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