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

NCT06217861 | Recruiting Phase 1

• 2 other identifiers: VGM-R02b-1012023LP01348
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Glutaric Acidemia Type I; Glutaric Aciduria Type I

Keywords

AAV; gene therapy; ICV; GCDH

Outcome Measures

Primary Outcomes (2)

• The incidence and severity of AEs and SAEs

  An AE is any untoward medical occurrence (eg any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product.

  up to 52 weeks

• Evaluate changes from baseline in vital signs, and clinical laboratory results

  Clinically significant abnormal laboratory values or test results must be identified through a review of values outside of normal ranges/clinically notable ranges, significant changes from baseline or the previous visit, or values which are considered to be non-typical in participant with the underlying disease.

  up to 52 weeks

Secondary Outcomes (6)

• Changes in Barry Albright Dystonia Scale from baseline.

  up to 52 weeks

• Changes in Peabody Developmental Motor Scale (PDMS-2) from baseline.

  up to 52 weeks

• Changes in Bayley Scales of Infant and Toddler Development (BSID) or Wechsler Preschool and Primary Scale of Intelligence (WPPSI) from baseline.

  up to 52 weeks

• Neuroimaging.

  up to 52 weeks

• Biomarkers.

  up to 52 weeks

Study Arms (1)

VGM-R02b

EXPERIMENTAL

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

Biological: VGM-R02b

Interventions

VGM-R02b BIOLOGICAL

Administered as specified in the treatment arm.

Also known as: rAAV9-GCDH

VGM-R02b

Eligibility Criteria

• Age: Up to 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects must be ≤ 6 years;
• History of diagnosis of GA-I, and confirmed by gene mutation analysis with biallelic GCDH mutation;
• 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;
• Those who are receiving standard treatment recommended by the guidelines and whose symptoms remain poorly controlled by the investigator;
• Plasma GA and 3-OHGA levels were higher than the normal range during screening;

You may not qualify if:

• 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;
• Recurrent seizures that are not suitable for surgery, based on Investigator judgment;
• 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;
• Active viral infection (includes HIV or serology positive for hepatitis B or C or syphilis);
• Presence or history of malignancy;
• Received systemic immunosuppressive therapy within 3 months prior to screening;
• Received vaccine within 4 weeks prior to administration or plan to receive vaccine within 1 year after administration;
• Plan to receive surgery during the study;
• 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;
• Abnormal brain structure, not suitable for lateral ventricle administration;
• Abnormal laboratory test results, which are judged by the investigator not suitable for surgery;
• History of systemic hypersensitivity reaction to investigational product, the excipients contained in the formulation, or prophylactic immunosuppressant;
• Contraindicated use of corticosteroids and sirolimus;
• Contraindicated with general anesthesia or sedation;
• As judged by the investigator, unable to perform lateral ventricle puncture or Ommaya capsule implantation or lumbar puncture;

Sponsors & Collaborators

• Shanghai Vitalgen BioPharma Co., Ltd.: lead

Study Sites (1)

The Children's Hospital Zhejiang University Shcool of Medicine

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Glutaric Acidemia I

Study Officials

• Qiang Shu

  The Children's Hospital Zhejiang University Shcool of Medicine

  PRINCIPAL INVESTIGATOR

• Rulai Yang

  The Children's Hospital Zhejiang University Shcool of Medicine

  PRINCIPAL INVESTIGATOR

• Guanping Dong

  The Children's Hospital Zhejiang University Shcool of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xianfeng Wang

CONTACT

18816250806; xianfeng.wang@vitalgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2023
• First Posted: January 23, 2024
• Study Start: April 29, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 17, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)