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Trial record 2 of 10 for:    Recruiting, Not yet recruiting, Active, not recruiting Studies | Gm1 gangliosidosis

A Safety and Efficacy Study of LYS-GM101 Gene Therapy in Patients With GM1 Gangliosidosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04273269
Recruitment Status : Not yet recruiting
First Posted : February 18, 2020
Last Update Posted : February 18, 2020
Sponsor:
Information provided by (Responsible Party):
LYSOGENE

Brief Summary:
LYS-GM101 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the central nervous system. This study will assess, in a 2-stage adaptive-design, the safety and efficacy of treatment in subjects with infantile and juvenile GM1 gangliosidosis.

Condition or disease Intervention/treatment Phase
GM1 Gangliosidosis Genetic: LYS-GM101 Phase 1 Phase 2

Detailed Description:
GM1 gangliosidosis is a fatal autosomal recessive disease caused by mutations in the GLB1 gene leading to accumulation of GM1 gangliosides in neurons and progressive neurodegeneration. There are three pediatric subtypes: early infantile, late infantile and juvenile. This is an interventional, multicenter, single-arm, dose escalation study of LYS-GM101. In the first stage of the study, two doses of LYS-GM101 will be studied in 6 subjects who have infantile GM1 gangliosidosis. The second stage of the study will include both infantile and juvenile patients.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Adaptive-Design Study of Intracisternal Adenoassociated Viral Vector Serotype rh.10 Carrying the Human β-Galactosidase cDNA for Treatment of GM1 Gangliosidosis
Estimated Study Start Date : April 2020
Estimated Primary Completion Date : June 2025
Estimated Study Completion Date : June 2025


Arm Intervention/treatment
Experimental: 3.2x10^12 vg/Kg LYS-GM101
Subjects will receive a single infusion: 3.2x10^12 vg/Kg LYS-GM101
Genetic: LYS-GM101
LYS-GM101 is an adeno-associated viral vector serotype rh.10 (AAVrh.10) carrying the human β-galactosidase gene, formulated as a solution for injection

Experimental: 8.0x10^12 vg/Kg LYS-GM101
Subjects will receive a single infusion: 8.0x10^12 vg/Kg LYS-GM101
Genetic: LYS-GM101
LYS-GM101 is an adeno-associated viral vector serotype rh.10 (AAVrh.10) carrying the human β-galactosidase gene, formulated as a solution for injection




Primary Outcome Measures :
  1. Stage 1: Physical examination by body system [ Time Frame: Up to 6 months (multiple visits) ]
    Physical examination by body system: normal/abnormal and change from previous assessment

  2. Stage 1: Neurological examination [ Time Frame: Up to 6 months (multiple visits) ]
    Neurological examination: normal/abnormal motor activity and coordination, and change from previous assessment

  3. Stage 1: Vital signs: change from baseline in heart rate [ Time Frame: Up to 6 months (multiple visits) ]
  4. Stage 1: Vital signs: change from baseline in body temperature [ Time Frame: Up to 6 months (multiple visits) ]
  5. Stage 1: Vital signs: change from baseline in diastolic and systolic blood pressure [ Time Frame: Up to 6 months (multiple visits) ]
  6. Stage 1: Imaging: presence of bleeding post-administration [ Time Frame: Up to 6 months (multiple visits) ]
  7. Stage 1: Change from baseline in biochemistry, coagulation and hematology laboratory parameters [ Time Frame: Up to 6 months (multiple visits) ]
  8. Stage 1: Incidence of treatment-emergent adverse event and serious adverse events [ Time Frame: Up to 6 months (multiple visits) ]
  9. Stage 1: Assessment of humoral immune response by measurement of antibodies anti-AAV and anti-beta-galactosidase (ELISA) and cellular immune response by beta-galactosidase-specific T-cell proliferation assay [ Time Frame: Up to 6 months (multiple visits) ]

Secondary Outcome Measures :
  1. Motor Function [ Time Frame: Up to 2 years (multiple visits) ]
    Assess change from baseline in motor function using the Hammersmith Infant Neurological Evaluation (HINE) or Hammersmith Functional Motor Scale-Expanded (HFMSE) instruments

  2. Brain MRI [ Time Frame: Up to 2 years (multiple visits) ]
    Assess brain atrophy and brain volume

  3. Developmental changes (VABS-II) [ Time Frame: Up to 2 years (multiple visits) ]
    Assess developmental change from baseline in the Vineland Adaptive Behavior Scale-II-Expanded Interview (VABS-II) instrument

  4. Developmental changes (BSID-III or KABC-II) [ Time Frame: Up to 2 years (multiple visits) ]
    Assess developmental change from baseline in the Bayley Scales of Infant and Toddler Development, 3rd Edition (BSID-III) or the Kaufman Assessment Battery for Children, 2nd Edition (KABC-II) instruments

  5. Blood and cerebrospinal fluid (CSF) biomarkers (beta-galactosidase) [ Time Frame: Up to 2 years (multiple visits) ]
    Assess change in beta-galactosidase activity measured from baseline

  6. Blood and cerebrospinal fluid (CSF) biomarkers (GM1 ganglioside) [ Time Frame: Up to 2 years (multiple visits) ]
    Assess change in GM1 ganglioside level measured from baseline



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Documented GM1 gangliosidosis diagnosis based on genotyping confirming the β-gal gene mutations and/or documented deficiency of β-gal enzyme by laboratory testing
  • Children with early infantile GM1 gangliosidosis less than 12 months of age with ability to swallow
  • Children with late infantile GM1 gangliosidosis less than 3 years of age with ability to sit (arm support or props are permitted)
  • Children with juvenile GM1 gangliosidosis (only in Stage 2)

Exclusion Criteria:

  • Uncontrolled seizure disorder. Patients who are stable on anti-convulsive medications may be included
  • More than 40% brain atrophy as measured by MRI total brain volume at screening
  • Current participation in a clinical trial of another investigational medicinal product
  • Past participation in gene therapy trials
  • History of hematopoietic stem cell transplantation
  • Any condition that would contraindicate treatment with immunosuppressant therapy
  • Presence of concomitant medical condition or anatomical abnormality precluding lumbar puncture or intracisternal injection
  • Presence of any permanent items (e.g., metal braces) precluding undergoing MRI
  • History of non-GM1 gangliosidosis medical condition that would confound scientific rigor or interpretation of results
  • Rare and unrelated serious comorbidities, e.g., Down syndrome, intraventricular hemorrhage in the new-born period, or extreme low birth weight (<1500 grams)
  • Any vaccination 1 month prior to the planned immunosuppression treatment
  • Serology consistent with HIV exposure or consistent with active hepatitis B or C infection
  • Grade 2 or higher lab abnormalities for Liver function tests (LFT), bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT), and partial thromboplastin time (PTT), according to CTCAE v5.0

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): NCT04273269


Contacts
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Contact: Lysogene Trial Inquiries +33 (0)1 41 43 03 90 patientadvocacy@lysogene.com

Sponsors and Collaborators
LYSOGENE
Investigators
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Study Director: Clinical Operations LYSOGENE
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Responsible Party: LYSOGENE
ClinicalTrials.gov Identifier: NCT04273269    
Other Study ID Numbers: P1-GM-101
First Posted: February 18, 2020    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020

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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 LYSOGENE:
GM1 Gangliosidosis
Lysosomal Storage Disease
Landing Disease
Additional relevant MeSH terms:
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Gangliosidoses
Gangliosidosis, GM1
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders