Hematopoietic Stem Cell Transplantation Gene Therapy for Treatment of Severe Hemophilia A
Study Details
- Hemophilia A
- Biological: Auto CD34+PBSC transduced with a lentiviral vector encoding a novel coagulation factor VIII transgene
- Able to provide informed consent for the protocol approved by the Institutional Review Board.
- Male subjects who are ≥18 years of age and \< 45 years of age.
- Diagnosis of severe hemophilia A (\<1 IU/dl factor VIII activity).
- Documented history of more than 100 exposures of factor VIII treatment.
- Average of at least 3 bleeds requiring treatment per year over the prior three years, at least 3 bleeds per year during the 3 years preceding the initiation of prophylaxis, or evidence of joint damage (knee, elbow or ankle) on physical or radiographic examination thought to be related to hemophilia.
- Performance status (Karnofsky score) of at least 70.
- Willing and able to comply with the requirements of the protocol.
- History of spontaneous central nervous system bleeding within the last 5 years.
- Significant organ dysfunction which could interfere with outcome of therapy such as: -
- Cardiac: There should be no evidence of significant cardiac dysfunction (resting left ventricular ejection fraction of \< 50%) and no cardiomegaly. There should not be uncontrollable hypertension.
- Renal: Glomerular Filtration Rate (GFR) \< 60 ml/min/1.73m2 as calculated using the Cockcroft-Gault equation.
- Hepatic: There should be no evidence of hepatic dysfunction which is defined as a serum bilirubin of \> 1.5 mg/dl and Aspartate Amino Transferase (AST) / Alanine Amino Transferase (ALT) \> 3X the upper limit of normal,
- Hematologic: Absolute neutrophil counts (ANC) \< 1000/mm3 and platelets counts \< 150,000/μL.
- Pulmonary function with a corrected Diffusing Capacity of lung for Carbon Monoxide (DLCO) of \< 50% predicted
- History of a FVIII inhibitor (\>0.6 Bethesda Units/ml) including at least 2 measurements over the preceding 5 years or any single titer \>5 Bethesda Units (BU) /ml.
- Previous stem cell transplant.
- HIV positive.
- Evidence of hepatitis B active infection or chronic carrier
- Evidence of chronic hepatitis C infection. Absence of chronic infection will be documented with at least 2 negative viral loads at least 6 months apart.
- Diagnosis of a bleeding disorder other than hemophilia A
- Use of medication(s) that can affect hemostasis (e.g. aspirin and non- cyclooxygenase (COX-2) selective non-steroid anti-inflammatory drugs).
- History of cancer or familial cancer syndromes
- Any condition in the opinion of the principle investigator that will negatively impact the subject's ability to safely undergo an autologous stem cell transplant.
- Any reason in the opinion of the principle investigator that will negatively impact the subject's ability to complete the clinical trial per the trial protocol.
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.