NCT06199531

Safety and Efficacy of GS-100 Gene Therapy in Patients With NGLY1 Deficiency

A Phase 1/2/3 Open-label, Single Arm, Dose-finding Study to Investigate Long-term Safety, Tolerability and Efficacy of GS-100, an Adeno-associated Virus Serotype 9 (AAV9) Vector-mediated Gene Transfer of Human NGLY1, in Patients With NGLY1 Deficiency

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Grace Science, LLC · Industry
• Sex: All
• Age: 2 Years – 18 Years
• Healthy volunteers: Not accepted

Summary

A non-randomized, open-label, dose escalation study of a single intracerebroventricular (ICV) administration of a gene replacement therapy in subjects who are 2 to 18 years old with NGLY1 Deficiency.

Detailed description

This study is a first in human (FIH) open-label, dose escalation study designed to assess the safety and efficacy of administration of an adeno-associated viral vector serotype 9 (AAV9) carrying the gene encoding N-glycanase 1 (NGLY1) in subjects with NGLY1 Deficiency. The study treatment will be delivered via intracerebroventricular (ICV) injection. All outcomes (primary, secondary, exploratory) will be assessed at 52 weeks. Safety will be monitored continuously throughout the study for adverse / serious adverse events and dose limiting toxicities. Efficacy outcomes will be assessed at baseline and 52 weeks. The co-primary outcomes will be change from baseline in cerebrospinal fluid (CSF) GlcNAc-Asn (GNA, or N-acetylglucosamine), the NGLY1 Deficiency biomarker, and change in motor subdomain on the Bayley Scales of Infant and Toddler Development (BSID-4). Secondary outcomes will include weight (Z-score), clinical and caregiver impressions of change, and other neurocognitive assessment tools. Exploratory outcomes will include brain volumes as measured by magnetic resonance imaging (MRI), quality of life assessments (including sleep habits), liver function test results, and lacrimation assessments. Each participant will be followed for safety and efficacy for 5 years after treatment.

Conditions

• NGLY1 Deficiency

Interventions

Type	Name	Description
GENETIC	GS-100	A single intracerebroventricular (ICV) dose of the study treatment will be administered to patients with confirmed mutations in the NGLY1 gene.

Timeline

• Start date: 2024-02-13
• Primary completion: 2028-01-31
• Completion: 2028-01-31
• First posted: 2024-01-10
• Last updated: 2025-04-24

Locations

3 sites across 1 country: United States

Regulatory

• FDA-regulated drug study