Clinical trial: A Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Emicizumab in Participants From Birth to 12 Months of Age With Hemophilia A Without Inhibitors (NCT04431726)

Eligibility criteria:
Inclusion Criteria:

          -  Age from birth to ≤12 months at time of informed consent

          -  Body weight ≥3 kilograms (kg) at time of informed consent. Patients with a lower body
             weight can be enrolled after they have reached a body weight of 3 kg. Premature babies
             (gestational age <38 weeks) may be enrolled as long as they have reached a body weight
             of 3 kg. For premature babies, the corrected gestational age should be reported.

          -  Mandatory receipt of vitamin K prophylaxis according to local standard practice

          -  Diagnosis of severe congenital hemophilia A (intrinsic FVIII level <1%)

          -  A negative test for FVIII inhibitor (i.e., <0.6 Bethesda units [BU]/mL) locally
             assessed during the 2-week screening period

          -  No history of documented FVIII inhibitor (i.e., <0.6 BU/mL), FVIII drug-elimination
             half-life <6 hours, or FVIII recovery <66%

          -  Previously untreated patients or minimally treated patients (i.e., up to 5 days of
             exposure with hemophilia-related treatments, such as plasma-derived FVIII, recombinant
             FVIII, fresh frozen plasma, cryoprecipitate, or whole blood products)

          -  Documentation of the details of the hemophilia-related treatments received since birth

          -  Documentation of the details of the bleeding episodes since birth

          -  For patients from birth to <3 months of age at the time of study entry: no evidence of
             active intracranial hemorrhage, as confirmed by a negative cranial ultrasound at
             screening irrespective of delivery mode

          -  Adequate hematologic, hepatic, and renal function, as defined in the protocol

          -  For parents/caregivers: willingness and ability to comply with the study protocol
             requirements, scheduled visits, treatment plans, laboratory tests, completion of
             applicable questionnaires, and other study procedures

        Exclusion Criteria:

          -  Inherited or acquired bleeding disorder other than severe hemophilia A

          -  Use of systemic immunomodulators (e.g., interferon) at enrollment or planned use
             during the study

          -  Receipt of any of the following: An investigational drug to treat or reduce the risk
             of hemophilic bleeds within 5 drug-elimination half-lives of last drug administration;
             A non-hemophilia-related investigational drug within the last 30 days or 5
             drug-elimination half-lives, whichever is shorter; An investigational drug
             concurrently

          -  Current active severe bleed, such as intracranial hemorrhage

          -  Planned surgery (excluding minor procedures, e.g., circumcision, CVAD placement)
             during the study

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

          -  Patients who are at high risk for thrombotic microangiopathy (TMA) (e.g., have a
             previous medical or family history of TMA, such as thrombotic thrombocytopenic
             purpura, atypical hemolytic uremic syndrome) in the investigator's judgment

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

          -  Any hereditary or acquired maternal condition that may predispose the patient to
             thrombotic events (e.g., inherited thrombophilias antiphospholipid syndrome)

          -  Other diseases (e.g., certain autoimmune diseases) that may increase risk of bleeding
             or thrombosis

          -  Known infection with HIV, hepatitis B virus, or hepatitis C virus

          -  Serious infection requiring antibiotics or antiviral treatments within 14 days prior
             to screening

          -  Concurrent disease, treatment, abnormality in clinical laboratory tests, vital signs
             measurements, or physical examination findings that could interfere with the conduct
             of the study or that would, in the opinion of the investigator or Sponsor, preclude
             the patient's safe participation in and completion of the study or interpretation of
             the study results

          -  Unwillingness of the parent or caregiver to allow receipt of blood or blood products,
             or any standard-of-care treatment for a life-threatening condition

          -  Any other medical, social, or other condition that may prevent adequate compliance
             with the study protocol in the opinion of the investigator
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.

Subject must be at most 12 Months

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