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

Lysogene

Status and phase

Terminated

Phase 2

Phase 1

Conditions

GM1 Gangliosidosis

Treatments

Genetic: LYS-GM101

Study type

Interventional

Funder types

Industry

Identifiers

NCT04273269

P1-GM-101

Details and patient eligibility

About

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.

Full description

GM1 gangliosidosis is a fatal autosomal recessive disease caused by mutations in the GLB1 gene leading to accumulation of GM1 ganglioside in neurons and progressive neurodegeneration. There are three pediatric subtypes: early infantile, late infantile and juvenile. This is an interventional, multicenter, single-arm, 2-stage adaptive design study of LYS-GM101 for which the first stage (Stage 1) is for safety evaluation (FIH) and the second stage (Stage 2) will establish efficacy as compared to the natural history of the disease. The participants with infantile GM1 gangliosidosis will receive a single dose of LYS-GM101 by intracisternal injection. After a two-year evaluation period (main part of the study), each participant will be followed for an additional three-year long-term follow-up period.

Enrollment

5 patients

Sex

All

Ages

Under 3 years old

Volunteers

No Healthy Volunteers

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

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 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