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

Last updated: May 17, 2024
Sponsor: Shanghai Vitalgen BioPharma Co., Ltd.
Overall Status: Active - Recruiting

Phase

1

Condition

Phenylketonuria

Treatment

VGM-R02b

Clinical Study ID

NCT06217861
VGM-R02b-101
2023LP01348
  • Ages < 6
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Subjects must be ≤ 6 years;

  2. History of diagnosis of GA-I, and confirmed by gene mutation analysis with biallelicGCDH mutation;

  3. At the time of screening, there was one of the obvious neurological manifestationsassociated with the following diseases, including macrocephaly, dystonia, andmotor/intellectual development Poor fertility, epilepsy, abnormal EEG;

  4. Those who are receiving standard treatment recommended by the guidelines and whosesymptoms remain poorly controlled by the investigator;

  5. Plasma GA and 3-OHGA levels were higher than the normal range during screening;

Exclusion

Exclusion Criteria:

  1. Participation in gene therapy or stem cell transduction therapy at any time prior toscreening for this trial or participation in any other clinical trial within 3months prior to screening;

  2. Recurrent seizures that are not suitable for surgery, based on Investigatorjudgment;

  3. Current severe liver or kidney or cardiovascular disease or coagulation dysfunction,autoimmune deficiency, or uncontrolled autoimmune disease or need immunosuppressivelong-term treatment, poorly controlled diabetes (HBA1C ≥7% at screening) or highblood pressure;

  4. Active viral infection (includes HIV or serology positive for hepatitis B or C orsyphilis);

  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 vaccinewithin 1 year after administration;

  8. Plan to receive surgery during the study;

  9. Current using medications including, drugs, herbal or OTC medications that stronglyinhibit or induce CYP3A4 or P-glycoprotein (P-gp), e.g., metoclopramide, grapefruitjuice, ketoconazole, erythromycin;

  10. Abnormal brain structure, not suitable for lateral ventricle administration;

  11. Abnormal laboratory test results, which are judged by the investigator not suitablefor surgery;

  12. History of systemic hypersensitivity reaction to investigational product, theexcipients 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 orOmmaya 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 suitablefor participating in this study.

Study Design

Total Participants: 12
Treatment Group(s): 1
Primary Treatment: VGM-R02b
Phase: 1
Study Start date:
April 29, 2024
Estimated Completion Date:
August 31, 2026

Study 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.

Connect with a study center

  • Shanghai Vitalgen Biopharma Co.,Ltd.

    Shanghai, Shanghai
    China

    Site Not Available

  • The Children's Hospital Zhejiang University Shcool of Medicine

    Hangzhou, Zhejiang
    China

    Active - Recruiting

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