A Study to Evaluate the Tolerability, Safety and Efficacy of VGM-R02b

Plain-language summary

This Phase 1, open-label, single-arm, single-dose trial evaluates the gene replacement therapy VGM-R02b (rAAV9-GCDH) in patients with Glutaric Acidemia Type I (GA-I) confirmed genetically by biallelic GCDH mutation. In the dose-escalation part, 1 to 3 patients aged 6 years or younger at screening are enrolled per dose group, while the dose-expansion sample size will be calculated and adjusted based on the escalation efficacy and safety data. Participants must have one of the obvious disease-related neurological manifestations, such as macrocephaly, at screening.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

Phase 1

Status

Recruiting

Sponsor

Shanghai Vitalgen BioPharma Co., Ltd.

Intervention

VGM-R02b (rAAV9-GCDH)

Start date

4/29/2024

Estimated completion

8/1/2027

Countries

China

Locations

• Hangzhou, China

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

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.