NCT04713475

Study of Safety, Tolerability and Efficacy of PBGM01 in Pediatric Participants With GM1 Gangliosidosis

Phase 1/2 Open-Label, Multicenter Study to Assess the Safety, Tolerability and Efficacy of a Single Dose of PBGM01 Delivered Into the Cisterna Magna of Pediatric Type 1 (Early Onset) and Type 2a (Late Onset) Infantile GM1 Gangliosidosis

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 26 (estimated)
• Sponsor: Gemma Biotherapeutics · Industry
• Sex: All
• Age: 1 Month – 24 Months
• Healthy volunteers: Not accepted

Summary

PBGM01 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the brain and peripheral tissues. This study will assess in a 2 part design the safety, tolerability and efficacy of PBGM01 in patients with early onset infantile (Type 1) and late onset infantile (Type 2a) GM1 gangliosidosis

Detailed description

GM1 gangliosidosis (GM1) is an autosomal recessive disorder that results from mutations in the galactosidase beta 1 gene (GLB1), which encodes beta-galactosidase (β-gal). β-gal is a lysosomal enzyme that catalyzes the first step in the degradation of GM1 ganglioside and keratan sulfate, and GM1 patients carry GLB1 alleles that produce little or no residual β-gal activity. PBGM01 is an adeno-associated viral vector serotype hu68 carrying GLB1, the gene encoding for human beta-galactosidase, formulated as a solution for injection into the cisterna magna. This is a global interventional, multicenter, single-arm, dose escalation, adaptive design study of PBGM01 delivered as a one-time dose administered into the cisterna magna to patients with early onset infantile (Type 1) and late onset infantile (Type 2a) GM1 gangliosidosis. In Part 1 of the study, the dose-escalation phase will assess three dose levels of PBGM01 as a one-time dose in six independent cohorts of patients with either Type 1 or Type 2a GM1 gangliosidosis. The cohorts for patients with Type 1 and Type 2a will be assessed independently from each other. Part 2 of the study will test the safety and efficacy of PBGM01 in confirmatory cohorts for Types 1 and Type 2a GM1 gangliosidosis with a dose chosen based on the data obtained in part 1 of the study. This will be a 2-year study with a 3-year safety extension.

Conditions

• GM1 Gangliosidosis
• GM1 Gangliosidosis, Type I
• GM1 Gangliosidosis, Type 2
• Beta-Galactosidase-1 (GLB1) Deficiency

Interventions

Type	Name	Description
BIOLOGICAL	PBGM01	AAVhu68 viral vector

Timeline

• Start date: 2021-03-17
• Primary completion: 2026-02-01
• Completion: 2029-02-01
• First posted: 2021-01-19
• Last updated: 2025-05-21

Locations

7 sites across 4 countries: United States, Brazil, Turkey (Türkiye), United Kingdom

Regulatory

• FDA-regulated drug study