Clinical trial
Clinical Exploration of Clinical Exploration Adeno-associated Virus Vector Expression of Human Coagulation Factor VIII Gene Therapy for Hemophilia A
Name
IHBDH-GTHA-2020
Description
IHBDH-GTHA-2020 is an open- label, non- randomized study to evaluate the safety, tolerability and kinetics of a single intravenous infusion of GS001 in hemophilia A subjects with \<1 IU/dl residual FVIII levels.
Trial arms
Trial start
2021-03-04
Estimated PCD
2028-07-31
Trial end
2028-07-31
Status
Recruiting
Treatment
Injection of GS001
Patients will be enrolled sequentially every 3 weeks or more between cohorts. 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 dose levels are as follows:
1. 2×10\^12 vg/kg
2. 6×10\^12vg/kg or other recommended doses
3. 2×10\^13 vg/kg or other recommended doses
Arms:
Treatment group
Size
12
Primary endpoint
Incidence of treatment- related adverse events
From screening through up to the end of study (about 5 years).
Percentage of subjects in each dose group with newly occurred clinically significant abnormalities in physical examination compared to the baseline.
From the start of study treatment (Day 1) through up to the end of study (about 5 years).
Changes of Weighted Mean of vital signs (systolic blood pressure [SBP] and diastolic blood pressure [DBP], pulse rate, temperature, respiratory rate) from baseline at each assessment time point for each dose group
From the start of study treatment (Day 1) through up to the end of study (about 5 years).
Changes of Mean Alkaline Phosphatase (ALP), Alanine Amino Transferase (ALT), Aspartate Amio Transferase (AST) from baseline at each assessment time point for each dose group
From the start of study treatment (Day 1) through up to the end of study (about 5 years).
Immune response to AAV capsid proteins
From screening period through up to 5 years.
Immune response to FVIII transgene
From screening period through up to 5 years.
Viral vector shedding of GS001
From date of infusion until the date of 3 consecutive documented negative results, assessed up to 1 year.
Thrombosis risk assessment
From the start of study treatment (Day 1) through up to the end of study (about 5 years).
Eligibility criteria
Inclusion Criteria:
1. Be able to understand the purpose and risks of the study and provide informed consent according to national and local privacy laws;
2. Male subjects and ≥ 18 years of age;
3. Have hemophilia A with ≤1 IU/dL (≤1%) endogenous FVIII activity levels at the time of screening. If the screening result is \>1% due to previous treatment with FVIII product, then it may be confirmed by documented historical evidence from a certified clinical laboratory demonstrating ≤1% FVIII activity levels ;
4. Have had ≥150 prior exposure days (EDs) to any recombinant and/or plasma-derived FVIII protein products;
5. Subjects have been on prophylactic exogenous FVIII therapy or on-demand exogenous FVIII therapy in the year prior to screening:
1. Prophylaxis subjects: Have had bleeding events during the last 12 weeks, as documented in the subjects' medical records; or
2. On-demand subjects: ≥ 3 bleeding episodes (spontaneous or traumatic) requiring exogenous FVIII therapy in the past 52 weeks;
6. No history of hypersensitivity or anaphylaxis associated with FVIII product administration;
7. Have no measurable FVII inhibitor as assessed by laboratory two times that were at least one week apart; or documented no prior history of FVIII inhibitor after 150 EDs and no clinical signs or symptoms of decreased response to FVIII infusion ;
8. Have acceptable laboratory values sampled at screening and repeated prior to Day 0; A. Hemoglobin ≥ 11 g/dL; B. Platelets ≥ 100 x 10\^9/L; C. AST, ALT, alkaline phosphatase ≤ 1.25 upper limit of normal (ULN); D. Bilirubin ≤ 1.25 ULN; E. Creatinine ≤ 2 mg/dL.
9. Agree to use reliable barrier contraception until the end of the 52 weeks observation period, and three consecutive semen samples are negative for vector sequences after GS001 infusion.
Exclusion Criteria:
1. Have Hepatitis B, hepatitis C or HBsAg, HCVAb, HBV-DNA, HCV-RNA are positive and have clinical significance. Both natural clearers and those who have cleared HCV on antiviral therapy are deemed eligible;
2. Currently Receiving antiviral therapy for hepatitis B and C;
3. Have underlying liver disease, as defined by previous diagnosis of portal hypertension, splenomegaly, hepatic encephalopathy, decrease of serum albumin and liver fibrosis ≥ 3 stage; or liver biopsy within the past 6 months confirmed METAVIR ≥ 3, FibroScan \> 8.3 kPa, Fibro Test/Fibro SURE \> 0.48, APRI \> 1; Subject has any confirmed congenital or acquired immunodeficiency diseases (e.g., various common type of immunodeficiency diseases, human immunodeficiency virus \[HIV\] infection, organ transplantation) ;
4. Have Anti-AAV8 neutralizing antibody titer ≥ 1:16, anti-AAV8 binding antibody titer ≥ 1:400;
5. Have history of chronic infections or other chronic diseases that may pose a risk to the study participation;
6. Have participated in a previous gene therapy research trial within the last 52 weeks or in a clinical study with an investigational drug within the past 30 days;
7. The subject has any concurrent diseases that cannot tolerate treatments of prednisone or prednisolone as judged by the investigator;
8. History of arterial or venous thromboembolic events (e.g., deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolism);
9. Known inherited or acquired thrombophilia, including conditions associated with increased risk of thromboembolism, such as atrial fibrillation;
10. Major surgery planned in 1 year period following the infusion with GS001;
11. Hypersensitivity to the study vector;
12. Have clinically major diseases or any other unspecified conditions that, in the opinion of the Investigator, makes the subject unsuitable for participating in the study;
13. Patients who are unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
14. Evidence of other bleeding disorders not associated with hemophilia A.
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['NA'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 12, 'type': 'ESTIMATED'}}
Updated at
2023-05-19
1 organization
1 product
2 indications
Product
GS001Indication
Hemophilia AIndication
Gene Therapy