Rituximab to Treat Severe Hemophilia A (RICH)

• Proportion of participants in which the inhibitor level falls to less than 5 BU/mL between Weeks 6 to 22 and remains below 5 BU/mL at 5 to 7 days following re-challenge with factor VIII [ Time Frame: Measured within approximately 22 weeks ] [ Designated as safety issue: No ]
  

• Proportion of participants in which inhibitor level falls to less than 5 BU/mL between Weeks 6 to 22 and anamnestic peak following factor VIII re-challenge is 5 to 10 BU/mL and less than 50% of original peak [ Time Frame: Measured within approximately 22 weeks ] [ Designated as safety issue: No ]
  
• Percentage change in inhibitor titer on challenge with factor VIII from baseline challenge to post-treatment challenge [ Time Frame: Measured within approximately 22 weeks ] [ Designated as safety issue: No ]
  
• Safety of rituximab in participants with severe hemophilia A and high responding inhibitors [ Time Frame: Measured through Week 100 ] [ Designated as safety issue: Yes ]
  

Hemophilia A is a hereditary blood clotting disorder. It is caused by a deficiency or abnormality of the blood clotting protein factor VIII. Individuals with hemophilia A are unable to form blood clots to stop bleeding and are at risk for experiencing serious and life-threatening bleeding episodes. The most common treatment for this disease is intravenous replacement of factor VIII at the start of a bleeding episode. However, between 30 to 40% of individuals eventually develop inhibitors, or antibodies, to the replacement factor. In these individuals, the immune system recognizes the replacement factor as foreign and attacks it, thereby countering any potential benefits of the treatment. Some individuals with severe hemophilia A may undergo immune tolerance therapy (ITT), in which they receive replacement factor on a regular basis as a way for the body to adjust to the factor and stop inhibitor production. This treatment, however, is not always effective for everyone. Preliminary research has shown that rituximab, a medication used to treat non-Hodgkin's lymphoma, may be successful in suppressing or eliminating the inhibitors that develop. The purpose of this study is to evaluate the effectiveness of rituximab at lowering the levels of factor VIII inhibitors in individuals with severe hemophilia A.

This study will enroll individuals with severe hemophilia A. At study entry, participants will receive one intravenous dose of factor VIII. Inhibitor levels will be measured with a blood test 5 to 7 days following this procedure. If peak inhibitor level is above 5 Bethesda units (BU)/mL, 5 to 9 days later participants will begin receiving rituximab intravenously once a week for 4 weeks. Blood will be collected at each visit for laboratory testing. Two weeks following the last rituximab treatment, participants will have blood drawn for inhibitor testing; this testing will occur every 4 weeks through Week 22. If the participant's inhibitor level falls below 5 BU/mL, participants will receive a repeat dose of factor VIII, and blood will be drawn 5 to 7 days later for inhibitor testing. Follow-up visits will occur at Weeks 36, 52, and 100, and will include a physical examination, blood collection, and monitoring of bleeding events and infections. Telephone interviews will be conduced at Weeks 64, 76, and 88 to monitor bleeding events and infections.