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

Phase 4
Recruiting
Conditions
Factor VIII
Hemophilia A
Interventions
Registration Number
NCT04690322
Lead Sponsor
University of Texas Southwestern Medical Center
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
28
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)

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Extended half-life factor VIII-based replacement therapyAdynovateSubjects 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.
Non-Factor VIII-based replacement therapyEmicizumabSubjects 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.
Extended half-life factor VIII-based replacement therapyEloctateSubjects 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.
Primary Outcome Measures
NameTimeMethod
Changes in early joint-health markersBaseline, 1 month, 6 months, and 12 months from the start of study

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

Changes in hemostatic potentialBaseline, 1 month, 6 months, and 12 months from start of study

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

Secondary Outcome Measures
NameTimeMethod
Changes in bleeding ratesBaseline and 12 months after start of study

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

Changes in health-related quality of life and physical activityBaseline, 1 month, 6 months, and 12 months from the start of study

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

Changes in joint healthBaseline, 1 month, 6 months, and 12 months from the start of study

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)

Trial Locations

Locations (1)

The University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

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