Joint Health Study

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Joint Health Study

Conditions
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Hemophilia B

Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Group A<br>Episodic treatment with FIX concentrates for bleeding episodes | |
| Group B<br>Prophylaxis using any FIX concentrate with an intended trough of 1-5% | |
| Group C<br>Prophylaxis with an extended half-life (EHL) FIX with an intended trough of >10% | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint health status | Joint health status in all six major joints (elbows, knees, and ankles) in all three groups as assessed by ultrasound | Change from baseline at up to three years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Joint and overall health status | Observational assessment of joint and overall health status evaluated by activity level, functional assessment, pain assessment, joint examination, and adherence | Change from baseline at up to three years | 
| Joint health at year 1 | Observational assessment of joint health at year one in the different groups | Change from baseline at up to one year | 
| Joint health at year 2 | Observational assessment of joint health at year two in the different groups | Change from baseline at up to two years | 
| Acute events/bleeding | Observational assessment of ultrasound findings during acute events/bleeding with an opportunity to follow longitudinally to gain understanding of natural evolution of bleeding as shown by ultrasound | Change from baseline at up to three years | 
| Biomarkers | Exploration of potential biomarkers for joint health | Change from baseline at up to three years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia B, FIX, Factor IX, Factor 9