Individualizing Hemophilia Prophylaxis Using Thromboelastography

This is a pilot study in children and adults with severe hemophilia A that utilizes the TEG/ROTEM to personalize their prophylaxis treatment.

Primary objectives:

• Assess the feasibility of TEG/ROTEM-guided modification of the current prophylaxis regimen for individuals with severe hemophilia A. Specifically, to:

• Test and refine the operational protocol for using TEG/ROTEM to guide factor dosing
• Estimate the proportion of hemophilia A patients whose dose will be modified based on TEG/ROTEM results
• Monitor short term safety of patients whose dose has been modified.

Secondary objectives

• Perform thrombin generation assays to provide additional evidence supporting the TEG/ROTEM-guided dosing.
• Obtain preliminary data on the economic impact of TEG/ROTEM-guided hemophilia A dosing regimens.
• Obtain preliminary data on the potential improvement of subject/family burden resulting from TEG/ROTEM-guided regimen using generic and specific quality of life tools.

The study period will consist of screening, pharmacokinetic (PK) study and follow-up. For subjects whose prophylaxis treatment regimen is modified, the follow-up period will include 3 follow-up clinic visits and 4 follow-up phone calls; these patients will remain on study for approximately 6 months following completion of the PK-study then will have an end of the study visit (visit 9). Subjects whose treatment regimen is not altered will end their study participation after Visit 2 and continuing with their current prophylaxis regimen.

Study endpoints: A safety review will be conducted after the first 6 subjects complete 30 days with the extended prophylaxis treatment. If no safety issues are identified, the study will proceed, and second safety review will be after an additional 8 subjects complete 30 days of extended treatment. If a subject has two or more spontaneous bleeds in 30 days, the subject will be removed from the study. For subjects who did not have bleeds and completed at least 6 months of the study, ongoing prophylactic treatment will be decided by their treating physician.

Inclusion criteria

• Males, 5-70 years, inclusive
• Plasma FVIII activity <1% documented (Laboratory result or MD documentation of Severe Hemophilia A diagnosis)
• Currently prescribed prophylaxis treatment regimen infusing ≥3 times a week
• Willing to alter their prophylaxis treatment regimen per study protocol

Exclusion criteria

• Bleeding disorder(s) other than Hemophilia A
• Current inhibitor (>0.6BU)
• Thrombocytopenia (platelet count <100,000K/µL since it can alter TEG®/ROTEM® results)
• Creatinine >2x the upper limit of normal (indicating potential platelet dysfunction)
• Prothrombin time >3 seconds above the upper limit of normal (indicating potential liver dysfunction)
• Any concurrent clinically significant major disease, frequent bleeding pattern or history of non-compliance that, in the opinion of the investigator, would make the subject unsuitable for enrollment
• Participation within the past 30 days in any other clinical study involving investigational drugs
• Planned major surgery within 30 days prior to screening or during the study period
• Current use of any medication known to have effects on the coagulation system