Hemophilia BEarly Phase 1NCT05152732
Safety and Tolerability of VGB-R04 in Patients With Haemophilia B
A Early Phase 1 study testing VGB-R04 in people with Hemophilia B, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial summary
An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- VGB-R04
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteChina
- Study dates
- 28 Dec 2021to Dec 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 75 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male ≥18 years and ≤75years of age;
- Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%);
- At least 100 days exposure history to FIX;
- Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
- Have acceptable laboratory values:
- Hemoglobin ≥110 g/L;
Show all 13Show fewer
- Platelets ≥100×10'9 cells/L;
- AST, ALT, alkaline phosphatase ≤2×upper limit of normal (ULN) at the testing laboratory;
- Bilirubin ≤3× ULN ;
- Creatinine ≤1.5× ULN.
- No measurable factor IX inhibitor as assessed by the central laboratory and have no prior history of inhibitors to factor IX protein;
- Agree to use reliable barrier contraception until 3 consecutive samples are negative for vector sequences;
- Able to provide informed consent and comply with the requirements of the study.
Who cannot join
- Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to:
- Preexisting diagnosis of portal hypertension;
- Splenomegaly;
- Encephalopathy;
- Reduction of serum albumin;
- Evidence of significant liver fibrosis;
Show all 17Show fewer
- Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
- Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
- Evidence of active hepatitis B virus infection (HBV-DNA >103 IU/ml) or hepatitis C virus infection (HCV antigen and HCV-RNA positive);
- Evidence of malignant tumours or those with a previous history of malignant tumours;
- Have a history of chronic infection or other chronic diseases that the Investigator considers to constitute an unacceptable risk;
- Any immunodeficiency;
- Participated in a gene transfer trial within the last 52 weeks or in a clinical trial with an investigational drug within the last 4 weeks;
- Have used glucocorticoids, immunosuppressive drugs, or antipsychotics within the last 3 months;
- Previous history of hypersensitivity or allergic reaction to any FIX products or any immunoglobulin;
- Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
- Any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Blood diseases hospital
Tianjin, Tianjin Municipality, 300020
Lijun Liu, 00862223909095, liulijun@ihcams.ac.cn
About this study
An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B.
Read the detailed description
Hemophilia B is a genetic bleeding disorder caused by pathogenic variants (eg, mutations, deletion) in the FIX gene. HB patients have frequent and potentially life-threatening bleeding and often develop progressive physical disability and pain from chronic haemarthropathy. Current replacement therapy needs regular treatment in the life-long time, bringing heavy economic and social burdens.
VGB-R04 is a novel AAV vector carrying a high specific activity factor IX variant. This study is intended to evaluate the safety, tolerability and kinetics of a single IV infusion of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 6 weeks before administration of VGB-R04. All subjects will undergo 52(±2) weeks of safety observation and will be encouraged to enroll in an extension study to evaluate the long-term safety of VGB-R04 for a total of five years.
- Conditions
- Hemophilia B
- Being tested
- VGB-R04
- Keywords
- Hemophilia, AAV, safety, gene therapy
- Medical subject headings
- Hemophilia B, Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VGB-R04Genetic
A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant
| Study group | Role | What they receive |
|---|---|---|
| VGB-R04 | Experimental | Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer Receives: Genetic: VGB-R04 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.
Measured: Baseline up to Week 52
Incidence of serious adverse events
A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect
Measured: Baseline up to Week 52
Number of Participants with Clinically Significant Change from Baseline in Vital Signs
Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participants in the seated position, after having sat calmly for at least 5 minutes. The clinical significance of vital signs will be determined at the investigator's discretion
Measured: Baseline up to Week 52
Number of Participants with Clinically Significant Change From Baseline in Physical Examination Findings
The physical examination will include examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination will assess the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings will be considered to be clinically significant based on the investigator's decision
Measured: Baseline up to Week 52
Number of Participants with Clinical Laboratory Abnormalities
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings were considered to be clinically significant based on the investigator's decision.
Measured: Baseline up to Week 52
Secondary outcomes (6)
Vector- derived FIX:C Activity
All samples collected from participants for plasma FIX activity levels will be analyzed and used to determine peak and steady-state vector-derived circulating FIX activity levels
Measured: Baseline up to Week 52
Vector- derived FIX antigen levels
The vector-derived endogenous (not affected by intercurrent FIX product infusions) FIX:C activity antigen levels will be characterized by post-treatment population mean
Measured: Baseline up to Week 52
Annualized bleeding rate changes from baseline
The number of bleeding episodes per participant will be recorded, and the annualized number of bleeding episodes was calculated
Measured: Baseline up to Week 52
Annualized FIX consumption changes from baseline
The use of on-demand FIX replacement therapy will be recorded by dose (IU/kg) administered, and the annualized use of FIX replacement therapy will be calculated.
Measured: Baseline up to Week 52
Number of target joints
The criterion of the target joint is a minimum of three bleeds into a single joint within a consecutive three-month period.
Measured: Baseline up to Week 52
Vector shedding of VGB-R04
Saliva, urine and semen will be collected to assess clearance of vector genomes.
Measured: Baseline up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2021
- Study start28 Dec 2021
- Primary completionMar 2025 (estimated)
- Study completionDec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- More trials run by Institute of Hematology & Blood Diseases Hospital, ChinaThe 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
- 3 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lei Zhang, Doctor, Principal investigator, Institute of Hematology & Blood Diseases Hospital, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05152732
- Sponsor's protocol ID
- IIT2021043
- Status last verified
- May 2024
- First submitted
- 29 Nov 2021
- Last updated
- 21 Feb 2025
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD will be shared with other researchers when VGB-R04 is fully approved.
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Tolerability of VGB-R04 in Patients With Haemophilia B
- ClinicalTrials.gov ID
- NCT05152732
- Acronym / sponsor ID
- IIT2021043
- Conditions
- Hemophilia B
- Keywords
- Hemophilia, AAV, safety, gene therapy
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 28 Dec 2021 (actual)
- Primary completion
- Mar 2025 (estimated)
- Study completion
- Dec 2025 (estimated)
- First posted
- 10 Dec 2021 (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.
An Open-Label, Non-Randomized, uncontrolled, single-dose pilot study of VGB-R04 in subjects with Hemophilia B.
Detailed description
Hemophilia B is a genetic bleeding disorder caused by pathogenic variants (eg, mutations, deletion) in the FIX gene. HB patients have frequent and potentially life-threatening bleeding and often develop progressive physical disability and pain from chronic haemarthropathy. Current replacement therapy needs regular treatment in the life-long time, bringing heavy economic and social burdens.
VGB-R04 is a novel AAV vector carrying a high specific activity factor IX variant. This study is intended to evaluate the safety, tolerability and kinetics of a single IV infusion of VGB-R04. All subjects in this study will provide informed consent and then undergo screening assessments up to 6 weeks before administration of VGB-R04. All subjects will undergo 52(±2) weeks of safety observation and will be encouraged to enroll in an extension study to evaluate the long-term safety of VGB-R04 for a total of five years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| VGB-R04 | Experimental | Genetic: VGB-R04Single intravenous (i.v.) infusion of VGB-R04 Intervention: Gene Therapy / Gene Transfer |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male ≥18 years and ≤75years of age;
- Confirmed diagnosis of hemophilia B (baseline FIX activity ≤ 2% of normal or documented history of FIX activity ≤2%);
- At least 100 days exposure history to FIX;
- Currently receiving FIX Prophylaxis therapy or on-demand treatment to prevent bleeding;
- Have acceptable laboratory values:
Key exclusion criteria (17 listed)
- Have significant underlying liver disease within the past 6 months prior to or at Screening, including but not limited to:
- Have anti-VGB-R04 neutralizing antibody titers ≥1:5;
- Evidence of severe infection disease, i.e., human immunodeficiency virus (HIV) infection, syphilis, tuberculosis, etc.;
- Evidence of active hepatitis B virus infection (HBV-DNA >103 IU/ml) or hepatitis C virus infection (HCV antigen and HCV-RNA positive);
- Evidence of malignant tumours or those with a previous history of malignant tumours;
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 |
|---|---|---|
| VGB-R04A novel, bioengineered adeno-associated viral (AAV) vector carrying human factor IX variant | Genetic | VGB-R04 |
Primary outcome
Incidence of adverse events
Time frame: Baseline up to Week 52
An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant administered a product; the event will not need to have a causal relationship with the treatment.
Incidence of serious adverse events
Time frame: Baseline up to Week 52
A serious adverse event (SAE) is any untoward medical occurrence at any dose that resulted in death; life threatening; require inpatient hospitalization or prolongation of existing hospitalization; result in persistent or significant disability/incapacity; result in congenital anomaly/birth defect
Number of Participants with Clinically Significant Change from Baseline in Vital Signs
Time frame: Baseline up to Week 52
Vital signs (temperature, respiratory rate, pulse rate, systolic and diastolic blood pressure) will be obtained with participants in the seated position, after having sat calmly for at least 5 minutes. The clinical significance of vital signs will be determined at the investigator's discretion
Number of Participants with Clinically Significant Change From Baseline in Physical Examination Findings
Time frame: Baseline up to Week 52
The physical examination will include examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination will assess the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings will be considered to be clinically significant based on the investigator's decision
Number of Participants with Clinical Laboratory Abnormalities
Time frame: Baseline up to Week 52
Physical examination included examination of the head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, musculoskeletal, and neurological systems. The examination assessed the participants for any potential changes in general appearance, the respiratory and cardiovascular systems, as well as towards participant-reported symptoms. Findings were considered to be clinically significant based on the investigator's decision.
6 secondary outcomes
Vector- derived FIX:C Activity
Time frame: Baseline up to Week 52
Vector- derived FIX antigen levels
Time frame: Baseline up to Week 52
Annualized bleeding rate changes from baseline
Time frame: Baseline up to Week 52
Annualized FIX consumption changes from baseline
Time frame: Baseline up to Week 52
Number of target joints
Time frame: Baseline up to Week 52
Vector shedding of VGB-R04
Time frame: Baseline up to Week 52
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2025.
- Individual participant dataSharing planned: Yes. IPD will be shared with other researchers when VGB-R04 is fully approved.
Related trials for Hemophilia B
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
Not yet recruitingPhase 1
Lentiviral FIX Gene Therapy
Hemophilia B
RecruitingPhase 3
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or B
Hemophilia
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. This study is not recruiting at the moment.
Lei Zhang, Doctor principal investigator
Institute of Hematology & Blood Diseases Hospital, China
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 VGB-R04 in people with Hemophilia B, run by Institute of Hematology & Blood Diseases Hospital, China 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 13 inclusion and 17 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: status not confirmed, as of the sponsor's last update on 21 Feb 2025. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Lei Zhang, Doctor (+86-13502118379, zhanglei1@ihcams.as.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of adverse events (time frame: Baseline up to Week 52). The study lists 5 primary outcomes in all. 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 21 Feb 2025.