Multiple Escalating Dose Study of BAY1093884 in Adults With Hemophilia A or B With or Without Inhibitors

Multiple Escalating Dose Study of BAY1093884 in Adults With Hemophilia A or B With or Without Inhibitors

The purpose of this study was to assess the safety and tolerability of multiple doses of a human monoclonal antibody (BAY1093884) given under the skin in subjects with hemophilia A or B. This antibody was intended to protect from bleeds by inhibiting a substance (Tissue Factor Pathway Inhibitor, TFPI) that reduces the ability of the body to form blood clots.

The primary objective of the study was to assess the safety and tolerability of multiple subcutaneous injections of BAY1093884 (anti-TFPI monoclonal antibody, immunoglobulin G2, IgG2) in patients with hemophilia A or B with or without inhibitors.

Inclusion Criteria:

• Male severe hemophilic patients with undetectable FVIII activity <1% or FIX activity <2%, with or without inhibitors (any titer) are eligible.
• Subjects with a past history of inhibitors (any inhibitor titer) are eligible.
• Age ≥18 years.
• Documentation of ≥4 bleeding episodes (any type or location of bleeds, treated or not) within the 6 months prior to screening.
• For subjects on prophylaxis: Willingness to interrupt ongoing prophylaxis.
• For subjects on immune tolerance induction (ITI): Willingness to interrupt ongoing ITI.

Exclusion Criteria:

• History of any other coagulation disorder (particularly disseminated intravascular coagulopathy or combined FVIII/FV deficiency) or platelet disorder.
• History of diseases related to venous thromboembolic events (e.g., pulmonary embolism, deep vein thrombosis, thrombophlebitis) or thrombotic microangiopathy.
• Risk factors for venous or arterial diseases (e.g., uncontrolled hypertension, uncontrolled diabetes).
• History of cardiac, coronary and/or arterial peripheral atherosclerotic disease
• Platelet count <100,000/μL.
• Human immunodeficiency virus (HIV) infection with a cluster of differentiation 4 (CD4+) lymphocyte count of <200/mm^3