Clinical trial: Efficacy, Safety, and Pharmacokinetic Study of Prophylactic Emicizumab Versus No Prophylaxis in Hemophilia A Participants (NCT03315455)

Eligibility criteria:
Inclusion Criteria:

        Inclusion Criteria for Arms A, B, and C:

          -  Diagnosis of severe congenital hemophilia A or hemophilia A with FVIII inhibitors

          -  Aged 12 years or older at the time of informed consent

          -  Body weight ≥40 kilograms (kg) at the time of screening

          -  Participants without FVIII inhibitors (<0.6 Bethesda unit per milliliter [BU/mL]) who
             completed successful immune tolerance induction (ITI) must have done so at least 5
             years before screening and have no evidence of inhibitor recurrence (permanent or
             temporary)

          -  Documentation of the details of episodic therapy (FVIII or bypassing agents) and of
             number of bleeding episodes for at least the last 24 weeks and ≥5 bleeds in the last
             24 weeks prior to study entry

          -  Adequate hematologic, hepatic, and renal function

          -  For women of child bearing potential: agreement to remain abstinent or use a protocol
             defined contraceptive measure during the treatment period and for at least 5
             elimination half-lives (24 weeks) after the last dose of study drug

        Inclusion Criteria for Arm D:

          -  Diagnosis of congenital hemophilia A of any severity and documented history of
             high-titer inhibitor (i.e., ≥5 BU/mL)

          -  Children <12 years old at time of informed consent

          -  Body weight >3 kg at time of informed consent

          -  Requires treatment with bypassing agents

          -  Adequate hematologic, hepatic, and renal function

          -  For female participants who are of childbearing potential, follow the same
             contraception criteria as listed above for Arms A, B, and C

        Exclusion Criteria:

        Exclusion Criteria for Arms A, B, and C:

          -  Inherited or acquired bleeding disorder other than hemophilia A

          -  At high risk for thrombotic microangiopathy, in the investigator's judgment

          -  History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the
             investigator's judgment

          -  Previous (in the past 12 months) or current treatment for thromboembolic disease (with
             the exception of previous catheter-associated thrombosis for which anti-thrombotic
             treatment is not currently ongoing) or signs of thromboembolic disease

          -  Other conditions that may increase risk of bleeding or thrombosis

          -  History of clinically significant hypersensitivity associated with monoclonal antibody
             therapies or components of the emicizumab injection

          -  Known human immuno-deficiency virus (HIV) infection with cluster of differentiation 4
             (CD4) count <200 cells/microliter (cells/mcL) within 24 weeks prior to screening.
             Participants with HIV infection who have CD4 >200 cells/mcL and meet all other
             criteria are eligible

          -  Use of systemic immunomodulators at enrollment or planned use during the study, with
             the exception of anti-retroviral therapy

          -  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 such as tooth extraction or incision and
             drainage) during the study

          -  Receipt of: Emicizumab in 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

          -  Pregnant or lactating, or intending to become pregnant during the study

        Exclusion Criteria for Arm D:

          -  Inherited or acquired bleeding disorder other than hemophilia A

          -  Ongoing (or plan to receive during the study) ITI therapy or prophylaxis treatment
             with FVIII

          -  Previous (in the past 12 months) or current treatment for thromboembolic disease (with
             the exception of previous catheter-associated thrombosis for which anti-thrombotic
             treatment is not currently ongoing) or signs of thromboembolic disease

          -  Other diseases that may increase risk of bleeding or thrombosis

          -  History of clinically significant hypersensitivity associated with monoclonal antibody
             therapies or components of the emicizumab injection

          -  Known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV)

          -  At high risk for thrombotic microangiopathy, in the investigator's judgment

          -  Use of systemic immunomodulators at enrollment or planned use during the study

          -  Planned surgery (excluding minor procedures such as tooth extraction or incision and
             drainage) during the study

          -  Inability (or unwillingness by caregiver) to receive (allow receipt of) blood or blood
             products (or any standard-of-care treatment for a life-threatening condition)

          -  Receipt of: Emicizumab in 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

          -  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

          -  Pregnant or lactating, or intending to become pregnant during the study
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.



Patient description (medical language): A 20-year-old man comes to the emergency due to bleeding after a tooth extraction.  The bleeding has persisted for approximately 30 minutes despite constant direct pressure.  He is a known case of Hemophilia type A treated with FVIII. Blood pressure is 95/60 mm Hg and pulse is 105/min. His weight is 70 Kg. Family history is positive for Hemophilia type A in his maternal uncle. He also has a lipoma on his left arm which he plans to remove surgically. His FVIII activity is 40%.

Patient description (patient's own words): I got my tooth extracted and I could not stop bleeding for 30 min. I'm a 20 yo dude but I have Hemophilia type A treated with FVIII. My blood pressure was 95/60 and my pulse 105/min. I'm 70 kg. My uncle on my mom's side also has type A hemophilia. I also have a fatty swelling on my left arm and I was supposed to remove it. My FVIII activity was 40%.

Does the patient match the trial criteria? Contradiction