Joint Health Study

This is a prospective, non-randomized, controlled study to examine whether or not having a
higher trough during prophylactic treatment with clotting factor offers better joint
protection than the standard trough of 1% Factor IX (FIX or Factor 9). This study will test
the hypothesis that an extended half-life (EHL) FIX product with an intended trough of >10%
could offer better protection than previous treatment concentrates. This study also examines
whether or not joint damage could be diagnosed earlier using ultrasound images. The primary
research question is whether EHL rIX with an intended trough level of >10% will improve the
outcome of joint health of elbow, ankle, and knee joints as assessed with ultrasound
assessments in patients with severe Hemophilia B.

Depending on their current treatment regimen, subjects will be in one of three groups: 1) on
demand, 2) prophylaxis with an intended trough of 1-5%, and 3) prophylaxis with an intended
trough of >10%. Subjects will have four annual study visits over three years: baseline, year
1, year 2, and year 3. At each of these visits, subjects will complete questionnaires, joint
assessments, have their blood taken, and have ultrasound images of their joints. The first 10
subjects will also have x-rays and MRIs of their joints for ultrasound validation.

Subjects are encouraged to come in during a painful episode for an examination, assessment,
and ultrasound of their joints and to come in again within 1-2 weeks after the painful
episode for a repeat examination, assessments, and ultrasound.

This study will be conducted at the Washington Center for Bleeding Disorders (WCBD) at
Bloodworks Northwest, Oregon Health & Science University (OHSU), University of California San
Diego (UCSD), University of California Los Angeles (UCLA), and Tulane University (TU).
Cumulatively across the five sites, up to 50 participants will be enrolled. Additional sites
may be added.

Inclusion Criteria:

- Severe hemophilia B (FIX <1%)

- Either on demand or on prophylaxis with rFIX or EHL-rIX products with the intention to
stay on the current regimen for the next 3 years

- For Group C, start of this treatment regimen up to 6 months prior is permissible

Exclusion Criteria:

- Other known bleeding disorder

- Other rheumatologic disorder affecting joints

- Other known neuromotor defect (making physical exam difficult)