Type II Gaucher DiseaseEarly Phase 1NCT06272149
An Exploratory Clinical Trial of VGN-R08b in Patients With Type II Gaucher Disease
A Early Phase 1 study testing VGN-R08b in people with Type II Gaucher Disease, run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
This exploratory trial is to prove the tolerability and safety of VGN-R08b to treat infants with type II Gaucher disease. Read more about this study
- Who is it for?
- Ages 0 to 24 months
- Conditions the study is for
- Type II Gaucher Disease
- What is being tested?
- VGN-R08b
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2023to 28 Feb 2029
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 0 to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Infants with age of ≤24 months.
- Historical diagnosis of Gaucher disease confirmed by GCase enzyme activity test, and with GBA1 biallelic mutations.
- Neurological signs and/or symptoms consistent with diagnosis of GD2.
- Parent(s)/legal guardian(s) of subject must give their consent for subject to enroll in the study.
- Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.
Who cannot join
- Diagnosis of a significant CNS disease other than GD2 that may be a cause for the patient's GD symptoms or may confound study objectives.
- Achieved independent gait.
- Severe visceral symptoms of GD which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
- Clinically active infection (including HIV, HBV, HCV or syphilis).
- For those receiving enzyme replacement therapy and/or substrate reduction therapy and/or ambroxol for Gaucher disease, stable treatment ≤2 months before enrollment.
- Use of strong inhibitors or inducers of cytochrome CYP3A4 or P-glycoprotein (P-gp) medications, herbals, or over-the-counter agents.
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- Any type of prior gene or cell therapy.
- Immunizations (live vaccines) in the prior 4 weeks.
- Use of systemic immunosuppressant or corticosteroid therapy other than protocol-specified (topical preparations for dermatological conditions are allowed).
- Patients with anti-AAV9 neutralizing antibody titer over 1:5.
- Brain MRI (magnetic resonance imaging) showing clinically significant abnormality considered to prevent intracisternal injection.
- Contraindication to sedation during surgery or imaging studies (PET).
- Presence of other significant medical conditions that would create an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200097
Zhang Huiwen, Dr., 18117165075, zhanghuiwen@xinhuamed.com.cn
About this study
Official title: An Exploratory Clinical Trial to Evaluate the Tolerability and Safety of VGN-R08b Via Intracerebroventricular Injection in Patients With Type II Gaucher Disease
This exploratory trial is to prove the tolerability and safety of VGN-R08b to treat infants with type II Gaucher disease.
Read the detailed description
Gaucher disease (GD) is an autosomal recessive genetic metabolic disorder. Due to the mutation of Glucocerebrosidase gene (GBA1), the activity of glucocerebrosidase (GCase) in the lysosome of the body is reduced, causing its substrate glucocerceramide to be accumulated in macrophage lysosomes in the liver, spleen, bone, lung, brain and eyes. Type II, acute neuropathy, with extensive and severe visceral involvement, usually develops within the first year of life, and most children die before the age of 2. VGN-R08b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human GBA1 being injected directly into intracerebroventricular.
This is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2~4 subjects in dose-expanding phase.
This study is to give preliminary evidence for the safety and efficacy of VGN-R08b treatment for patients with type II Gaucher disease.
- Conditions
- Type II Gaucher Disease
- Being tested
- VGN-R08b
- Keywords
- GBA, Glucocerceramide, AAV9, CNS gene therapy
- Medical subject headings
- Gaucher Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VGN-R08bDrug
VGN-R08b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human GBA1 being injected directly into intracerebroventricular.
| Study group | Role | What they receive |
|---|---|---|
| type II Gaucher disease | Experimental | This is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2~4 subjects in dose-expanding phase Receives: Drug: VGN-R08b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Adverse Events (AEs), Serious Adverse Events (SAEs)
Measured: Week 52
Secondary outcomes (7)
Long-term safety follow-up
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Measured: Up to Year 5
Survival ratio at age of 24 months
Survival ratio at age of 24 months
Measured: Baseline until event, or reach the age of 24 months, Up to Year 5
Changes in the activity of glucose cerebroside lipase (GCase)
Pharmacodynamic indicators
Measured: Up to Year 5
Changes in the activity of glucose cerebroside (GC) levels
Pharmacodynamic indicators
Measured: Up to Year 5
Changes in the activity of glucose sphingosine (Lyso GL1) levels in peripheral blood and CSF after medication
Pharmacodynamic indicators
Measured: Up to Year 5
Immunogenicity
Number of subjects producing antibodies against AAV9 and GCase
Measured: 26 weeks
Changes in the genomic level of VGN-R08b vector in peripheral blood after medication
Pharmacokinetics
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Feb 2024
- Study start1 Mar 2023
- Primary completion15 Jan 2025 (estimated)
- Study completion28 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type II Gaucher DiseaseStudies of the same condition, open and under way.
- More trials run by Xinhua Hospital, Shanghai Jiao Tong University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Vitalgen BioPharma Co., Ltd.
- Responsible party
- Sponsor
- Investigators
- Zhang Huiwen, Dr., Principal investigator, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06272149
- Sponsor's protocol ID
- VGN-R08b-001
- Status last verified
- Feb 2023
- First submitted
- 17 Jul 2023
- Last updated
- 22 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Trial to Evaluate the Tolerability and Safety of VGN-R08b Via Intracerebroventricular Injection in Patients With Type II Gaucher Disease
- ClinicalTrials.gov ID
- NCT06272149
- Acronym / sponsor ID
- VGN-R08b-001
- Conditions
- Type II Gaucher Disease
- Keywords
- GBA, Glucocerceramide, AAV9, CNS gene therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Xinhua Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Collaborators
- Shanghai Vitalgen BioPharma Co., Ltd.
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 15 Jan 2025 (estimated)
- Study completion
- 28 Feb 2029 (estimated)
- First posted
- 22 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This exploratory trial is to prove the tolerability and safety of VGN-R08b to treat infants with type II Gaucher disease.
Detailed description
Gaucher disease (GD) is an autosomal recessive genetic metabolic disorder. Due to the mutation of Glucocerebrosidase gene (GBA1), the activity of glucocerebrosidase (GCase) in the lysosome of the body is reduced, causing its substrate glucocerceramide to be accumulated in macrophage lysosomes in the liver, spleen, bone, lung, brain and eyes. Type II, acute neuropathy, with extensive and severe visceral involvement, usually develops within the first year of life, and most children die before the age of 2. VGN-R08b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human GBA1 being injected directly into intracerebroventricular.
This is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2~4 subjects in dose-expanding phase.
This study is to give preliminary evidence for the safety and efficacy of VGN-R08b treatment for patients with type II Gaucher disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| type II Gaucher disease | Experimental | Drug: VGN-R08bThis is a single-center, open, dose-climbing investigator-sponsored exploratory clinical study that included a dose-climbing phase and a dose-expanding phase. The sponsor plans to explore two dose levels in dose-climbing phase (one subject each cohort), then have additional 2~4 subjects in dose-expanding phase |
Who may qualify
- Ages
- 0 to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Infants with age of ≤24 months.
- Historical diagnosis of Gaucher disease confirmed by GCase enzyme activity test, and with GBA1 biallelic mutations.
- Neurological signs and/or symptoms consistent with diagnosis of GD2.
- Parent(s)/legal guardian(s) of subject must give their consent for subject to enroll in the study.
- Parent(s)/legal guardian(s) of the subject must agree to comply with the requirements of the study, including providing disease information and support disease assessment of symptoms.
Key exclusion criteria (13 listed)
- Diagnosis of a significant CNS disease other than GD2 that may be a cause for the patient's GD symptoms or may confound study objectives.
- Achieved independent gait.
- Severe visceral symptoms of GD which, in the opinion of the Investigator, would pose an unacceptable risk to the patient or interfere with the patient's ability to comply with study procedures or interfere with the conduct of the study.
- Clinically active infection (including HIV, HBV, HCV or syphilis).
- For those receiving enzyme replacement therapy and/or substrate reduction therapy and/or ambroxol for Gaucher disease, stable treatment ≤2 months before enrollment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VGN-R08bVGN-R08b is a kind of Gene therapy with adeno-associated virus (AAV) serotype 9 (AAV9) driven human GBA1 being injected directly into intracerebroventricular. | Drug | type II Gaucher disease |
Primary outcome
Number of Adverse Events (AEs), Serious Adverse Events (SAEs)
Time frame: Week 52
Adverse Events (AEs), Serious Adverse Events (SAEs)
7 secondary outcomes
Long-term safety follow-up
Time frame: Up to Year 5
Survival ratio at age of 24 months
Time frame: Baseline until event, or reach the age of 24 months, Up to Year 5
Changes in the activity of glucose cerebroside lipase (GCase)
Time frame: Up to Year 5
Changes in the activity of glucose cerebroside (GC) levels
Time frame: Up to Year 5
Changes in the activity of glucose sphingosine (Lyso GL1) levels in peripheral blood and CSF after medication
Time frame: Up to Year 5
Immunogenicity
Time frame: 26 weeks
Changes in the genomic level of VGN-R08b vector in peripheral blood after medication
Time frame: 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhang Huiwen, Dr. principal investigator
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing VGN-R08b in people with Type II Gaucher Disease, run by Xinhua Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhang Huiwen, Dr. (18117165075, zhanghuiwen@xinhuamed.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Adverse Events (AEs), Serious Adverse Events (SAEs) (time frame: Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2024.