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

Overview

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.

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 2023

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.

Interventions

  • Drug: Eloctate
    • Eloctate is FDA-approved to treat patients with Hemophilia A. This drug will be used for extended half-life factor VIII-based replacement therapy.
  • Drug: Adynovate
    • Adynovate is FDA-approved to treat patients with Hemophilia A. This drug will be used for extended half-life factor VIII-based replacement therapy.
  • Drug: Emicizumab
    • Emicizumab is FDA-approved to treat patients with Hemophilia A. This drug will be used for non-factor VIII-based replacement therapy.

Arms, Groups and Cohorts

  • Active Comparator: Extended half-life factor VIII-based replacement therapy
    • 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.
  • Active Comparator: Non-Factor VIII-based replacement therapy
    • 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.

Clinical Trial Outcome Measures

Primary Measures

  • Changes in hemostatic potential
    • Time Frame: Baseline, 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
  • Changes in early joint-health markers
    • Time Frame: Baseline, 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

Secondary Measures

  • Changes in bleeding rates
    • Time Frame: Baseline 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 activity
    • Time Frame: Baseline, 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 health
    • Time Frame: Baseline, 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)

Participating in This Clinical Trial

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)

Gender Eligibility: All

Minimum Age: N/A

Maximum Age: 17 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Jessica Garcia
  • Provider of Information About this Clinical Study
    • Sponsor-Investigator: Jessica Garcia, Assistant Professor – University of Texas Southwestern Medical Center
  • Overall Official(s)
    • Jessica Garcia, MD, Principal Investigator, University of Texas Southwestern Medical Center
  • Overall Contact(s)
    • Jessica Garcia, MD, 214-456-7000, Jessica.Garcia@utsouthwestern.edu

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