Exploring a new gene therapy for infants with Type II Gaucher Disease

An Exploratory Clinical Trial to Evaluate the Tolerability and Safety of VGN-R08b Via Intracerebroventricular Injection in Patients With Type II Gaucher Disease

This study is testing a new gene therapy for infants with Type II Gaucher Disease to see if it is safe and helps improve their condition.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 0 Months to 24 Months
• Sex: All
• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine (Academic / other)
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT06272149 on ClinicalTrials.gov

What this trial studies

This exploratory trial aims to assess the safety and tolerability of VGN-R08b, a gene therapy designed to treat infants diagnosed with Type II Gaucher disease. The study involves a single-center, open-label design with a dose-climbing phase followed by a dose-expanding phase to gather preliminary evidence on the treatment's efficacy. Participants will receive injections of VGN-R08b directly into the cerebroventricular space, targeting the underlying genetic cause of the disease. The trial focuses on infants under 24 months with confirmed GBA1 mutations and neurological symptoms.

Who should consider this trial

Good fit: Ideal candidates are infants aged 24 months or younger with a confirmed diagnosis of Type II Gaucher disease and neurological symptoms.

Not a fit: Patients with significant CNS diseases unrelated to Gaucher disease or those with severe visceral symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly improve the quality of life and survival rates for infants with Type II Gaucher disease.

How similar studies have performed: While gene therapy approaches for metabolic disorders are being explored, this specific application for Type II Gaucher disease is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Infants with age of ≤24 months.
2. Historical diagnosis of Gaucher disease confirmed by GCase enzyme activity test, and with GBA1 biallelic mutations.
3. Neurological signs and/or symptoms consistent with diagnosis of GD2.
4. Parent(s)/legal guardian(s) of subject must give their consent for subject to enroll in the study.
5. 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.

Exclusion Criteria:

1. 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.
2. Achieved independent gait.
3. 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.
4. Clinically active infection (including HIV, HBV, HCV or syphilis).
5. For those receiving enzyme replacement therapy and/or substrate reduction therapy and/or ambroxol for Gaucher disease, stable treatment ≤2 months before enrollment.
6. Use of strong inhibitors or inducers of cytochrome CYP3A4 or P-glycoprotein (P-gp) medications, herbals, or over-the-counter agents.
7. Any type of prior gene or cell therapy.
8. Immunizations (live vaccines) in the prior 4 weeks.
9. Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified (topical preparations for dermatological conditions are allowed).
10. Patients with anti-AAV9 neutralizing antibody titer over 1:5.
11. Brain MRI (magnetic resonance imaging) showing clinically significant abnormality considered to prevent intracisternal injection.
12. Contraindication to sedation during surgery or imaging studies (PET).
13. 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.

Where this trial is running

Shanghai, Shanghai Municipality

• Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Principal investigator: Zhang Huiwen, Dr. — Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Study coordinator: Zhang Huiwen, Dr.

Conditions Type II Gaucher Disease; GBA, Glucocerceramide, AAV9, CNS gene therapy