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

• ClinicalTrials.gov Identifier: NCT04690322
• Recruitment Status: Recruiting
• First Posted: December 30, 2020
• Last Update Posted: February 28, 2023
• Sponsor: University of Texas Southwestern Medical Center
• Information provided by (Responsible Party): Jessica Garcia, University of Texas Southwestern Medical Center

Tracking Information

• First Submitted Date: December 27, 2020
• First Posted Date: December 30, 2020
• Last Update Posted Date: February 28, 2023
• Actual Study Start Date: April 15, 2021
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 27, 2020)

• 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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 27, 2020)

• 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)

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Primary Purpose: Treatment

Condition

• Hemophilia A
• Factor VIII

Intervention

• 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.
  Other Name: ELOCTATE- antihemophilic factor (recombinant), fc fusion protein
• 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.
  Other Name: ADYNOVATE- antihemophilic factor (recombinant) pegylated
• Drug: Emicizumab
  Emicizumab is FDA-approved to treat patients with Hemophilia A. This drug will be used for non-factor VIII-based replacement therapy.
  Other Name: HEMLIBRA- emicizumab injection, solution

Study Arms

• 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.

  Interventions:

  • Drug: Eloctate
  • Drug: Adynovate
• 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.

  Intervention: Drug: Emicizumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: December 27, 2020): 28
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: July 2025
• Estimated Primary Completion Date: July 2025 (Final data collection date for primary outcome measure)

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Jessica Garcia, MD; 214-456-7000; Jessica.Garcia@utsouthwestern.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04690322
• Other Study ID Numbers: STU-2020-1378
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jessica Garcia, University of Texas Southwestern Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Texas Southwestern Medical Center
• Original Study Sponsor: Jessica Garcia
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jessica Garcia, MD; University of Texas Southwestern Medical Center

• PRS Account: University of Texas Southwestern Medical Center
• Verification Date: February 2023