Gene Therapy for Chinese Hemophilia A
Study Details
- Hemophilia A
- Ignored
- Be able to understand the purpose and risks of the study and provide informed consent according to national and local privacy laws;
- Male subjects and ≥ 18 years of age;
- 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 ;
- Have had ≥150 prior exposure days (EDs) to any recombinant and/or plasma-derived FVIII protein products;
- Subjects have been on prophylactic exogenous FVIII therapy or on-demand exogenous FVIII therapy in the year prior to screening:
- Prophylaxis subjects: Have had bleeding events during the last 12 weeks, as documented in the subjects' medical records; or
- On-demand subjects: ≥ 3 bleeding episodes (spontaneous or traumatic) requiring exogenous FVIII therapy in the past 52 weeks;
- No history of hypersensitivity or anaphylaxis associated with FVIII product administration;
- 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 ;
- 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.
- 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.
- 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;
- Currently Receiving antiviral therapy for hepatitis B and C;
- 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) ;
- Have Anti-AAV8 neutralizing antibody titer ≥ 1:16, anti-AAV8 binding antibody titer ≥ 1:400;
- Have history of chronic infections or other chronic diseases that may pose a risk to the study participation;
- 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;
- The subject has any concurrent diseases that cannot tolerate treatments of prednisone or prednisolone as judged by the investigator;
- History of arterial or venous thromboembolic events (e.g., deep vein thrombosis, non-hemorrhagic stroke, pulmonary embolism, myocardial infarction, arterial embolism);
- Known inherited or acquired thrombophilia, including conditions associated with increased risk of thromboembolism, such as atrial fibrillation;
- Major surgery planned in 1 year period following the infusion with GS001;
- Hypersensitivity to the study vector;
- 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;
- Patients who are unable or unwilling to comply with the schedule of visits and study assessments described in the clinical protocol;
- Evidence of other bleeding disorders not associated with hemophilia A.
Protocol Summary
This study is looking at how safe it is to switch from emicizumab to Mim8, in people with haemophilia A. Mim8 is a new medicine that is used to prevent bleeding episodes in people with haemophilia A. Mim8 works by replacing the function of the missing clotting factor VIII (FVIII). Mim8 will be injected under the skin using a pen-injector either once every week, once every two weeks or once every month. The participants will be trained in using the pen injector. The participants can choose themselves, in collaboration with the study doctor how often they get Mim8 in this study. When the participant will get their first Mim8 injection depends on their current treatment with emicizumab. The participants will get their first Mim8 injection at Visit 2. Participants will have between 6 and 27 Mim8 injections. The total number of injections participants will have depends on their dosing frequency. The study will last for about 6-12 months. While taking part in this study, there are some restrictions about what medicine participant can use. The study doctor will tell the participants more about this. In case the participants experience bleeds, these can be treated with additional haemostatic medicine as agreed with the study doctor. Female participants cannot take part if they are pregnant, breast-feeding or plan to get pregnant during the study period.