Factor VIII (FVIII), Hemophilia A
Conditions
Brief summary
This is an observational research study to find out if there is a difference in the way children with moderate or severe hemophilia A, treated on two different types of factor replacement, 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.
Detailed description
This research study aims to compare the differences in the way children with moderate or severe hemophilia A respond when being treated with prophylactic extended half-life factor VIII based replacement therapy (such as Altuviiio) vs non-FVIII based replacement therapy (such as Hemlibra) as part of their hemophilia treatment to prevent spontaneous joint bleeds. This study will collect information about the patient's joint health, patient outcomes (using questionnaires), and laboratory testing at specific time points over 3 years. The study will use an overall approach of comparative effectiveness research (CER) methodology. We plan to recruit participants with severe (FVIII \<1%) and moderate (FVIII 1-4%) HA who take extended half-life factor VIII based replacement therapy or non-FVIII based replacement therapy as their clinically prescribed treatment. Both are standard of care treatment for persons with Hemophilia A (PwHA). Using CER principals, this study will analyze differences in 1) hemostatic potential and annualized bleeding rates (Aim 1-3) and 4) joint health (structural and functional) using the Hemophilia Joint Health Score (HJHS) and imaging markers to identify subclinical bleeding and early joint tissue changes in PwHA on novel FVIII and non-FVIII therapies already in use in practice (Aim 4). The proposed study will be the first systematic observational comparative effectiveness study in PwHA on two conventional, standard-of-care novel therapies with differing mechanisms of action to evaluate the overall effectiveness of treatment.
Interventions
DRUGHalf-life factor VIII based replacement therapy
Children with moderate or severe hemophilia A being treated with prophylactic extended half-life factor VIII based replacement therapy (such as Altuviiio) as part of their hemophilia treatment to prevent spontaneous joint bleeds.
DRUGNon-FVIII based replacement therapy
Children with moderate or severe hemophilia A being treated with non-FVIII based replacement therapy (such as Hemlibra) as part of their hemophilia treatment to prevent spontaneous joint bleeds.
Sponsors
University of Texas Southwestern Medical Center
Sanofi
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
6 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants with moderate or severe HA who are on prophylaxis with either weekly, biweekly, or every 4-weeks emicizumab or weekly efanesoctocog alfa for at least 2 months. * \>6 months of age
Exclusion criteria
* Participants with active FVIII inhibitor (\>0.5 BU/mL) * Presence of an additional bleeding disorder other than hemophilia A
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Thrombin Generation | Thrombin generation assay will be measured at 5 time points within a week of receiving dose of medication | To determine and compare in vivo thrombin generation parameters; endogenous thrombin potential (ETP) and peak thrombin (PT) for patients on efanesoctocog alfa or emicizumab |
| Hemophilia Joint Health Score | Obtained at baseline and every 6 months | To obtain and compare HJHS in patients on efanesoctocog alfa or emicizumab |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Annualized bleeding rate | From enrollment, every 6 months, until 3 years | To collect bleeding episodes in study participants and to calculate their respective total, treated, and joint annualized bleeding rates |
| Health related quality of life - CHO-KLAT | From enrollment, every 6 months, until 3 years | Canadian Hemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) will be used to evaluate the impact of different treatment strategies. CHO-KLAT will be obtained and compared in study participants on efanesoctocog alfa or emicizumab. |
| Health related quality of life - PedHAL | From enrollment, every 6 months, until 3 years | PedHAL is a validated patient-reported outcome measure designed to assess self-perceived functional abilities in children with hemophilia. PedHAL will be obtained and compared in study participants on efanesoctocog alfa or emicizumab |
| Health related quality of life - CATCH | From enrollment, every 6 months, until 3 years | CATCH (Comprehensive Assessment Tool of Challenges in Hemophilia) is a validated, multi-version patient-reported outcome instrument designed to assess the real-world impact of hemophilia on individuals and their caregivers. CATCH will be obtained and compared in study participants on efanesoctocog alfa or emicizumab |
| Joint Tissue Changes | From enrollment, every 6 months, until 3 years | Point-of-care ultrasound using JADE protocol to evaluate joint tissue changes will be obtained and compared in study participants on efanesoctocog alfa or emicizumab |
Countries
United States
Contacts
CONTACTJessica Garcia, MD
Outcome results
None listed