A Phase I/II Clinical Study to Evaluate the Safety and Efficacy of VGN-R08b in Patients With Type III Gaucher's Disease

A Phase I/II Clinical Study to Evaluate the Tolerance, Safety and Efficacy of VGN-R08b Intracerebroventricular Injection in Patients With Type III Gaucher's Disease

A phase I/II clinical study to evaluate the tolerance, safety and efficacy of VGN-R08b intracerebroventricular injection in patients with type III Gaucher's disease

Study Overview

• Status: Not yet recruiting
• Conditions: Gaucher Disease Type 3
• Intervention / Treatment: Drug: VGN-R08b; Drug: VGN-R08b; Drug: VGN-R08b

Detailed Description

This is an open-label, dose-escalation clinical trial, consisting of dose escalation and dose expansion. A total of 12 subjects are expected to be enrolled.

Dose escalation: Initially, three doses of 6×10^10 vg/g, 1.2×10^11 vg/g, and 1.8×10^11 vg/g (per unit brain weight) are planned to be explored . Three subjects will be enrolled in each dose group. The second and third subjects in the same dose group must be confirmed to be safe and tolerable after at least a 4-week safety assessment of the first subject before receiving the drug. For the high-dose group (1.8×10^11 vg/g), subjects will be enrolled one by one.

Dose expansion: After the dose escalation is completed, the SRC will comprehensively evaluate the data on efficacy, safety, and immunogenicity, etc., to select the optimal effective dose and expand the enrollment by 3 cases.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The signing of the informed consent form should be completed when the subject is at least 2 years old but less than 18 years old.
2. The subject has a documented medical history of Gaucher disease confirmed by GCase enzyme activity testing, and has a double GBA1 gene mutation.
3. According to the investigator's assessment, the neurological signs and/or symptoms are consistent with type III Gaucher disease.
4. At the time of enrollment, the subject has horizontal eye movement disorders (including gaze paralysis, or delayed or absent saccades), but there is no severe motor dysfunction resulting in bedridden status.
5. The subject is currently receiving substrate reduction therapy (SRT) and/or high-dose ambroxol for Gaucher disease treatment. The subject is required to have been on stable treatment for at least 2 months before enrollment and the investigator determines that the treatment is ineffective for neurological symptoms, or is willing to discontinue the treatment at the time of enrollment (discontinuation 1 week before administration).
6. The subject is currently receiving and willing to continue stable peripheral treatment (including imiglucerase or other ERT, or SRT), and the peripheral symptoms of Gaucher disease are stable at the time of screening, that is, all of the following conditions are met: hemoglobin level ≥ 11.0 g/dL (female) or ≥ 12.0 g/dL (male), platelet count ≥ 100×109/L, spleen volume < 10 times the normal value (MN), liver volume < 1.5 MN, and no bone crisis or asymptomatic bone disease (such as bone necrosis and/or pathological fractures causing bone pain) within 3 months before screening.
7. (Applicable) Male and female subjects with reproductive potential must continue to use an effective contraceptive method (including abstinence) correctly from the screening period until at least 1 year after the start of treatment, and not donate sperm or eggs.
8. The subject (applicable) and their parents/guardians must understand the trial information, purpose and risks described in the informed consent form, and authorize the use of the subject's health information and provide an informed consent form with the signature and date of signing.
9. The subject (applicable) and their parents/guardians are willing to participate in the study as information providers, providing the subject's health status, cognition and physical ability (including providing information for rating scales).

Exclusion Criteria:

1. There are other serious neurological disorders that may cause symptoms of Gaucher disease or interfere with the research objectives;
2. There are severe internal organ damages caused by Gaucher disease, which, after evaluation by the researchers, are considered to pose unacceptable risks to the subjects, or interfere with the subjects' research compliance, or interfere with the execution of the trial;
3. Long-term ventilation or long-term nasogastric feeding (long-term ventilation is defined as: requiring tracheotomy for respiratory assistance, or continuous 14 days or more of non-invasive respiratory assistance for ≥ 16 hours per day, excluding acute reversible diseases that require assisted ventilation and perioperative ventilation. Long-term nasogastric feeding refers to the use of a nasogastric tube for feeding due to severe loss of swallowing function);
4. There are severe immunodeficiencies or autoimmune diseases;

5. There is active infection (including viral infections such as HIV, HBV, HCV or syphilis);

   The following medication and treatment situations exist:

6. Currently using drugs, herbs, or over-the-counter medications that have strong inhibitory or inducing effects on CYP3A4 or P-gp;
7. Having received bone marrow or organ transplantation, or any gene or cell therapy;
8. Having undergone immunization (live vaccines) within 4 weeks;
9. Undergoing systemic immunosuppressive therapy or corticosteroid therapy other than that required by the protocol (local preparations for skin diseases can be used);

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose group (1); 3 subjects on 6×10^10 vg/g for at least 4 weeks post injection	Drug: VGN-R08b; 6×10^10 vg/g; Drug: VGN-R08b; 1.2×10^11 vg/g; Drug: VGN-R08b; 1.8×10^11 vg/g
Experimental: Dose group (2); 3 subjects on 1.2×10^11 vg/g for at least 4 weeks post injection	Drug: VGN-R08b; 6×10^10 vg/g; Drug: VGN-R08b; 1.2×10^11 vg/g; Drug: VGN-R08b; 1.8×10^11 vg/g
Experimental: Dose group (3); 3 subjects on 1.8×10^11 vg/g for at least 4 weeks post injection	Drug: VGN-R08b; 6×10^10 vg/g; Drug: VGN-R08b; 1.2×10^11 vg/g; Drug: VGN-R08b; 1.8×10^11 vg/g

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of adverse events (AE), Serious adverse events (SAE)	Vital signs, physical examination, laboratory test results will be monitored after drug injection	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Glucose Gangliosidase (GCase)	Changes in the activities of glucose gangliosidase (GCase) in peripheral blood and cerebrospinal fluid (CSF) after medication administration	Up to 5 years
Changes in Glucose sialic acid (Lyso-GL1)	Changes in the levels of glucose sialic acid (Lyso-GL1) in peripheral blood and cerebrospinal fluid (CSF) after medication administration	Up to 5 years
Changes in electrooculogram	Changes in pupillary reflex, horizontal eye movement and vertical eye movement after medication administration compared to the baseline	Up to 5 years
Changes in Scale for the Assessment and Rating of Ataxia	Changes in ataxia, and the proportion of subjects whose ataxia symptoms showed significant improvement compared to the baseline	Up to 5 years
Viral shedding	Changes in the genomic levels of the VGN-R08b vector in peripheral blood, urine, feces, and nasal mucosal secretions after medication administration	Up to 5 years
Immunogenicity	The number of subjects who produced antibodies against AAV9 and GCase, as well as the antibody titers, including in serum and CSF	Up to 5 years

Collaborators and Investigators

• Sponsor: Shanghai Vitalgen BioPharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 14, 2026
• Primary Completion (Estimated): May 29, 2028
• Study Completion (Estimated): August 16, 2032

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Lipid Metabolism Disorders; Lysosomal Storage Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Lipid Metabolism, Inborn Errors; Lysosomal Storage Diseases, Nervous System; Sphingolipidoses; Lipidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Gaucher Disease
• Other Study ID Numbers: VGN-R08b-102

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No