An Exploratory Clinical Trial of VGN-R08b in Patients With Type II Gaucher Disease

NCT06272149 | Recruiting Early Phase 1 DMC

• 1 other identifier: VGN-R08b-001
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This exploratory trial is to prove the tolerability and safety of VGN-R08b to treat infants with type II Gaucher disease.

Conditions

Type II Gaucher Disease

Keywords

GBA, Glucocerceramide, AAV9, CNS gene therapy

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events (AEs), Serious Adverse Events (SAEs)

  Adverse Events (AEs), Serious Adverse Events (SAEs)

  Week 52

Secondary Outcomes (7)

• Long-term safety follow-up

  Up to Year 5

• Survival ratio at age of 24 months

  Baseline until event, or reach the age of 24 months, Up to Year 5

• Changes in the activity of glucose cerebroside lipase (GCase)

  Up to Year 5

• Changes in the activity of glucose cerebroside (GC) levels

  Up to Year 5

• Changes in the activity of glucose sphingosine (Lyso GL1) levels in peripheral blood and CSF after medication

  Up to Year 5

Study Arms (1)

type II Gaucher disease

EXPERIMENTAL

This is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2\~4 subjects in dose-expanding phase

Drug: VGN-R08b

Interventions

VGN-R08b DRUG

VGN-R08b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human GBA1 being injected directly into intracerebroventricular.

type II Gaucher disease

Eligibility Criteria

• Age: 0 Months - 24 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Infants with age of ≤24 months.
• Historical diagnosis of Gaucher disease confirmed by GCase enzyme activity test, and with GBA1 biallelic mutations.
• Neurological signs and/or symptoms consistent with diagnosis of GD2.
• Parent(s)/legal guardian(s) of subject must give their consent for subject to enroll in the study.
• Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.

You may not qualify if:

• Diagnosis of a significant CNS disease other than GD2 that may be a cause for the patient's GD symptoms or may confound study objectives.
• Achieved independent gait.
• Severe visceral symptoms of GD which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
• Clinically active infection (including HIV, HBV, HCV or syphilis).
• For those receiving enzyme replacement therapy and/or substrate reduction therapy and/or ambroxol for Gaucher disease, stable treatment ≤2 months before enrollment.
• Use of strong inhibitors or inducers of cytochrome CYP3A4 or P-glycoprotein (P-gp) medications, herbals, or over-the-counter agents.
• Any type of prior gene or cell therapy.
• Immunizations (live vaccines) in the prior 4 weeks.
• Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified (topical preparations for dermatological conditions are allowed).
• Patients with anti-AAV9 neutralizing antibody titer over 1:5.
• Brain MRI (magnetic resonance imaging) showing clinically significant abnormality considered to prevent intracisternal injection.
• Contraindication to sedation during surgery or imaging studies (PET).
• Presence of other significant medical conditions that would create an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.

Sponsors & Collaborators

• Xinhua Hospital, Shanghai Jiao Tong University School of Medicine: lead
• Shanghai Vitalgen BioPharma Co., Ltd.: collaborator

Study Sites (1)

Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200097, China

RECRUITING

MeSH Terms

Conditions

Gaucher Disease

Condition Hierarchy (Ancestors)

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; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Lipid Metabolism Disorders

Study Officials

• Zhang Huiwen, Dr.

  Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhang Huiwen, Dr.

CONTACT

18117165075; zhanghuiwen@xinhuamed.com.cn

Study Design

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

Study Record Dates

• First Submitted: July 17, 2023
• First Posted: February 22, 2024
• Study Start: March 1, 2023
• Primary Completion: January 15, 2025
• Study Completion (Estimated): February 28, 2029
• Last Updated: February 22, 2024

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)