- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06217861
A Study to Evaluate the Tolerability, Safety and Efficacy of VGM-R02b
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Xianfeng Wang
- Phone Number: 18816250806
- Email: xianfeng.wang@vitalgen.com
Study Locations
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Shanghai
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Shanghai, Shanghai, China
- Shanghai Vitalgen Biopharma Co.,Ltd.
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Contact:
- Xianfeng Wang
- Phone Number: 18816250806
- Email: xianfeng.wang@vitalgen.com
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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;
Exclusion Criteria:
- 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;
- Unable to perform CT or MRI;
- Poor compliance;
- Any other situation where, judged by the investigator, the subject is not suitable for participating in this study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: VGM-R02b
VGM-R02b is an adeno-associated viral vector 9 delivering human Glutaryl-CoA Dehydrogenase (GCDH) gene.
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Administered as specified in the treatment arm.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The incidence and severity of AEs and SAEs
Time Frame: up to 52 weeks
|
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.
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up to 52 weeks
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Evaluate changes from baseline in vital signs, and clinical laboratory results
Time Frame: up to 52 weeks
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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.
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up to 52 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Barry Albright Dystonia Scale from baseline.
Time Frame: up to 52 weeks
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The BAD Scale is a 5-point, criterion-based, ordinal scale designed to assess dystonia in eight body regions: eyes, mouth, neck, trunk, and the four extremities.
Raters score dystonia as none (0), slight (1), mild (2), moderate (3), or severe (4).
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up to 52 weeks
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Changes in Peabody Developmental Motor Scale (PDMS-2) from baseline.
Time Frame: up to 52 weeks
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The Peabody Developmental Motor Scales, a norm referenced tool commonly used to assess infants' fine and gross motor development, also is widely used for children of preschool age.
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up to 52 weeks
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Changes in Bayley Scales of Infant and Toddler Development (BSID) or Wechsler Preschool and Primary Scale of Intelligence (WPPSI) from baseline.
Time Frame: up to 52 weeks
|
BSID is an extensive formal developmental assessment tool for diagnosing developmental delays in early childhood, this will be used in 1~42 month patients. The WPPSI uses subtests to determine a child's Verbal and Performance IQ scores as well as the processing speed for children ages over 42 months. |
up to 52 weeks
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Neuroimaging.
Time Frame: up to 52 weeks
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Changes in clinically significant abnormalities on brain MRI and MRS compared to Baseline.
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up to 52 weeks
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Biomarkers.
Time Frame: up to 52 weeks
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Changes of C5DC GA, 3-OHGA in CSF and plasma.
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up to 52 weeks
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Immunogenicity.
Time Frame: up to 52 weeks
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The antibody titer and the number of subjects with positive anti-AAV9 and anti-hGCDH antibodiesin the blood and CSF. The antibody titer and the number of subjects with positive anti-AAV9 and anti-hGCDH specific T cell immune response of peripheral blood mononuclear cells (PBMC). |
up to 52 weeks
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Collaborators and Investigators
Investigators
- Principal Investigator: 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
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- VGM-R02b-101
- 2023LP01348 (Other Identifier: CDE)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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