Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A

Study Overview
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Brief Summary
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The investigators propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A. Per current standard of care, most patients are on prophylactic FVIII replacement therapy intravenously several times weekly with a goal of keeping the trough >1% FVIII. Recent phase 3 data suggest superior bleed protection with emicizumab prophylaxis every 1-2 weeks. It is the purpose of this study to longitudinally assess joint health and bone density over 3 years and to compare the effect of routine factor VIII prophylaxis with emicizumab prophylaxis.

Detailed Description
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Summary: This retrospective/prospective, non-randomized controlled study, whereby patients will be included in 1 of 2 groups depending on their current treatments as outlined below. Patients will be assigned to a specific group by the clinician/PI based on their current regimen with the intent to stay on this regimen for the next 3 years. Duration of Study and Subject Participation: Study subject enrollment is anticipated to occur over about 12 months and study duration per subject will be 3 years. Thus a total study duration of 4 years is anticipated. Intervention: By using musculoskeletal ultrasound, the investigators will measure joint health among participants and assess joint health changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by MSKUS at baseline and after 3 years. Other outcomes such as bone density, comparative assessment of joint and overall health status, and exploration of potential biomarkers for joint and bone health will also be assessed.

Official Title
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Effects of Emicizumab vs. Factor VIII Prophylaxis on Joint and Bone Health in Severe Hemophilia A

Conditions
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Hemophilia A

Intervention / Treatment
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* Other: assessment of joint health and bone density


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male gender Severe hemophilia A (factor VIII < 1%) Age ≥ 16 year Either on prophylaxis with factor VIII or emicizumab with the intention to stay on the current regimen for the next 3 years Willing and able to give written informed consent/assent Willing to undergo MSKUS, DEXA scan +/- collection of blood sampling for repository biomarkers Willing to come in for baseline and 3 yearly visits Willing to answer phone survey for bleeding and safety every 3 months Exclusion Criteria: Current FVIII inhibitor of > 0.6 BU Unable to take FVIII replacement 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 |
| --- | --- |
| Arm A<br>Male patients with severe Hemophilia A who use prophylaxis with IV factor VIII concentrate with intended trough >1%. | Other: assessment of joint health and bone density<br>* We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.<br>|
| Arm B<br>Male patients with severe Hemophilia A who use prophylaxis with SQ emicizumab. | Other: assessment of joint health and bone density<br>* We propose to study longitudinal joint and bone density changes in patients with severe Hemophilia A.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| joint health comparison | Joint health changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by MSKUS at baseline and after 3 years. | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| bone density comparison | Bone density changes over 3 years compared between group A (factor prophylaxis) vs. group B (emicizumab prophylaxis) as assessed by DEXA scan at baseline and after 3 years. | 3 years | 
| comparative assessment of joint and overall health | Observational comparative assessment of joint and overall health status evaluated by activity level, functional assessment, pain assessment, joint examination, and adherence. | 3 years | 
| mid-point assessment of joint health and bone density | Observational assessment of joint health and bone density at 1 and 2 years in the different groups. | 2 years | 
| biomarkers for joint and bone health | Exploration of potential biomarkers for joint and bone health. | through completion of study, average 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia A, Joint Health, Bone Density, Emicizumab, factor VIII prophylaxis