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

NCT ID: NCT06217861

Last Updated: 2024-05-17

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-04-29
• Study Completion Date: 2026-08-31

Brief Summary

Phase I, open-label, single-arm, single-dose, trial of VGM-R02b (gene replacement therapy) in patients with Glutaric Acidemia Type I (GA-I) who meet enrollment criteria and are genetically confirmed by GCDH gene mutation. 1 to 3 patients aged≤ 6 years at the time of screening will be enrolled in each dose group in the dose escalation part. In the dose expansion part, the sample size will be statistically calculated and adjusted according to the efficacy and safety data in the dose escalation part.

Detailed Description

This study consists of screening period, treatment period and postoperative monitoring period and follow-up period. During the screening period (Days -28 to -1), patients whose parent(s)/legal guardian(s) provide informed consent will complete screening procedures to determine eligibility for trial enrollment. Eligible subjects will be admitted to the clinical research center before surgical administration to complete the preoperative examination and determine the surgical plan. Ommaya fluid reservoir capsule implantation will be used in this study (if there were problems with Ommaya implantation, intra-cerebroventricular injection could also be used for drug administration). The day of administration set to be D1. Prophylactic immunosuppressive therapy including Methylprednisolone, Prednisolone and Rapamycin was initiated on D1. Then all the examinations during the 7-day postoperative observation period will be completed based on the evaluation time point specified in the Schedule of Assessments table. Subjects may be discharged 7 days after the infusion, based on Investigator judgment. During the outpatient follow-up period (up to 52 weeks after administration), subjects will return at regularly scheduled intervals for efficacy and safety assessments until the End of Trial. After the End of Trial visit, eligible patients will be asked to participate into the long-term follow up trial.

Conditions

Glutaric Acidemia Type I; Glutaric Aciduria Type I

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

VGM-R02b

VGM-R02b is an adeno-associated viral vector 9 delivering human Glutaryl-CoA Dehydrogenase (GCDH) gene.

Group Type: EXPERIMENTAL

VGM-R02b

Intervention Type: BIOLOGICAL

Administered as specified in the treatment arm.

Interventions

VGM-R02b

Administered as specified in the treatment arm.

Intervention Type: BIOLOGICAL

Other Intervention Names

rAAV9-GCDH

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.

• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Vitalgen BioPharma Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Qiang Shu

Role: PRINCIPAL_INVESTIGATOR

The Children's Hospital Zhejiang University Shcool of Medicine

Rulai Yang

Role: PRINCIPAL_INVESTIGATOR

The Children's Hospital Zhejiang University Shcool of Medicine

Guanping Dong

Role: PRINCIPAL_INVESTIGATOR

The Children's Hospital Zhejiang University Shcool of Medicine

Locations

The Children's Hospital Zhejiang University Shcool of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xianfeng Wang

Role: CONTACT

xianfeng.wang@vitalgen.com

18816250806

Facility Contacts

Xianfeng Wang

Role: primary

xianfeng.wang@vitalgen.com

18816250806

Other Identifiers

2023LP01348

Identifier Type: OTHER

Identifier Source: secondary_id

VGM-R02b-101

Identifier Type: -

Identifier Source: org_study_id