Hemophilia BNCT04135300

Gene Therapy for Chinese Hemophilia B

A study testing Single dose intravenous injection of BBM-H901 in people with Hemophilia B, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 years and older, men only
Conditions the study is for: Hemophilia B
What is being tested?: Single dose intravenous injection of BBM-H901
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 10 participants
Where: 1 siteChina
Study dates: 16 Oct 2019to 7 Jan 2022
Phase: Interventional
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 years and older
Men only
No healthy volunteers
Adult, Older adult

Who may be able to join

Be able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations;
Be male and ≥18 years of age;
Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels as documented by a certified clinical laboratory at the time of screening. If the screening result is >2% due to insufficient washout from FIX protein product, then the severity of hemophilia B may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤2% FIX coagulant activity (FIX:C) ;
Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
a. Prophylaxis subjects: have had bleeding events and/or infusions with FIX protein products during the last 12 weeks documented in the subjects' medical records; OR b. On-demand subjects: have had ≥4 bleeding events in the last 52 weeks and/or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints;
Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;

Show all 14Show fewer

Have no measurable FIX inhibitor as assessed by laboratory; or documented no prior history of FIX inhibitor after 50 EDs (family history of inhibitors will not exclude the subject) and no clinical signs or symptoms of decreased response to FIX administration;
Have acceptable laboratory values:
Hemoglobin ≥11 g/dL;
Platelets ≥100,000 cells/μL;
AST, ALT, alkaline phosphatase ≤2x upper limit of normal at the testing laboratory;
Bilirubin ≤3x ULN ;
Creatinine ≤2.0 mg/dL.
Agree to use reliable barrier contraception until 52 weeks and semen samples after the administration of BBM- H901 are negative for vector sequences.

Who cannot join

Have active hepatitis B or C, and HBsAg, hepatitis B core antibody, hepatitis B virus-DNA positivity or hepatitis C virus-RNA viral load positivity, respectively. Negative viral assays in two samples, collected at least six months apart, will be required to be considered negative. Both natural clearers and those who have cleared hepatitis C virus on antiviral therapy are eligible;
Currently on antiviral therapy for hepatitis B or C;
Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, reduction below normal limits of serum albumin or evidence of significant liver fibrosis (fibrosis stage ≥ 3) within the past 6 months prior to or at Screening as determined by any of the following diagnostic modalities: AST-to-Platelet Ratio Index (APRI) >1;
Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Subjects who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load (<50 gc/mL) measured twice in the six months prior to enrollment, on an antiretroviral drug regimen are eligible to enroll;
Have anti-BBM-H901 neutralizing antibody titers ≥1:5;
Have history of chronic infection or other chronic disease that the Investigator considers to constitute an unacceptable risk;

Show all 9Show fewer

Have participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the last 12 weeks;
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;
Unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol.

Trial locations and contacts

1 site in 1 country.

China1 site

Institute of Hematology & Blood Diseases Hospital
Tianjin, Tianjin Municipality, 300020

Other trials in China

About this study

Official title: Gene Therapy for Chinese Hemophilia B With Adeno-associated Virus (AAV) Vector

GT2019001 is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels. BBM-H901 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating levels of endogenous FIX.

Read the detailed description

GT2019001 is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels. Three subjects will be enrolled and administered with single infusion of BBM-H901, an AAV at one dose level of 5x1012 vg/Kg.Subjects will provide informed consent and then undergo screening assessments up to 4-8weeks prior administration of BBM-H901. All subjects will undergo 52(+- 2) weeks safety observation and will be encouraged to enroll in an extension study to evaluate long- term safety of BBM-H901 for a total 5 years.The first subject will be dosed at 5x1012 vg/Kg and undergo 2 months safety observation of which the data will undergo review by an independent safety committee. The dosing to the second subject will not be performed until acquiring the approve from independent safety committee.

Conditions: Hemophilia B
Being tested: Single dose intravenous injection of BBM-H901
Keywords: Hemophilia B, gene therapy, ADENO-ASSOCIATED VIRUSES
Medical subject headings: Hemophilia B

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Single dose intravenous injection of BBM-H901Genetic
Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene in liver. The dose of BBM-H901 will be 5x10'12 vg/Kg.

Study groups in NCT04135300
Study group	Role	What they receive
Arm of BBM-H901	Experimental	Subjects will be dosed with single dose of BBM-H901 at 5x10·12 vg/kg via intravenous infusion. Receives: Genetic: Single dose intravenous injection of BBM-H901

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of treatment- related adverse events
Number of patients experiencing treatment-related adverse events. Including inhibitor development.
Measured: Infusion to the end of study, average 1 year.
Change from baseline alanine aminotransferase ans aspartate amino transferase
liver function tests include ALT, AST.
Measured: At multiple timepoints from pre-dose through up to 1 years post-dose
Antibody against AAV capsid protein
Immune response against AAV capsid will be evaluated by measurement of the total antibody and neutralizing antibody against AAV capsid protein in plasma samples collected at multiple timepoints after dosing up to 1 year.
Measured: from screening through up to 1 years

Secondary outcomes (1)

Vector- derived FIX:C and FIX antigen levels.
Vector- derived FIX:C and FIX antigen levels will be measured after dosing.
Measured: At multiple timepoints from pre-dose through up to 1 years post-dose

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

16 Oct 20197 Jan 2022

First posted22 Oct 2019
Study start16 Oct 2019
Primary completion7 Jan 2022
Study completion7 Jan 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
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: Phase N/A
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Model description: Hemophilia B patients
Masking: None (open label)
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04135300
Sponsor's protocol ID: GT2019001
Status last verified: Nov 2023
First submitted: 8 Oct 2019
Last updated: 21 Feb 2025
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.

Publications

Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, Du Z, Jiang W, Zhong C, Wei J, Zhu P, Fu R, Liu X, Chen L, Pei X, Sun J, Cheng T, Yang R, Xiao X, Zhang L. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 2022 Jul;9(7):e504-e513. doi: 10.1016/S2352-3026(22)00113-2. Epub 2022 May 19.
PubMed 35598604

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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

All Hemophilia B trials

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: Gene Therapy for Chinese Hemophilia B With Adeno-associated Virus (AAV) Vector
ClinicalTrials.gov ID: NCT04135300
Acronym / sponsor ID: GT2019001
Conditions: Hemophilia B
Keywords: Hemophilia B, gene therapy, ADENO-ASSOCIATED VIRUSES
Study type: Interventional
Recruitment status: Completed
Enrolment: 10 participants (actual)
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
Collaborators: East China University of Science and Technology
Study start: 16 Oct 2019 (actual)
Primary completion: 7 Jan 2022 (actual)
Study completion: 7 Jan 2022 (actual)
First posted: 22 Oct 2019 (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.

GT2019001 is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels. BBM-H901 is an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene and raise circulating levels of endogenous FIX.

Detailed description

GT2019001 is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels. Three subjects will be enrolled and administered with single infusion of BBM-H901, an AAV at one dose level of 5x1012 vg/Kg.Subjects will provide informed consent and then undergo screening assessments up to 4-8weeks prior administration of BBM-H901. All subjects will undergo 52(+- 2) weeks safety observation and will be encouraged to enroll in an extension study to evaluate long- term safety of BBM-H901 for a total 5 years.The first subject will be dosed at 5x1012 vg/Kg and undergo 2 months safety observation of which the data will undergo review by an independent safety committee. The dosing to the second subject will not be performed until acquiring the approve from independent safety committee.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: Hemophilia B patients

Arm	Type	Receives
Arm of BBM-H901	Experimental	Genetic: Single dose intravenous injection of BBM-H901Subjects will be dosed with single dose of BBM-H901 at 5x10·12 vg/kg via intravenous infusion.

Who may qualify

Ages: 18 years and older
Sex: Male only
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Be able to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations;
Be male and ≥18 years of age;
Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels as documented by a certified clinical laboratory at the time of screening. If the screening result is >2% due to insufficient washout from FIX protein product, then the severity of hemophilia B may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤2% FIX coagulant activity (FIX:C) ;
Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
a. Prophylaxis subjects: have had bleeding events and/or infusions with FIX protein products during the last 12 weeks documented in the subjects' medical records; OR b. On-demand subjects: have had ≥4 bleeding events in the last 52 weeks and/or chronic hemophilic arthropathy (pain, joint destruction, and loss of range of motion) in one or more joints;

Key exclusion criteria (9 listed)

Have active hepatitis B or C, and HBsAg, hepatitis B core antibody, hepatitis B virus-DNA positivity or hepatitis C virus-RNA viral load positivity, respectively. Negative viral assays in two samples, collected at least six months apart, will be required to be considered negative. Both natural clearers and those who have cleared hepatitis C virus on antiviral therapy are eligible;
Currently on antiviral therapy for hepatitis B or C;
Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, reduction below normal limits of serum albumin or evidence of significant liver fibrosis (fibrosis stage ≥ 3) within the past 6 months prior to or at Screening as determined by any of the following diagnostic modalities: AST-to-Platelet Ratio Index (APRI) >1;
Have serological evidence of HIV-1 or HIV-2 with CD4 counts ≤200/mm3. Subjects who are HIV-positive and stable, with an adequate CD4 count (>200/mm3) and undetectable viral load (<50 gc/mL) measured twice in the six months prior to enrollment, on an antiretroviral drug regimen are eligible to enroll;
Have anti-BBM-H901 neutralizing antibody titers ≥1:5;

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
Single dose intravenous injection of BBM-H901Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of the human factor IX (hFIX) transgene in liver. The dose of BBM-H901 will be 5x10'12 vg/Kg.	Genetic	Arm of BBM-H901

Primary outcome

Incidence of treatment- related adverse events
Time frame: Infusion to the end of study, average 1 year.
Number of patients experiencing treatment-related adverse events. Including inhibitor development.
Change from baseline alanine aminotransferase ans aspartate amino transferase
Time frame: At multiple timepoints from pre-dose through up to 1 years post-dose
liver function tests include ALT, AST.
Antibody against AAV capsid protein
Time frame: from screening through up to 1 years
Immune response against AAV capsid will be evaluated by measurement of the total antibody and neutralizing antibody against AAV capsid protein in plasma samples collected at multiple timepoints after dosing up to 1 year.

1 secondary outcome

Vector- derived FIX:C and FIX antigen levels.
Time frame: At multiple timepoints from pre-dose through up to 1 years post-dose

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2025.
Derived from this study: PubMed 35598604Xue F, Li H, Wu X, Liu W, Zhang F, Tang D, Chen Y, Wang W, Chi Y, Zheng J, Du Z, Jiang W, Zhong C, Wei J, Zhu P, Fu R, Liu X, Chen L, Pei X, Sun J, Cheng T, Yang R, Xiao X, Zhang L. Safety and activity of an engineered, liver-tropic adeno-associated virus vector expressing a hyperactive Padua factor IX administered with prophylactic glucocorticoids in patients with haemophilia B: a single-centre, single-arm, phase 1, pilot trial. Lancet Haematol. 2022 Jul;9(7):e504-e513. doi: 10.1016/S2352-3026(22)00113-2. Epub 2022 May 19.
Individual participant dataSharing planned: Yes. Researchers qualified can request the dataset, including de-identified individual subject data. Data may be requested from PI from 12 months 36 months after study completion.

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, MD 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 study testing Single dose intravenous injection of BBM-H901 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 14 inclusion and 9 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: finished, 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.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of treatment- related adverse events (time frame: Infusion to the end of study, average 1 year.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04135300, which also lists 1 linked publication.

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.