Hemophilia BPhase 1NCT05709288
Gene Therapy for Hemophilia B Patients Aged 12-18 Years Old
A Phase 1 study testing BBM-H901 in people with Hemophilia B, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.
Trial summary
This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. Read more about this study
- Who is it for?
- Ages 12 to 18 years, men only
- Conditions the study is for
- Hemophilia B
- What is being tested?
- BBM-H901
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteChina
- Study dates
- 23 Mar 2023to Nov 2035
- Phase
- 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 12 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subjects and statutory guardian must be able to understand the purpose and risks of the study and provide signed and dated informed consent;
- Be male and 12≤ age <18 years of age, body wight ≥ 50kg;
- 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) ;
- Had had ≥75 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
- With ≤ 1:4 neutralizing antibodies and ≤1:200 binding antibodies against BBM-H901 capsid;
- Subjects with bleeding episode and/ or FIX agents infusion events within 12 weeks prior to screening;
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- Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
- Have no measurable FIX inhibitor as assessed by laboratory; or documented no prior history of FIX inhibitor (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 ≤1.5x upper limit of normal at the testing laboratory;
- Bilirubin ≤1.5x ULN ;
- glomerular filtration rate eGFR ≥ 60ml/min.
- For those subjects with sexual maturity, subject and statutory guardian must know that subjects must agree to use reliable barrier contraception until 52 weeks;
- with good compliance to the schedule of visit and fill in the subject diary.
Who cannot join
- Hepatitis B surface antigen antibody (HBSAg-Ab) or HBV-DNA positive; hepatitis C antibody or HCV-RNA positive;
- Currently on antiviral therapy for hepatitis B or C;
- With coagulation disorders other than hemophilia B;
- Had immunosuppressive therapy other than steroid and other suggested IST agents within 30 days prior to screening;
- Had vaccine 30 days prior to screening or have scheduled vaccination plan during the study (up to 52 weeks);
- Have significant underlying liver disease, as defined by a preexisting diagnosis of portal hypertension, splenomegaly, encephalopathy, etc; other liver conditions unsuitable to gene therapy judged by investigator;
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- Have surgery plan within 52 weeks after gene therapy;
- Have history of chronic infection or high rish of infection that the Investigator considers to constitute an unacceptable risk;
- Had 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;
- Had any herb that may affect the liver function within 4 weeks prior to screening;
- Have history of fatal bleeding episode, eg intracranial hemorrhage, etc;
- 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. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Institute of haematology and Blood diseases hospital
Tianjin, Tianjin Municipality, 300020
Lei Zhang, MD, 0862223909009, zhanglei1@ihcams.ac.cn
Feng Xue, MD, +862223909240, xuefeng@ihcams.ac.cn
About this study
Official title: A Pilot Study Evaluating the Safety, Tolerability and Efficacy of Gene Therapy With BBM-H901 in Hemophilia B Patients Aged 12-18 Years Old
This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. 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
This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. 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. Nine subjects will be enrolled and administered with single infusion of BBM-H901, an AAV at one dose level of 5x10'12 vg/Kg. Subjects and statutory guardian must 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 continuously followed up to evaluate long- term safety and efficacy of BBM-H901 up to ten years. The first subject will be dosed at 5x10'12 vg/Kg and undergo 8 weeks safety observation of which the data will undergo review by an independent safety committee.
- Conditions
- Hemophilia B
- Being tested
- BBM-H901
- Keywords
- gene therapy, AAV
- Medical subject headings
- Hemophilia B
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BBM-H901Drug
Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of an hyper active human factor IX mutant(FIX Padua) transgene in liver. The dose of BBM-H901 is 5x10'12 vg/Kg.
| Study group | Role | What they receive |
|---|---|---|
| BBM-H901 administration group | Experimental | Subjects will be administered with single dose intravenous infusion of BBM-H901. Receives: Drug: BBM-H901 |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of treatment related adverse events deemed related to BBM-H901 within 10 weeks after vector administration
the type and incidence of TRAE after BBM-H901 infusion according to the CTCAE(v5.0)
Measured: infusion to 10 weeks after vector infusion.
The incidence of adverse events and serious adverse events within 52 weeks after BBM-H901 administration
Number of patients experiencing treatment-related adverse events from vector infusion to 52 weeks after vector infusion.
Measured: Vector infusion to 52 weeks after gene therapy.
Change from baseline aspartate amino transferase
number of subjects with elevation of AST. Number of episodes of elevating AST
Measured: At multiple timepoints from pre-dose through up to 1 years post-dose
Change from baseline alanine aminotransferase
number of subjects with elevation of ALT. Number of episodes of elevating ALT
Measured: At multiple timepoints from pre-dose through up to 1 years post-dose
Secondary outcomes (6)
Vector shedding after BBM-H901 infusion
Vector genome in plasma, urea, stool, saliva will be monitored
Measured: multiple timepoints until 2 consecutive negative results achieved usually within 52 weeks
Vector derived Factor IX(FIX) activity
FIX:C measured using one- stage APTT based method
Measured: infusion to 52 weeks after gene therapy
Annualized bleeding rate(ABR) after gene therapy
ABR will be prospectively collected at each visit.
Measured: vector infusion to 52 weeks after gene therapy
Times of infusion of factor IX agents
Times of infusion of factor IX agents, eg FIX concentrates, prothrombin complex concentrate, fresh- frozen plasma.
Measured: vector infusion to 52 weeks after gene therapy
number of target joint
target joint is defined as a joint with ≥bleeding during the last 6 months
Measured: vector infusion to 52 weeks after gene therapy
factor IX inhibitor
factor IX inhibitor will be measured using bethesda method
Measured: vector infusion to 52 weeks after gene therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start23 Mar 2023
- Primary completionJun 2035 (estimated)
- Study completionNov 2035 (estimated)
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Hemophilia B patients
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lei Zhang, MD, Principal investigator, Insitute of haematology and blood diseases hospital, chinese academy of medical sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05709288
- Sponsor's protocol ID
- IIT2022051
- Status last verified
- Jan 2025
- First submitted
- 19 Jan 2023
- 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, Zhang A, Ju M, Wu X, Xu B, Pei X, Wang Y, Liu W, Liu A, Jiang W, Dai X, Chen Y, Liu X, Fu R, Sun T, Gu W, Zheng J, Du Z, Yang C, Xiao X, Yang R, Hu Q, Zhang L. Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial. Nat Med. 2026 Sep 16. doi: 10.1038/s41591-026-04636-8. Online ahead of print.
PubMed 42749889
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
- A Pilot Study Evaluating the Safety, Tolerability and Efficacy of Gene Therapy With BBM-H901 in Hemophilia B Patients Aged 12-18 Years Old
- ClinicalTrials.gov ID
- NCT05709288
- Acronym / sponsor ID
- IIT2022051
- Conditions
- Hemophilia B
- Keywords
- gene therapy, AAV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Institute of Hematology & Blood Diseases Hospital, ChinaUniversity, hospital or other
- Study start
- 23 Mar 2023 (actual)
- Primary completion
- Jun 2035 (estimated)
- Study completion
- Nov 2035 (estimated)
- First posted
- 2 Feb 2023 (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 is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. 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
This is a Phase 1, open- label, non- randomized, uncontrolled, single dose pilot study to evaluate the safety, tolerability and efficacy of a single intravenous infusion of BBM-H901 in hemophilia B subjects with ≤2IU/dl residual FIX levels and aged 12-18 years old. 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. Nine subjects will be enrolled and administered with single infusion of BBM-H901, an AAV at one dose level of 5x10'12 vg/Kg. Subjects and statutory guardian must 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 continuously followed up to evaluate long- term safety and efficacy of BBM-H901 up to ten years. The first subject will be dosed at 5x10'12 vg/Kg and undergo 8 weeks safety observation of which the data will undergo review by an 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 |
|---|---|---|
| BBM-H901 administration group | Experimental | Drug: BBM-H901Subjects will be administered with single dose intravenous infusion of BBM-H901. |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Subjects and statutory guardian must be able to understand the purpose and risks of the study and provide signed and dated informed consent;
- Be male and 12≤ age <18 years of age, body wight ≥ 50kg;
- 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) ;
- Had had ≥75 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subject's record/history;
- With ≤ 1:4 neutralizing antibodies and ≤1:200 binding antibodies against BBM-H901 capsid;
Key exclusion criteria (12 listed)
- Hepatitis B surface antigen antibody (HBSAg-Ab) or HBV-DNA positive; hepatitis C antibody or HCV-RNA positive;
- Currently on antiviral therapy for hepatitis B or C;
- With coagulation disorders other than hemophilia B;
- Had immunosuppressive therapy other than steroid and other suggested IST agents within 30 days prior to screening;
- Had vaccine 30 days prior to screening or have scheduled vaccination plan during the study (up to 52 weeks);
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 |
|---|---|---|
| BBM-H901Single dose intravenous infusion of BBM-H901, an adeno-associated viral (AAV) vector designed to drive expression of an hyper active human factor IX mutant(FIX Padua) transgene in liver. The dose of BBM-H901 is 5x10'12 vg/Kg. | Drug | BBM-H901 administration group |
Primary outcome
The incidence of treatment related adverse events deemed related to BBM-H901 within 10 weeks after vector administration
Time frame: infusion to 10 weeks after vector infusion.
the type and incidence of TRAE after BBM-H901 infusion according to the CTCAE(v5.0)
The incidence of adverse events and serious adverse events within 52 weeks after BBM-H901 administration
Time frame: Vector infusion to 52 weeks after gene therapy.
Number of patients experiencing treatment-related adverse events from vector infusion to 52 weeks after vector infusion.
Change from baseline aspartate amino transferase
Time frame: At multiple timepoints from pre-dose through up to 1 years post-dose
number of subjects with elevation of AST. Number of episodes of elevating AST
Change from baseline alanine aminotransferase
Time frame: At multiple timepoints from pre-dose through up to 1 years post-dose
number of subjects with elevation of ALT. Number of episodes of elevating ALT
6 secondary outcomes
Vector shedding after BBM-H901 infusion
Time frame: multiple timepoints until 2 consecutive negative results achieved usually within 52 weeks
Vector derived Factor IX(FIX) activity
Time frame: infusion to 52 weeks after gene therapy
Annualized bleeding rate(ABR) after gene therapy
Time frame: vector infusion to 52 weeks after gene therapy
Times of infusion of factor IX agents
Time frame: vector infusion to 52 weeks after gene therapy
number of target joint
Time frame: vector infusion to 52 weeks after gene therapy
factor IX inhibitor
Time frame: vector infusion to 52 weeks after gene therapy
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 21 Feb 2025.
- Derived from this study: PubMed 42749889Xue F, Zhang A, Ju M, Wu X, Xu B, Pei X, Wang Y, Liu W, Liu A, Jiang W, Dai X, Chen Y, Liu X, Fu R, Sun T, Gu W, Zheng J, Du Z, Yang C, Xiao X, Yang R, Hu Q, Zhang L. Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial. Nat Med. 2026 Sep 16. doi: 10.1038/s41591-026-04636-8. Online ahead of print.
- 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.
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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.
Lei Zhang, MD principal investigator
Insitute of haematology and blood diseases hospital, chinese academy of medical sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing 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 16 inclusion and 12 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 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 Feng Xue, MD (+862223909240, xuefeng@ihcams.ac.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of treatment related adverse events deemed related to BBM-H901 within 10 weeks after vector administration (time frame: infusion to 10 weeks after vector infusion.). The study lists 4 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 NCT05709288, 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.