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

NCT04273269 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: P1-GM-101
• Study Type: interventional
• Target: 5
• Locations: 3 countries
• Sites: 3

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 GM1 gangliosidosis.

Conditions

GM1 Gangliosidosis

Keywords

GM1 Gangliosidosis; Lysosomal Storage Disease; Landing Disease

Outcome Measures

Primary Outcomes (10)

• Stage 1: Physical examination by body system

  Physical examination by body system: normal/abnormal and change from previous assessment

  Up to 6 months (multiple visits)

• Stage 1: Neurological examination

  Neurological examination: normal/abnormal motor activity and coordination, and change from previous assessment

  Up to 6 months (multiple visits)

• Stage 1: Vital signs: change from baseline in heart rate

  Vital signs: change from baseline in heart rate

  Up to 6 months (multiple visits)

• Stage 1: Vital signs: change from baseline in body temperature

  Vital signs: change from baseline in body temperature

  Up to 6 months (multiple visits)

• Stage 1: Vital signs: change from baseline in diastolic and systolic blood pressure

  Vital signs: change from baseline in diastolic and systolic blood pressure

  Up to 6 months (multiple visits)

• Stage 1: Imaging: presence of bleeding post-administration

  Imaging: presence of bleeding post-administration

  Up to 6 months (multiple visits)

• Stage 1: Change from baseline in biochemistry laboratory parameters

  Change from baseline in biochemistry laboratory parameters

  Up to 6 months (multiple visits)

• Stage 1: Change from baseline in coagulation and hematology laboratory parameters

  Change from baseline in coagulation and hematology laboratory parameters

  Up to 6 months (multiple visits)

• Stage 1: Incidence of treatment-emergent adverse event and serious adverse events

  Incidence of treatment-emergent adverse event and serious adverse events

  Up to 6 months (multiple visits)

• 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

  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

  Up to 6 months (multiple visits)

Secondary Outcomes (6)

• Motor Function

  Up to 2 years (multiple visits)

• Brain MRI

  Up to 2 years (multiple visits)

• Developmental changes (VABS-II)

  Up to 2 years (multiple visits)

• Developmental changes (BSID-III or KABC-II)

  Up to 2 years (multiple visits)

• Blood and cerebrospinal fluid (CSF) biomarkers (beta-galactosidase)

  Up to 2 years (multiple visits)

Study Arms (1)

8x10^12 vg/Kg LYS-GM101

EXPERIMENTAL

Subjects will receive a single infusion: 8x10\^12 vg/Kg LYS-GM101

Genetic: LYS-GM101

Interventions

LYS-GM101 GENETIC

LYS-GM101 is an adeno-associated viral vector serotype rh.10 (AAVrh.10) carrying the human β-galactosidase gene, formulated as a suspension for injection

8x10^12 vg/Kg LYS-GM101

Eligibility Criteria

• Age: Up to 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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 a gene therapy trial
• 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, extreme low birth weight (\<1500 grams) or known bleeding disorders
• Any vaccination 1 month prior to the planned immunosuppressant 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

Sponsors & Collaborators

• LYSOGENE: lead

Study Sites (3)

Children's Hospital of Orange County (CHOC)

Orange, California, 92868, United States

Location

Hôpital Armand-Trousseau, Centre de Référence des Maladies Lysosomales (CRML), Service de Neuropédiatrie

Paris, 75012, France

Location

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

Location

Related Publications (1)

• De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.

  PMID: 37624739 DERIVED

MeSH Terms

Conditions

Gangliosidosis, GM1; Lysosomal Storage Diseases

Condition Hierarchy (Ancestors)

Gangliosidoses; 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; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipidoses; Lipid Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Clinical Operations

  LYSOGENE

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2020
• First Posted: February 18, 2020
• Study Start: May 11, 2021
• Primary Completion: May 22, 2023
• Study Completion: May 22, 2023
• Last Updated: June 9, 2023

Record last verified: 2023-06

Locations

GB (1); US (1); FR (1)