Gene Therapy for Chinese Hemophilia A
Gene Therapy for Chinese Hemophilia A With Adeno-associated Virus (AAV) Vector
GS001 is an open- label, non- randomized, uncontrolled study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of GS001 in hemophilia A subjects with <1IU/dl residual FVIII levels.
GS001 is a open- label, non- randomized, uncontrolled, study to evaluate the safety, tolerability and kinetics of GS001 in hemophilia A subjects with residual FVIII levels<1IU/dl. Three patients will be enrolled sequentially every 3 weeks or more between cohorts and administered with single infusion of GS001.Dose escalation may occur after a single patient has been safely dosed if the resulting FVIII activity at Week 3 is < 5 IU/dL.The dosing to the second subject will not be performed until acquiring the approve from independent safety committee.The dose levels are as follows: 1. 2×10^12 vg/kg 2. 6×10^12 vg/kg 2. 2×10^13 vg/kg Subjects will provide informed consent and then undergo screening assessments up to 4-8weeks prior administration of GS001. All subjects will undergo 52(+- 2) weeks safety observation.
Incidence of treatment- related adverse events
Vector- derived FVIII:C and FVIII antigen levels
Injection of GS001
Study Arms / Comparison Groups
Description: Arm of GS001
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
March 4, 2021
July 31, 2023
Primary Completion Date
July 31, 2023
Inclusion Criteria: - 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; - Endogenous FVIII activity levels<1iu. as documented by a certified clinical laboratory at the time of screening. - Prior FVIII exposure days (EDs) ≥150 days of any recombinant and/or plasma-derived FVIII protein products based on historical data from the subject's record/history; - A. Prophylaxis subjects: have had bleeding events and/or infusions with FVIII protein products during the last 12 weeks documented in the subjects' medical records; 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 FVIII or IV immunoglobulin administration; - Have no measurable FVIII inhibitor as assessed by laboratory; or documented no prior history of FVIII inhibitor after 150 EDs (family history of inhibitors will not exclude the subject) and no clinical signs or symptoms of decreased response to FVIII administration; - Have acceptable laboratory values: Hemoglobin ≥11 g/dL; Platelets ≥100,000 cells/μL; Aspartate Transaminase（AST）, alanine aminotransferase （ALT）, alkaline phosphatase ≤1.25x upper limit of normal at the testing laboratory; Bilirubin ≤1.25x upper limit of normal（ULN）; Creatinine ≤2.0 mg/dL. • Agree to use reliable barrier contraception until three consecutive semen samples after the administration of GS001 are negative for vector sequences. Exclusion Criteria: - HBsAg or hepatitis B core antibody or hepatitis B virus-DNA positivity or hepatitis C virus-RNA viral load positivity. Negative viral assays in two samples, collected at least six months apart, will be required to be considered negative. Both natural clearer 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; - Anti-GS001 neutralizing antibody titers ≥1:16, anti-GS001 antibody titers ≥1:400; - History of chronic infection or other chronic disease that the Investigator considers to constitute an unacceptable risk; - 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; - Bad compliance.
18 Years - N/A
Accepts Healthy Volunteers
Lei Zhang, MD, +82223909240, [email protected]
Institute of Hematology & Blood Diseases Hospital
Lei Zhang, MD, Principal Investigator, Chinese Academy of Medical Science and Blood Disease Hospital