Open-Label Single Ascending Dose of Adeno-associated Virus Serotype 8 Factor IX Gene Therapy in Adults With Hemophilia B
Study Details
- Hemophilia B
- Biological: AskBio009
- Inclusion Criteria:
- Males age 18-75 years, inclusive
- Established hemophilia B with ≥3 hemorrhages per year requiring treatment with exogenous FIX OR use of FIX prophylaxis because of history of frequent bleeding episodes
- Plasma FIX activity ≤2% (\<1% for first cohort; then per protocol)
- Negative for active Hepatitis C virus (HCV), defined as Hepatitis C virus antibody negative and negative (undetectable) PCR test for plasma Hepatitis C virus ribonucleic acid (RNA) OR if Hepatitis C virus antibody positive must have ≥2 consecutive negative (undetectable) PCR tests for plasma HCV RNA at least 3 months apart, and negative at screening
- Exclusion Criteria:
- Family history of inhibitor to FIX protein or personal laboratory evidence of having developed inhibitors to FIX protein at any time (\>0.6 Bethesda Units on any single test)
- Documented prior allergic reaction to any FIX product
- Detectable AAV8 neutralizing antibodies
- Markers of hepatic inflammation or overt or occult cirrhosis as evidenced by one or more of the following:
- Platelet count \<175,000/μL
- Albumin ≤3.5 g/dL
- Total bilirubin \>1.5 x ULN and direct bilirubin ≥0.5 mg/dL
- Alkaline phosphatase \>2.0 x ULN
- ALT or AST \>2.0 x ULN (except for subjects who are HIV infected)
- Liver biopsy in the past indicating moderate or severe fibrosis (Metavir staging of 2 or greater)
- History of ascites, varices, variceal hemorrhage or hepatic encephalopathy
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.