Factor Product Utilization and Health Outcomes in Patients With Hemophilia

Study Overview
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Brief Summary
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Recombinant factor VIII Fc (rFVIIIFc) and recombinant factor IX Fc (rFIXFc) are extended half-life coagulation factors approved by Health Canada in 2014 for the treatment of severe hemophilia A and B, respectively. The objectives of this observational study is to describe the change in annual factor consumption, clinical and patient-reported outcomes for patients who switch from recombinant factor VIII (rFVIII) and recombinant factor IX (rFIX) to rFVIIIFc/ rFIXFc in Canada, and to explore clinicians' and patients' reasons for switching or not switching.

Official Title
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Factor Product Utilization and Health Outcomes in Patients With Hemophilia A and B in Canada: An Observational Study of Real-world Outcomes

Conditions
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Hemophilia A, Congenital, Hemophilia B, Congenital

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males ≥12 years of age with severe and moderate congenital hemophilia A or B (baseline factor activity<5%) Ability to understand the purpose and risks of the study and provide signed and dated informed consent or assent and authorization to use protected health information (PHI) in accordance with national and local privacy regulations. Exclusion Criteria: Unable or unwilling to provide informed consent Patients with an existing bleeding disorder other than hemophilia A or B History of hypersensitivity or severe allergic reactions to factor products Patients currently participating in a phase 1-3 study with another factor replacement product Unable to adhere to the study requirements based on the judgment of the Prescribing Physician (e.g. unable to enter accurate and timely infusion and bleeding records)

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Hemophilia A patients on rFVIIIFc<br>Patients with hemophilia A who switch from on-demand or prophylactic treatment with rFVIII to rFVIIIFc | |
| Hemophilia A patients on rFVIII<br>Patients with hemophilia A who remain on on-demand or prophylactic treatment with rFVIII | |
| Hemophilia B patients on rFIXFc<br>Patients with hemophilia B who switch from on-demand or prophylactic treatment with rFIX to rFIXFc | |
| Hemophilia A patients on rFIX<br>Patients with hemophilia B who remain on on-demand or prophylactic treatment with rFIX | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the total annualized factor consumption (in units/kilogram/year) |  | From baseline to 24-month period on rFVIIIFc or rFIXFc | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in health-related quality of life (HRQoL) SF-36 | HRQoL will be measured using Short Form 36 (SF-36) in all patients | From baseline to 3 months, 12 months and 24 months | 
| Change in health-related quality of life (HRQoL) Haem-A-Qol | Haem-A-QoL in patients over age 18 years | From baseline to 3 months, 12 months and 24 months | 
| Change in health-related quality of life (HRQoL) CHO-KLAT | The Canadian Hemophilia Outcomes- Kids Life Assessment Tool (CHO-KLAT) in patients between ages 13-18 years | From baseline to 3 months, 12 months and 24 months | 
| Change in the Work Productivity and Impairment Questionnaire (WPAI+CIQ: HS) score |  | From baseline to 3 months, 12 months and 24 months | 
| Change in chronic pain Numeric Rating Scale (0-10) |  | From baseline to 3 months, 12 months and 24 months | 
| Change in chronic pain Bodily Pain subscale of SF-36 |  | From baseline to 3 months, 12 months and 24 months | 
| Change in physical activity (IPAQ) | Physical activity will be measured using the International Physical Activity Questionnaire (IPAQ) | From baseline to 3 months, 12 months and 24 months | 
| Change in physical activity Physical Functioning subscale of SF-36. |  | From baseline to 3 months, 12 months and 24 months | 
| Change in treatment satisfaction Treatment domain of Haem-A-QoL |  | From baseline to 3 months, 12 months and 24 months | 
| Change in treatment satisfaction abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) questionnaire. | Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) questionnaire. | From baseline to 3 months, 12 months and 24 months | 
| Change in mood Mental Health subscale of SF-36 | partner or caregiver's subjective assessment of subject's mood from baseline to 3 months. | From baseline to 3 months, 12 months and 24 months | 
| Change in mood partner/caregiver subjective assessment numeric rating scale (0-10) | Partner or caregiver's subjective assessment of subject's mood from baseline to 3 months. | From baseline to 3 months only | 
| Clinicians' and patients' reason for switching to rFVIIIFc | Choice among list of common reasons for changing product | Baseline through study completion, an average of 2 years | 
| Clinicians' and patients' reason for switching to rFIXFc | Choice among list of common reasons for changing product | Baseline through study completion, an average of 2 years | 
| Product used for treatment of breakthrough bleeding and surgical procedures | Choice among list of products | Baseline through study completion, an average of 2 years | 
| Total annualized number of factor infusions |  | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 
| Annualized bleeding rate |  | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 
| Ratio of annual factor consumption-to-annual factor prescription |  | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 
| Number of infusions required to treat a breakthrough bleed |  | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 
| Incremental factor utilization per joint bleed avoided | Difference in annualized factor utilization between Fc and regular non-Fc prophylaxis, divided by the difference in annualized joint bleeding rate between the two groups. | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 
| Adverse events leading to permanent discontinuation of rFVIIIFc or rFIXFc |  | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 
| Serious adverse events |  | From baseline to 24-month period after product switch (or 24-month period on study for non-switchers) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hemophilia, Recombinant factor VIII, Recombinant factor VIII Fc, Recombinant factor IX, Patient-reported outcomes, Recombinant factor IX Fc