Brief Title
Gene Therapy for Chinese Hemophilia A
Official Title
Gene Therapy for Chinese Hemophilia A With Adeno-associated Virus (AAV) Vector
Brief Summary
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.
Detailed Description
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.
Study Type
Interventional
Primary Outcome
Incidence of treatment- related adverse events
Secondary Outcome
Vector- derived FVIII:C and FVIII antigen levels
Condition
Hemophilia A
Intervention
Injection of GS001
Study Arms / Comparison Groups
Treatment group
Description: Arm of GS001
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Genetic
Estimated Enrollment
3
Start Date
March 4, 2021
Completion Date
July 31, 2023
Primary Completion Date
July 31, 2023
Eligibility Criteria
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.
Gender
Male
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Lei Zhang, MD, +82223909240, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT04728841
Organization ID
IHBDH-GTHA-2020
Responsible Party
Principal Investigator
Study Sponsor
Institute of Hematology & Blood Diseases Hospital
Study Sponsor
Lei Zhang, MD, Principal Investigator, Chinese Academy of Medical Science and Blood Disease Hospital
Verification Date
September 2022