Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Congenital Hemophilia A

Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (OBI-1) in the Treatment of Patients With Congenital Hemophilia A With Factor VIII Inhibitors

This study is to test whether the study drug (OBI-1) is safe and effective for the treatment of serious bleeding episodes in people with congenital hemophilia A.

Inclusion Criteria:

• Written informed consent/assent from participant and/or participant's parent or legal representative.

• Participants with congenital hemophilia A with human factor VIII inhibitor ≤30 BU assessed within 90 days prior to study entry.

• Has previously or is currently demonstrating suboptimal hemostatic response to bypassing agents for treatment of bleeding episodes; suboptimal response is determined by the investigator , but minimally includes no or minimal evidence of response after at least two doses of bypassing agents, either for the current or a historic bleeding episode.

• Has an anti-OBI-1 titer ≤ 10 BU

• Has any serious or life-threatening bleeding episode; or requires a surgical procedure that could lead to a serious bleeding episode if not well controlled.

• Is willing and able to follow all instructions and attend all study visits.

• Has no other significant hemostatic abnormality and:

  • Platelets ≥100,000/mm-cubed
  • Prothrombin time < 15 seconds
  • INR < 1.3

• Participants taking anti-thrombotics (such as clopidogrel, heparin or heparin analogue) may be included provided three half-lives of the agent have elapsed since the last dose of the agent.

Exclusion Criteria:

• Hemodynamically unstable after blood transfusion, fluid resuscitation and pharmacologic or volume replacement pressor therapy. This hemodynamic instability is characterized by symptomatic hypotension resulting in vital organ dysfunction, such as cardiac ischemia, oliguria (urine volume <0.5 mL/kg in the previous six hours), central nervous system hypoperfusion manifested by mental status change such as confusion (unless head injury or intracranial hemorrhage is present), pulmonary compromise, and/or acidosis (manifested by pH and lactate levels).
• Bleeding episode assessed likely to resolve on its own if left untreated.
• Use of hemophilia medication: recombinant factor VIIa within 3 hours prior to OBI-1 administration or activated prothrombin complex concentrate (aPCC) treatment within 6 hours prior to OBI-1 administration
• Prior history of bleeding disorder other than congenital hemophilia A
• Known major sensitivity (anaphylactoid reactions) to porcine or hamster products. Examples include therapeutics of porcine origin (e.g. previously marketed porcine factor VIII, Hyate-C®) and recombinant therapeutics prepared from hamster cells (e.g. Humira®, Advate® and Enbrel®).
• Received any other investigational treatment within 30 days of the first OBI-1 treatment.
• Anticipated need for treatment or device during the study that may interfere with the evaluation of the safety or efficacy of OBI-1, or whose safety or efficacy may be affected by OBI-1.
• Is planning to father a child during the study
• Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the participant's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
• Inability or unwillingness to comply with the study design, protocol requirements, or the follow-up procedures.