Evaluating a new gene therapy for Glutaric Acidemia Type I

An Open-Label, Dose-Escalation and Dose-Expansion Phase I Clinical Study to Evaluate the Tolerability, Safety and Efficacy of VGM-R02b in Patients With Glutaric Acidemia Type I

This study is testing a new gene therapy for young patients with Glutaric Acidemia Type I to see if it is safe and can help improve their condition.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: N/A to 6 Years
• Sex: All
• Sponsor: Shanghai Vitalgen BioPharma Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06217861 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial is an open-label, single-arm, single-dose evaluation of VGM-R02b, a gene replacement therapy, in young patients diagnosed with Glutaric Acidemia Type I (GA-I) confirmed by GCDH gene mutation. The trial involves a screening period to determine eligibility, followed by surgical administration of the therapy via an Ommaya fluid reservoir or intra-cerebroventricular injection. Patients will be monitored postoperatively for safety and efficacy over a period of up to 52 weeks. The study aims to assess the tolerability and potential benefits of this innovative treatment approach.

Who should consider this trial

Good fit: Ideal candidates are children aged 6 years or younger with a confirmed diagnosis of GA-I and specific neurological manifestations.

Not a fit: Patients with recurrent seizures unsuitable for surgery or severe comorbid conditions may not benefit from this therapy.

Why it matters

Potential benefit: If successful, this therapy could significantly improve neurological outcomes and quality of life for children with Glutaric Acidemia Type I.

How similar studies have performed: While gene therapy approaches are emerging, this specific intervention is novel and has not been extensively tested in similar populations.

Eligibility criteria

Inclusion Criteria:

1. Subjects must be ≤ 6 years;
2. History of diagnosis of GA-I, and confirmed by gene mutation analysis with biallelic GCDH mutation;
3. At the time of screening, there was one of the obvious neurological manifestations associated with the following diseases, including macrocephaly, dystonia, and motor/intellectual development Poor fertility, epilepsy, abnormal EEG;
4. Those who are receiving standard treatment recommended by the guidelines and whose symptoms remain poorly controlled by the investigator;
5. Plasma GA and 3-OHGA levels were higher than the normal range during screening;

Exclusion Criteria:

1. Participation in gene therapy or stem cell transduction therapy at any time prior to screening for this trial or participation in any other clinical trial within 3 months prior to screening;
2. Recurrent seizures that are not suitable for surgery, based on Investigator judgment;
3. Current severe liver or kidney or cardiovascular disease or coagulation dysfunction, autoimmune deficiency, or uncontrolled autoimmune disease or need immunosuppressive long-term treatment, poorly controlled diabetes (HBA1C ≥7% at screening) or high blood pressure;
4. Active viral infection (includes HIV or serology positive for hepatitis B or C or syphilis);
5. Presence or history of malignancy;
6. Received systemic immunosuppressive therapy within 3 months prior to screening;
7. Received vaccine within 4 weeks prior to administration or plan to receive vaccine within 1 year after administration;
8. Plan to receive surgery during the study;
9. Current using medications including, drugs, herbal or OTC medications that strongly inhibit or induce CYP3A4 or P-glycoprotein (P-gp), e.g., metoclopramide, grapefruit juice, ketoconazole, erythromycin;
10. Abnormal brain structure, not suitable for lateral ventricle administration;
11. Abnormal laboratory test results, which are judged by the investigator not suitable for surgery;
12. History of systemic hypersensitivity reaction to investigational product, the excipients contained in the formulation, or prophylactic immunosuppressant;
13. Contraindicated use of corticosteroids and sirolimus;
14. Contraindicated with general anesthesia or sedation;
15. As judged by the investigator, unable to perform lateral ventricle puncture or Ommaya capsule implantation or lumbar puncture;
16. Unable to perform CT or MRI;
17. Poor compliance;
18. Any other situation where, judged by the investigator, the subject is not suitable for participating in this study.

Where this trial is running

Hangzhou, Zhejiang

• The Children's Hospital Zhejiang University Shcool of Medicine — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Qiang Shu — The Children's Hospital of Zhejiang University School of Medicine
• Study coordinator: Xianfeng Wang

Conditions Glutaric Acidemia Type I; Glutaric Aciduria Type I; AAV; gene therapy; ICV; GCDH