POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies

Study Overview
=================
Brief Summary
-----------------
This is a prospective, randomized control trial in which each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy, which are both standard of care treatment for persons with Hemophilia A.

Detailed Description
-----------------
This is a research study to find out if there is a difference in the way children with hemophilia A form a clot and also evaluate if they develop tiny bleeds within the joint and subsequently early joint changes when receiving extended half-life factor VIII based replacement therapy vs non-FVIII based replacement as part of their hemophilia treatment to prevent spontaneous joint bleeds. Both therapies are standard of care therapies for patients with hemophilia A. The only experimental/research procedures as part of this study include the thrombin generation assay and ultrasound. All other procedures are standard of care.

Official Title
-----------------
POCUS: Hemostatic Potential and Joint Health in Patients With Severe Hemophilia A on Novel Replacement Therapies

Conditions
-----------------
Hemophilia A, Factor VIII

Intervention / Treatment
-----------------
* Drug: Eloctate
* Drug: Adynovate
* Drug: Emicizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects with moderate hemophilia A (baseline factor VIII activity 1-5%) or severe hemophilia A (baseline factor VIII activity <1%) on prophylactic standard half-life FVIII infusions OR subjects with moderate or severe hemophilia A who have not started prophylactic treatment Less than 18 years of age Exclusion Criteria: Subjects with documented FVIII inhibitor Subjects with a history of ≥ 2 target joints Subjects with a history of synovectomy Currently using medications known to impact bone and mineral metabolism (e.g., bisphosphonates, corticosteroids, estrogen, testosterone, calcitonin, thyroid hormone therapy); Disease states known to affect bone integrity (e.g., primary hyperparathyroidism, Paget's disease, clinically significant liver disease)

Ages Eligible for Study
-----------------
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Each patient will be randomly assigned to receive either extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Extended half-life factor VIII-based replacement therapy<br>Subjects who are either already on prophylactic standard half-life FVIII products or have not started prophylactic treatment will be randomized to start prophylactic extended half-life FVIII products or non-factor product (emicizumab). Both therapies are considered the current standard of care. The study has 4 planned visits at baseline, 1 month, 6 months, and 12 months. They will coincide with the standard of care visits. | Drug: Eloctate<br>* Eloctate is FDA-approved to treat patients with Hemophilia A. This drug will be used for extended half-life factor VIII-based replacement therapy.<br>* Other names: ELOCTATE- antihemophilic factor (recombinant), fc fusion protein;Drug: Adynovate<br>* Adynovate is FDA-approved to treat patients with Hemophilia A. This drug will be used for extended half-life factor VIII-based replacement therapy.<br>* Other names: ADYNOVATE- antihemophilic factor (recombinant) pegylated;|
| Active Comparator: Non-Factor VIII-based replacement therapy<br>Subjects who are either already on prophylactic standard half-life FVIII products or have not started prophylactic treatment will be randomized to start prophylactic extended half-life FVIII products or non-factor product (emicizumab). Both therapies are considered the current standard of care. The study has 4 planned visits at baseline, 1 month, 6 months, and 12 months. They will coincide with the standard of care visits. | Drug: Emicizumab<br>* Emicizumab is FDA-approved to treat patients with Hemophilia A. This drug will be used for non-factor VIII-based replacement therapy.<br>* Other names: HEMLIBRA- emicizumab injection, solution;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in hemostatic potential | Evaluate differences in hemostatic potential in persons with hemophilia A without evidence of hemophilic target joints who are receiving prophylactic FVIII-based replacement therapy versus non-FVIII replacement therapy by measuring thrombin generation potential via a plasma-based assay | Baseline, 1 month, 6 months, and 12 months from start of study | 
| Changes in early joint-health markers | Identify early joint-health markers associated with bleeding in persons with hemophilia A without evidence of hemophilic target joints who are receiving prophylactic FVIII-based replacement therapy versus non-FVIII replacement by measuring soft tissue and osteochondral changes among 6 joints (bilateral elbows, knees, and ankles) using point of care ultrasound between both treatment groups | Baseline, 1 month, 6 months, and 12 months from the start of study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in bleeding rates | Measure bleeding rates in persons with hemophilia A without evidence of hemophilic target joints on prophylactic FVIII-based replacement therapy versus non-FVIII replacement therapy by measuring the difference in annualized bleeding rates between the two treatment groups, as well as other surrogate markers of bleeding, or indirect causes of bleeding, which include FVIII inhibitor level, hemoglobin, and serum ferritin | Baseline and 12 months after start of study | 
| Changes in health-related quality of life and physical activity | Evaluate health-related quality of life and physical activity in persons with hemophilia A without evidence of hemophilic target joints on prophylactic FVIII-based replacement therapy versus non-FVIII replacement therapy using validated questionnaires | Baseline, 1 month, 6 months, and 12 months from the start of study | 
| Changes in joint health | Assess joint health in persons with hemophilia A without evidence of hemophilic target joints on prophylactic FVIII-based replacement therapy versus non-FVIII replacement therapy using validated outcome tool (Hemophilia Joint Health Score) | Baseline, 1 month, 6 months, and 12 months from the start of study |