Emicizumab PUPs and Nuwiq ITI Study
Study Details
- Hemophilia A
- Drug: Nuwiq (low dose protocol)
- Drug: HEMLIBRA
- Drug: Nuwiq (Atlanta protocol)
- Inclusion Criteria - Part A:
- Moderately severe (≤2% FVIII) hemophilia A
- <3 Years of age at the time of informed consent
- Caregiver (parent or legal guardian) has provided written informed consent
- ≤2 EDs to pdFVIII, rFVIII, or a single dose of FFP, Cryoprecipitate or PRBCs.
- Adequate hematologic function (HgB >8 g/dL and platelet count >100,000 µL)
- Adequate hepatic function (total bilirubin ≤1.5x ULN and both AST/ALT ≤3x ULN at screening (excluding known Gilbert's)
- Adequate renal function (≤2.5 x ULN and CrCl ≥30 mL/min)
- Negative test for inhibitor (<0.6 BU/mL) with a 72-hour washout within 4 weeks of enrollment
- No documented FVIII inhibitor since birth *Participants will be encouraged to co-enroll in the ATHN 8 Study
- Inclusion Criteria - Part B
- Moderately severe (≤2% FVIII) hemophilia A
- <21 Years of age at the time of informed consent
- Documented on 2 occasions a persistent low (>0.6 BU/mL) titer inhibitor with a 72-hour washout within 24 weeks of enrollment or historical high titer inhibitor (>5 BU/mL) and a single occasion of a low titer inhibitor (>0.6 BU/mL) with a 72-hour washout within 24 weeks of enrollment after either the first time ITI or after single attempt of <6 months of continuous 3x/week factor ITI
- Has completed loading doses of HEMLIBRA® (weekly for 4 weeks, dose 3 mg/kg, a total of 12 mg/kg/dose will also be allowed)
- Caregiver and/or participant provided written informed consent
- Adequate hematologic function (HgB >8 g/dL and platelet count >100,000 µL)
- Adequate hepatic function (total bilirubin ≤1.5x ULN and both AST/ALT ≤3x ULN at screening (excluding known Gilbert's)
- Adequate renal function (≤2.5 x ULN and CrCl ≥30 mL/min)
- Exclusion Criteria - Part A and B
- Inherited or acquired bleeding disorder other than severe hemophilia A (participants with previous documentation of low von Willebrand factor (vWF) defined as vWF antigen and vWF ristocetin cofactor both between 40-50 will be permitted)
- Previous or current treatment for thromboembolic disease or signs of thromboembolic disease
- Conditions that may increase the risk of bleeding or thrombosis. Will not require or request a thrombophilia evaluation
- History of clinically significant hypersensitivity associated with monoclonal antibody therapies or components of the HEMLIBRA® injection (with the exception of rituximab)
- Known HIV infection with CD4 count <200 cells/µL within 24 weeks prior to screening. Testing is not required if can demonstrate negative testing in the mother prior to pregnancy
- Use of systemic immunomodulators at enrollment or planned use during the study
- Participants who are at high risk for thrombotic microangiopathy (TMA) (for example, have a previous medical or family history of TMA), in the investigator's judgment
- Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study, may pose an additional risk, or would, in the opinion of the investigator, preclude the participant's safe participation in and completion of the study
- Planned surgery (excluding minor procedures or central line placement) during the study
- Receipt of HEMLIBRA® as part of a prior investigational study; an investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of the last drug administration; a non-hemophilia-related investigational drug concurrently, within the last 30 days or 5 half-lives, whichever is shorter
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.