Comparing 6 approaches for hemophilia a

Exclusion

• −History of clinically significant allergies
• −History of severe allergic or anaphylactic reactions to monoclonal antibody therapy and to chimeric or humanized antibodies or fusion proteins
• −Known hypersensitivity to Chinese hamster ovary cell products or to excipient content
• −i) An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration or normalization of targeted parameters (e.g., anti-thrombin), whichever is longer; ii) A non-hemophilia-related investigational drug within last 30 days or 5 half-lives, whichever is shorter; iii) Any other investigational drug currently being administered or planned to be administered; iv) Prior gene therapy or gene therapy planned to be administered; v) Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollmentEnrolmentThe number of participants a study plans to include, or has included.Read more → or planned use during the study, with the exception of anti-retroviral therapy to treat HIV.
• −Known HIV infection with CD4 counts \<200 cells/μL
• −Inherited or acquired bleeding disorders other than congenital hemophilia A
• −Ongoing or planned ITI therapy
• −Previous 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
• −At high risk for thrombotic microangiopathy (TMA), including past personal or family history of TMA, in the investigatorPrincipal investigatorThe doctor or researcher responsible for running the study at a site.Read more →'s judgment
• −For Part 1 only: Personal history of ischemic heart disease, cerebrovascular disease, or diabetes mellitus
• −For Part 1 only: Strong family history of ischemic heart disease or cerebrovascular disease (i.e., first degree relatives such as parents, full siblings, or children): male relatives diagnosed under the age of 55 years and females under the age of 65 years
• −For Part 1 only: Previous or concomitant malignancies or leukemia
• −Other conditions (e.g., autoimmune conditions such as Systemic Lupus erythematosus and other systemic inflammatory disorders) that may currently increase the risk of bleeding or thrombosis
• −Receipt of any of the following:
• −Protein C activity, protein S free antigen, or anti-thrombin III activity levels below the lower limit of the reference range at screeningScreeningThe checks done before joining, to see whether a study fits.Read more →
• −History or presence of an abnormal ECG that is deemed clinically significant, (e.g., complete left bundle branch block, second- or third -degree atrioventricular heart block), including atrial fibrillation or evidence of prior myocardial infarction
• −QT interval corrected through use of Fridericia's formula (QTcF) \>450 ms demonstrated by at least two ECGs \>30 minutes apart
• −History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome
• −Current treatment with medications that are well known to prolong the QT interval