Clinical trial: Emicizumab PUPs and Nuwiq ITI Study (NCT04030052)

Eligibility criteria:
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) or high titer inhibitor (>5
             BU/mL) with a 72-hour washout within 8 weeks of enrollment after either the first time
             ITI or after single attempt of <6 months of continuous 3x/week factor ITI

          -  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 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 not required if can demonstrate negative testing in 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 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 last drug
             administration; a non-hemophilia-related investigational drug concurrently, within
             last 30 days or 5 half-lives, whichever is shorter
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.

Subject must be at most 21 Years

Patient description (medical language): A 23-year-old female has prolonged oral bleeding immediately after a tooth extraction.  Despite several interventions, the bleeding persists for hours and stops only after desmopressin (DDAVP) administration.  The patient has heavy menstrual cycles each month.  She has no other medical problems and takes no medications.  Her mother and grandmother have also had excessive bleeding during menstrual period.  Review of systems is positive for mild bruising on his legs. Laboratory findings reveal a normal platelet count and an abnormal ristocetin cofactor assay, as well as CB <= 0.30 IU/mL and FVIII:C <= 0.40 IU/mL.

Patient description (patient's own words): I'm a 23 woman and I went to the ER because of non-stop bleeding after my tooth extraction. I tried to make the bleeding stop but it just kept going for hours and it finally stopped when I took some medication called DDAVP. I usually have heavy periods, just like my mom and grandma had. I don't have any other medical condition and I don't take any other medication. The doctor noticed the bruises on my legs. I had to do some lab tests. I had a normal platelet count but an abnormal ristocetin cofactor assay. I had low CB and FVIII:C levels.

Does the patient match the trial criteria? Entailment