna (ICM)/intrathecal (IT) administration into the cerebrospinal fluid (CSF).
Other Name: AAVrh8-HEXA and AAVrh8-HEXB




Primary Outcome Measures :
  1. Incidence, severity, seriousness and relatedness to treatment of treatment emergent adverse events [ Time Frame: 48 weeks (infantile-onset participants) to 96 weeks (juvenile-onset participants) ]

Secondary Outcome Measures :
  1. Number of participants with abnormal vital signs [ Time Frame: 48 weeks (infantile-onset participants) to 96 weeks (juvenile-onset participants) ]
  2. Number of participants with abnormal physical exam per investigator assessment [ Time Frame: 48 weeks (infantile-onset participants) to 96 weeks (juvenile-onset participants) ]
  3. Number of participants with abnormal clinical safety laboratory tests on blood/urine/CSF [ Time Frame: 48 weeks (infantile-onset participants) to 96 weeks (juvenile-onset participants) ]
  4. Electroencephalograms alpha, beta, delta, and theta wave frequencies (Hz) [ Time Frame: 48 weeks (infantile-onset participants) to 96 weeks (juvenile-onset participants) ]
  5. Serum cellular and antibody immune response to vector capsid/transgene [ Time Frame: 48 weeks (infantile-onset participants) to 96 weeks (juvenile-onset participants) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Months to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female subjects born between 37 - 42 weeks gestation with genetically diagnosed TSD or SD mutations of either HEXA gene or HEXB gene

    a. Juvenile-onset subjects must be ≥ 2 years old and ≤ 12 years old at time of gene transfer

    i. Diagnosis consistent with juvenile-onset TSD or SD

    b. Infantile-onset subjects must be between 6-20 months of age at the time of gene transfer

    i. Diagnosis consistent with infantile-onset TSD or SD

    ii. Current or historical ability to sit without support for at least 5 seconds

  2. Surgical readiness for gene transfer by the routes of administration confirmed by the study neurosurgeon, based on examination and magnetic resonance imaging (MRI) findings
  3. Subjects receiving off-label Zavesca® (miglustat) and/or Tanganil® (acetyl-leucine) must be willing to discontinue these therapies 30 days prior to the start of screening
  4. Ability to reliably travel to the study sites for study visits according to the Schedule of Assessments
  5. Subjects must have a swallowing evaluation test performed (within 6 months) prior to administration of gene replacement therapy

Exclusion Criteria:

  1. Presence of G269S or W574C mutation
  2. History of drug-resistant seizures or status epilepticus
  3. History and/or findings of spinal cord disease that would preclude the lumbar puncture and ICM/IT infusion procedures
  4. The subject's parent(s) or legal guardian(s) is unable to understand the nature, scope, and possible consequences of the study, or does not agree to comply with the protocol defined schedule of assessments
  5. Any prior participation in a study in which a gene therapy vector or stem cell transplantation was administered
  6. Immunizations of any kind in the month prior to screening
  7. Cardiomyopathy or other cardiac disease based on echocardiogram and/or electrocardiogram, (ECG) that in the opinion of the Investigator would deem the subject unsafe to undergo surgical gene transfer
  8. Indwelling ferromagnetic devices that would preclude MRI//MRS/DTI imaging
  9. Ongoing medical condition that is deemed by the Investigator to interfere with the conduct or assessments of the study
  10. Current clinically significant infections including any requiring systemic treatment including but not limited to human immunodeficiency virus (HIV), Hepatitis A, B, or C
  11. History of or current chemotherapy, radiotherapy or other immunosuppressive therapy within the past 30 days. Corticosteroid treatment may be permitted at the discretion of the PI
  12. Clinically significant laboratory abnormalities in liver functional tests, hematology, and blood chemistry parameters
  13. Subjects for whom any of the proposed study procedures or medications would be contraindicated
  14. Failure to thrive, defined as falling 20 percentiles (20/100) in body weight in the 3 months preceding Screening/Baseline
  15. Subject is not suitable for participation in the study in the opinion of the Principal Investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04669535


Contacts
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Contact: Clinical Trials 646-887-2651 patients@siogtx.com

Locations
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United States, Massachusetts
Massachusetts General Hospital, Center for Rare Neurological Diseases
Boston, Massachusetts, United States, 02114
Contact: Florian Eichler, MD    617-724-6510    feichler@partners.org   
Contact: Haley Andonian    617-724-1379    handonian@partners.org   
University of Massachusetts Medical Health Center
Worcester, Massachusetts, United States, 01655
Contact: Terence Flotte, MD    508-856-2107    Terry.flotte@umassmed.edu   
Contact: Karen Longtine, RN    508-856-6970    Karen.Longtine@umassmed.edu   
Sponsors and Collaborators
Sio Gene Therapies
University of Massachusetts, Worcester
Massachusetts General Hospital
Investigators
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Study Director: Erika De Boever, DDS, PhD Sio Gene Therapies
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Responsible Party: Sio Gene Therapies
ClinicalTrials.gov Identifier: NCT04669535    
Other Study ID Numbers: AXO-GM2-001
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sio Gene Therapies:
GM2 Gangliosidosis
Hexosaminidase A Deficiency
HexA Deficiency
TSD
SD
Lysosomal Storage Disorders
Tay-Sachs Disease
Sandhoff Disease
Additional relevant MeSH terms:
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Tay-Sachs Disease
Sandhoff Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Gangliosidoses, GM2
Gangliosidoses
Sphingolipidoses
Metabolism, Inborn Errors
Lipidoses
Lipid Metabolism, Inborn Errors