- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05709288
Gene Therapy for Hemophilia B Patients Aged 12-18 Years Old
February 6, 2023 updated by: Zhang Lei, MD, Institute of Hematology & Blood Diseases Hospital
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.
Study Overview
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 Type
Interventional
Enrollment (Anticipated)
9
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Feng Xue, MD
- Phone Number: +862223909240
- Email: xuefeng@ihcams.ac.cn
Study Contact Backup
- Name: Shuo Chen, BS
- Phone Number: +862223909009
- Email: Chenshuo@ihcams.ac.cn
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
12 years to 18 years (ADULT, CHILD)
Accepts Healthy Volunteers
No
Genders Eligible for Study
Male
Description
Inclusion Criteria:
- 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;
- 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.
Exclusion Criteria:
- 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;
- 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;
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: BBM-H901 administration group
Subjects will be administered with single dose intravenous infusion of BBM-H901.
|
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.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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)
|
infusion to 10 weeks after vector infusion.
|
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.
|
Vector infusion to 52 weeks after gene therapy.
|
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
|
At multiple timepoints from pre-dose through up to 1 years post-dose
|
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
|
At multiple timepoints from pre-dose through up to 1 years post-dose
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vector shedding after BBM-H901 infusion
Time Frame: multiple timepoints until 2 consecutive negative results achieved usually within 52 weeks
|
Vector genome in plasma, urea, stool, saliva will be monitored
|
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
|
FIX:C measured using one- stage APTT based method
|
infusion to 52 weeks after gene therapy
|
Annualized bleeding rate(ABR) after gene therapy
Time Frame: vector infusion to 52 weeks after gene therapy
|
ABR will be prospectively collected at each visit.
|
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
|
Times of infusion of factor IX agents, eg FIX concentrates, prothrombin complex concentrate, fresh- frozen plasma.
|
vector infusion to 52 weeks after gene therapy
|
number of target joint
Time Frame: vector infusion to 52 weeks after gene therapy
|
target joint is defined as a joint with ≥bleeding during the last 6 months
|
vector infusion to 52 weeks after gene therapy
|
factor IX inhibitor
Time Frame: vector infusion to 52 weeks after gene therapy
|
factor IX inhibitor will be measured using bethesda method
|
vector infusion to 52 weeks after gene therapy
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Long term factor IX activity
Time Frame: 52 weeks after gene therapy to up to 10 years
|
factor IX activity will be measured using one stage APTT based method
|
52 weeks after gene therapy to up to 10 years
|
Long term Annualized bleeding rate
Time Frame: 52 weeks after gene therapy to up to 10 years
|
Annualized bleeding rate will be calculated based on the bleeding times and time interval
|
52 weeks after gene therapy to up to 10 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Lei Zhang, MD, Insitute of haematology and blood diseases hospital, chinese academy of medical sciences
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (ANTICIPATED)
March 1, 2023
Primary Completion (ANTICIPATED)
June 1, 2035
Study Completion (ANTICIPATED)
November 1, 2035
Study Registration Dates
First Submitted
January 19, 2023
First Submitted That Met QC Criteria
January 31, 2023
First Posted (ACTUAL)
February 2, 2023
Study Record Updates
Last Update Posted (ESTIMATE)
February 9, 2023
Last Update Submitted That Met QC Criteria
February 6, 2023
Last Verified
February 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- BBM001-IIT1002
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
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.
IPD Sharing Time Frame
From 12 months 36 months after study completion.
IPD Sharing Access Criteria
Upon request to PI.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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