Back to resultsA Study of FVIII Gene Therapy for Hemophilia A
Primary Purpose
Hemophilia A
Status
Not yet recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Single dose intravenous injection of BBM 002
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A focused on measuring Hemophilia A; gene therapy; Adeno-Associated Virus
Eligibility Criteria
Inclusion Criteria:
- Subjects are fully aware of the purpose, nature, methods and possible adverse reactions of the trial and voluntarily sign informed consent.
- Males ≥ 18 years of age.
- Have hemophilia A with ≤2 IU/dL (≤2 %) endogenous FVIII activity levels.
- Have had ≥150 prior exposure days (EDs) to any recombinant and/or plasma-derived FVIII protein products.
- Have had bleeding events and/or infusions with FVIII 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 FVIII or IV immunoglobulin administration.
- Have no FVIII inhibitor. (eg <0.6BU/ml Bethesda Units; or the patient's FVIII inhibitor titer was detected <0.6BU/ml in 2 consecutive times within 1-4 weeks using Bethesda method or Nijmegen method), or no prior medical history of FVIII inhibitor after 150 EDs of FVIII products; no clinical signs or symptoms of decreased response to FVIII products infusion.
- Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after BBM002 infusion.
- Compliance is good, patients and their families have the will of 'gene therapy' clinical trials.
Exclusion Criteria:
- 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).
- Currently on antiviral therapy for hepatitis B or C.
- Patients with coagulation disorders in addition to hemophilia A.
- Use of any other systematic immunosuppressant other than glucocorticoids within 30 days prior to enrollment.
- Patients with vaccination history within 30 days prior to screening.
- 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 by researchers.
- Patients with known planned major surgery schedule during the 52-week study period aren't eligible.
- 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. 10.Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.
Sites / Locations
- Institute of Hematology & Blood Diseases Hospital
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm of BBM 002
Arm Description
1×10^13 vg/kg, Single-dose treatment.
Outcomes
Primary Outcome Measures
Incidence of dose limiting toxicity (DLT) events
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) within 10 weeks after administration
The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
To assess the safety of BBM 002 Injection by TEAEs and SAEs
Secondary Outcome Measures
Full Information
NCT ID
NCT05454774
First Posted
July 7, 2022
Last Updated
July 7, 2022
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
1. Study Identification
Unique Protocol Identification Number
NCT05454774
Brief Title
A Study of FVIII Gene Therapy for Hemophilia A
Official Title
A Clinical Study of AAV Vector Expressing Human Coagulation Factor FVIII Gene Therapy for Hemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 15, 2022 (Anticipated)
Primary Completion Date
September 15, 2023 (Anticipated)
Study Completion Date
September 15, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a single-arm, open-label, clinical study to evaluate the safety, tolerability of BBM 002 injection in Hemophilia A subjects with residual factor VIII (FVIII) levels ≤2 International unit per deciliter (IU/dl) .
BBM 002 injection is an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor VIII (hFVIII) transgene and raises circulating levels of endogenous FVIII.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
Keywords
Hemophilia A; gene therapy; Adeno-Associated Virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
8 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Arm of BBM 002
Arm Type
Experimental
Arm Description
1×10^13 vg/kg, Single-dose treatment.
Intervention Type
Genetic
Intervention Name(s)
Single dose intravenous injection of BBM 002
Intervention Description
Single dose intravenous infusion of BBM 002, an adeno-associated virus (AAV) vector derived from recombinant DNA techniques to contain an expression cassette of the human factor VIII (hFVIII) transgene in liver. The dose of BBM 002 will be 1×10^13 vg/ kg
Primary Outcome Measure Information:
Title
Incidence of dose limiting toxicity (DLT) events
Description
To access the numbers of DLT events determined by the Safety Data Review Committee (SRC) within 10 weeks after administration
Time Frame
10 weeks
Title
The incidence of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs)
Description
To assess the safety of BBM 002 Injection by TEAEs and SAEs
Time Frame
52weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects are fully aware of the purpose, nature, methods and possible adverse reactions of the trial and voluntarily sign informed consent.
Males ≥ 18 years of age.
Have hemophilia A with ≤2 IU/dL (≤2 %) endogenous FVIII activity levels.
Have had ≥150 prior exposure days (EDs) to any recombinant and/or plasma-derived FVIII protein products.
Have had bleeding events and/or infusions with FVIII 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 FVIII or IV immunoglobulin administration.
Have no FVIII inhibitor. (eg <0.6BU/ml Bethesda Units; or the patient's FVIII inhibitor titer was detected <0.6BU/ml in 2 consecutive times within 1-4 weeks using Bethesda method or Nijmegen method), or no prior medical history of FVIII inhibitor after 150 EDs of FVIII products; no clinical signs or symptoms of decreased response to FVIII products infusion.
Agree to use a reliable barrier contraception method from the beginning of signing the informed consent to 52 weeks after BBM002 infusion.
Compliance is good, patients and their families have the will of 'gene therapy' clinical trials.
Exclusion Criteria:
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).
Currently on antiviral therapy for hepatitis B or C.
Patients with coagulation disorders in addition to hemophilia A.
Use of any other systematic immunosuppressant other than glucocorticoids within 30 days prior to enrollment.
Patients with vaccination history within 30 days prior to screening.
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 by researchers.
Patients with known planned major surgery schedule during the 52-week study period aren't eligible.
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. 10.Any concurrent clinically significant major disease or condition that the investigator deems unsuitable for participation in the study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Lei Zhang, MD
Phone
0086-22-23909095
Email
zhanglei1@ihcams.ac.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lei Zhang, MD
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences & Peking Union Medical College
Official's Role
Study Chair
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
12. IPD Sharing Statement
Plan to Share IPD
No
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A Study of FVIII Gene Therapy for Hemophilia A
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