Hemophilia BPhase 2/3NCT05203679
Evaluation of the Safety and Efficacy of Hemophilia B Gene Therapy Drug
A Phase 2/3 study testing Single dose intravenous injection of BBM-H901 in people with Hemophilia B, run by Shanghai Xinzhi BioMed Co., Ltd. at 9 sites in China.
Trial summary
This is a multi-center, Phase 1/2/3, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of BBM-H901 injection in Hemophilia B subjects with ≤2 International unit per deciliter (IU/dl) residual factor IX (FIX) levels. Read more about this study
- 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
- 32 participants
- Where
- 9 sitesChina
- Study dates
- 30 Dec 2021to 30 Jun 2028
- Phase
- Phase 2/3
- 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 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males ≥ 18 years of age;
- Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
- Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subjects' records/histories;
- Have had bleeding events and/or injected with FIX protein products (including recombination and plasma source) during the last 12 weeks documented in the subjects' medical records;
- Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
- Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after administration.
Who cannot join
- Being positive for hepatitis B surface antigen (HBsAg) or hepatitis B virus-DNA (HBV-DNA). Being positive for hepatitis C virus antibody (HCV-Ab) or hepatitis C virus RNA (HCV-RNA). Subjects with medical history of hepatitis B or C can be regarded as negative only when 2 required samplings are conducted at least 3 months apart and both test results of indicators aforementioned are negative, i.e. subjects with natural clearance and anti-viral therapy clearance for hepatitis B or C are eligible;
- Have potential liver diseases, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy or liver fibrosis (fibrosis stage ≥ 3); nodules or cysts were found by B ultrasound, or elevated alpha-fetoprotein was detected by laboratory tests. Subjects who are not eligible for the study if the abnormalities are clinically significant regarding to the medical judgement of the investigator;
- HIV positive patients;
- Have participated in a previous gene therapy research trial before screening, or in a clinical study with an investigational drug within 5 half-life of the investigational product, whichever is longer;
- Have alcohol or drug dependence, or cannot stop drinking throughout the study;
- Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
China9 sites
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100005
Nanfang Hospital Southern Medical University
Guangzhou, Guangdong, 510515
Anhui Provincial Hospital
Hefei, Anhui, 230022
The second Affiliated Hospital of Kunming Medical University
Kunming, Yunnan, 650032
The Second People's Hospital of Shenzhen
Shenzhen, Guangdong, 518025
The Second Hospital of Shanxi Medical University
Taiyuan, Shanxi, 030001
North China University of Science and Technology Affiliated Hospital
Tangshan, Hebei, 063000
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
Tianjin, Tianjin Municipality, 300020
Henan Cancer Hospital
Zhengzhou, Henan, 450003
About this study
Official title: A Phase 1/2/3 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Virus Vector Containing an Expression Cassette of the Human Factor IX Transgene (BBM-H901) Injection in Patients With Hemophilia B
This is a multi-center, Phase 1/2/3, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of BBM-H901 injection in Hemophilia B subjects with ≤2 International unit per deciliter (IU/dl) residual factor IX (FIX) levels.
BBM-H901 is an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene and raises circulating levels of endogenous FIX.
- Conditions
- Hemophilia B
- Being tested
- Single dose intravenous injection of BBM-H901
- Keywords
- Hemophilia B;gene therapy;Adeno-Associated Virus
- 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 virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene in liver.
| Study group | Role | What they receive |
|---|---|---|
| Arm of BBM-H901 | Experimental | Single-dose treatment 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.
Phase 1/2: The incidence of dose limiting toxicity (DLT) events
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-H901 injection infusion.
Measured: 10 weeks post-infusion
Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs)
To assess the safety of BBM-H901 Injection by AEs and SAEs.
Measured: 10 weeks post-infusion
Phase 1/2: Changes in liver function
To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Measured: 10 weeks post-infusion
Phase 3: Annualized bleeding rate (ABR)
To assess ABR, including spontaneous bleeding and traumatic bleeding after administration.
Measured: 52 weeks post-infusion
Secondary outcomes (9)
Phase 1/2: Changes in liver function
To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Measured: 52 weeks post-infusion
Phase 1/2/3: Mean FIX Padua Activity Level
Measurement of mean FIX Padua activity levels over the 52-week period following BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: Other FIX Protein Product Usage
Number and total volume of infusions of exogenous FIX protein products (recombinant or plasma-derived) administered within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: Target Joint Count
Number of target joints recorded within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: Joint Bleeding Episodes
Total number of joint bleeding events occurring within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: Bleeding-Free Subjects
Proportion of subjects experiencing no bleeding events within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: Adverse Event Incidence
Incidence of adverse events (AEs) and serious adverse events (SAEs) within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: FIX Inhibitor Incidence
Incidence of FIX inhibitors measured by Bethesda or Nijmegen-Bethesda assays within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Phase 1/2/3: AAV Vector Shedding
Changes in AAV vector shedding in plasma, urine, semen, saliva, and PBMCs within 52 weeks post-BBM-H901 injection.
Measured: 52 weeks post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2022
- Study start30 Dec 2021
- Primary completion16 Apr 2024
- Study completion30 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Hemophilia BStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Shanghai Xinzhi BioMed Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Lei Zhang, MD, Study chair, Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical CollegeCaifeng Yang, Master, Study director, Shanghai Xinzhi BioMed Co., Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05203679
- Sponsor's protocol ID
- BBM001-CLN1001
- Status last verified
- Mar 2026
- First submitted
- 29 Dec 2021
- Last updated
- 1 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 35598604Xue F, Wang P, Yuan Z, Shi C, Fang Y, Liu W, Wang Y, Xiao X, Yang R, George LA, Zhang L. Total Knee Arthroplasty after Gene Therapy for Hemophilia B. N Engl J Med. 2022 Oct 27;387(17):1622-1624. doi: 10.1056/NEJMc2211173. No abstract available.
PubMed 36306204Wei H, Xiao W, Dai J. China's first approved gene therapy for hemophilia B: A new era for global AAV-based treatments. Mol Ther. 2025 Jun 4;33(6):2312-2313. doi: 10.1016/j.ymthe.2025.05.014. Epub 2025 May 28. No abstract available.
PubMed 40441148Xue F, Hu Y, Yang R, Sun J, Yang L, Wang X, Yu Z, Zhu T, Zhou H, Zhou Z, Yan Z, Du X, Zheng C, Liu W, Zhou R, Dai J, Yin J, Wang H, Tang LV, Chen S, Cheng H, Zhu M, Wang S, Song Y, Zhang P, Zhang L. Chinese guidance for the clinical application of adeno-associated virus vector-based gene therapy for hemophilia B (2025). Blood Sci. 2025 Oct 29;7(4):e00257. doi: 10.1097/BS9.0000000000000257. eCollection 2025 Dec.
PubMed 41180128Xue F, Ju M, Zhu T, Zhou Z, Sun J, Yang L, Yan Z, Zhou H, Du X, Zheng C, Zheng J, Wu X, Du Z, Jiang W, Yang C, Xiao X, Liu W, Yang R, Zhang L. Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials. Nat Med. 2026 Jan;32(1):93-102. doi: 10.1038/s41591-025-04012-y. Epub 2025 Nov 20.
PubMed 41266685
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2/3 Open-label Study to Evaluate the Safety, Tolerability and Efficacy of an Adeno-associated Virus Vector Containing an Expression Cassette of the Human Factor IX Transgene (BBM-H901) Injection in Patients With Hemophilia B
- ClinicalTrials.gov ID
- NCT05203679
- Acronym / sponsor ID
- BBM001-CLN1001
- Conditions
- Hemophilia B
- Keywords
- Hemophilia B;gene therapy;Adeno-Associated Virus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Shanghai Xinzhi BioMed Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 30 Dec 2021 (actual)
- Primary completion
- 16 Apr 2024 (actual)
- Study completion
- 30 Jun 2028 (estimated)
- First posted
- 24 Jan 2022 (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 multi-center, Phase 1/2/3, single-arm, open-label, single-dose treatment clinical study to evaluate the safety, tolerability and efficacy of BBM-H901 injection in Hemophilia B subjects with ≤2 International unit per deciliter (IU/dl) residual factor IX (FIX) levels.
BBM-H901 is an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene and raises circulating levels of endogenous FIX.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm of BBM-H901 | Experimental | Genetic: Single dose intravenous injection of BBM-H901Single-dose treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Males ≥ 18 years of age;
- Have hemophilia B with ≤2 IU/dL (≤2 %) endogenous FIX activity levels;
- Have had ≥100 prior exposure days (EDs) to any recombinant and/or plasma-derived FIX protein products based on historical data from the subjects' records/histories;
- Have had bleeding events and/or injected with FIX protein products (including recombination and plasma source) during the last 12 weeks documented in the subjects' medical records;
- Have no prior history of hypersensitivity or anaphylaxis associated with any FIX or IV immunoglobulin administration;
Key exclusion criteria (6 listed)
- Being positive for hepatitis B surface antigen (HBsAg) or hepatitis B virus-DNA (HBV-DNA). Being positive for hepatitis C virus antibody (HCV-Ab) or hepatitis C virus RNA (HCV-RNA). Subjects with medical history of hepatitis B or C can be regarded as negative only when 2 required samplings are conducted at least 3 months apart and both test results of indicators aforementioned are negative, i.e. subjects with natural clearance and anti-viral therapy clearance for hepatitis B or C are eligible;
- Have potential liver diseases, such as previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy or liver fibrosis (fibrosis stage ≥ 3); nodules or cysts were found by B ultrasound, or elevated alpha-fetoprotein was detected by laboratory tests. Subjects who are not eligible for the study if the abnormalities are clinically significant regarding to the medical judgement of the investigator;
- HIV positive patients;
- Have participated in a previous gene therapy research trial before screening, or in a clinical study with an investigational drug within 5 half-life of the investigational product, whichever is longer;
- Have alcohol or drug dependence, or cannot stop drinking throughout the study;
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 virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor IX (hFIX) transgene in liver. | Genetic | Arm of BBM-H901 |
Primary outcome
Phase 1/2: The incidence of dose limiting toxicity (DLT) events
Time frame: 10 weeks post-infusion
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) in DLT observation period after BBM-H901 injection infusion.
Phase 1/2: The incidence of adverse events (AEs) and serious adverse events (SAEs)
Time frame: 10 weeks post-infusion
To assess the safety of BBM-H901 Injection by AEs and SAEs.
Phase 1/2: Changes in liver function
Time frame: 10 weeks post-infusion
To assess changes in liver function before and after treatment, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST).
Phase 3: Annualized bleeding rate (ABR)
Time frame: 52 weeks post-infusion
To assess ABR, including spontaneous bleeding and traumatic bleeding after administration.
9 secondary outcomes
Phase 1/2: Changes in liver function
Time frame: 52 weeks post-infusion
Phase 1/2/3: Mean FIX Padua Activity Level
Time frame: 52 weeks post-infusion
Phase 1/2/3: Other FIX Protein Product Usage
Time frame: 52 weeks post-infusion
Phase 1/2/3: Target Joint Count
Time frame: 52 weeks post-infusion
Phase 1/2/3: Joint Bleeding Episodes
Time frame: 52 weeks post-infusion
Phase 1/2/3: Bleeding-Free Subjects
Time frame: 52 weeks post-infusion
Phase 1/2/3: Adverse Event Incidence
Time frame: 52 weeks post-infusion
Phase 1/2/3: FIX Inhibitor Incidence
Time frame: 52 weeks post-infusion
Phase 1/2/3: AAV Vector Shedding
Time frame: 52 weeks post-infusion
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 1 Apr 2026.
- Background: 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.
- Background: PubMed 36306204Xue F, Wang P, Yuan Z, Shi C, Fang Y, Liu W, Wang Y, Xiao X, Yang R, George LA, Zhang L. Total Knee Arthroplasty after Gene Therapy for Hemophilia B. N Engl J Med. 2022 Oct 27;387(17):1622-1624. doi: 10.1056/NEJMc2211173. No abstract available.
- Results publication: PubMed 40441148Wei H, Xiao W, Dai J. China's first approved gene therapy for hemophilia B: A new era for global AAV-based treatments. Mol Ther. 2025 Jun 4;33(6):2312-2313. doi: 10.1016/j.ymthe.2025.05.014. Epub 2025 May 28. No abstract available.
- Results publication: PubMed 41180128Xue F, Hu Y, Yang R, Sun J, Yang L, Wang X, Yu Z, Zhu T, Zhou H, Zhou Z, Yan Z, Du X, Zheng C, Liu W, Zhou R, Dai J, Yin J, Wang H, Tang LV, Chen S, Cheng H, Zhu M, Wang S, Song Y, Zhang P, Zhang L. Chinese guidance for the clinical application of adeno-associated virus vector-based gene therapy for hemophilia B (2025). Blood Sci. 2025 Oct 29;7(4):e00257. doi: 10.1097/BS9.0000000000000257. eCollection 2025 Dec.
- Results publication: PubMed 41266685Xue F, Ju M, Zhu T, Zhou Z, Sun J, Yang L, Yan Z, Zhou H, Du X, Zheng C, Zheng J, Wu X, Du Z, Jiang W, Yang C, Xiao X, Liu W, Yang R, Zhang L. Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials. Nat Med. 2026 Jan;32(1):93-102. doi: 10.1038/s41591-025-04012-y. Epub 2025 Nov 20.
- Prevalence of neutralizing antibodies against AAV8,AAV9, and AAV843 in a Chinese populationLink provided by the sponsor.
- 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. This study is not recruiting at the moment.
Lei Zhang, MD study chair
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
Caifeng Yang, Master study director
Shanghai Xinzhi BioMed Co., Ltd.
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Single dose intravenous injection of BBM-H901 in people with Hemophilia B, run by Shanghai Xinzhi BioMed Co., Ltd. at 9 sites 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 6 inclusion and 6 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: under way, not looking for participants, as of the sponsor's last update on 1 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
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?
Phase 1/2: The incidence of dose limiting toxicity (DLT) events (time frame: 10 weeks post-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 NCT05203679, which also lists 5 linked publications.
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 1 Apr 2026.