Factor Product Utilization and Health Outcomes in Patients With Hemophilia

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A, Congenital; Hemophilia B, Congenital

• Study Type: Observational
• Enrollment (Actual): 61

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2G2
      • BC Hemophilia Adult Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

• Sampling Method: Probability Sample

Study Population

This study will be conducted in male patients ≥12 years of age with severe and moderate hemophilia A or hemophilia B (baseline factor level <5%) who are able to sign the informed consent or assent.

Description

Inclusion Criteria:

1. Males ≥12 years of age with severe and moderate congenital hemophilia A or B (baseline factor activity<5%)
2. 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:

1. Unable or unwilling to provide informed consent
2. Patients with an existing bleeding disorder other than hemophilia A or B
3. History of hypersensitivity or severe allergic reactions to factor products
4. Patients currently participating in a phase 1-3 study with another factor replacement product
5. 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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
Hemophilia A patients on rFVIIIFc; Patients with hemophilia A who switch from on-demand or prophylactic treatment with rFVIII to rFVIIIFc
Hemophilia A patients on rFVIII; Patients with hemophilia A who remain on on-demand or prophylactic treatment with rFVIII
Hemophilia B patients on rFIXFc; Patients with hemophilia B who switch from on-demand or prophylactic treatment with rFIX to rFIXFc
Hemophilia A patients on rFIX; Patients with hemophilia B who remain on on-demand or prophylactic treatment with rFIX

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Biogen
• Investigators: Principal Investigator: Shannon Jackson, MD, Division of Hematology, Department of Medicine, University of British Columbia; Study Chair: Robert Klaassen, MD, Division of Hematology/Oncology, Department of Pediatrics, University of Ottawa; Study Chair: Man-Chiu Poon, MD, Division of Hematology, Department of Medicine, University of Calgary; Study Chair: Sue Robinson, MD, Division of Hematology, Department of Medicine, Dalhousie University; Study Chair: John Wu, MD, BC Children's hospital, Division of Hematology, Department of Medicine, University of British Columbia; Study Chair: Alfonso Iorio, MD, Hemophilia Program, Hamilton Health Services Program, McMaster University; Study Chair: Michelle Sholzberg, MD, Hemophilia Program, St. Michael's Hospital, University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): April 26, 2021
• Study Completion (Actual): April 26, 2021

Study Registration Dates

• First Submitted: May 26, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimate): June 10, 2016

Study Record Updates

• Last Update Posted (Actual): April 28, 2021
• Last Update Submitted That Met QC Criteria: April 26, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Hemophilia; Patient-reported outcomes; Recombinant factor VIII; Recombinant factor VIII Fc; Recombinant factor IX; Recombinant factor IX Fc
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Blood Coagulation Disorders; Hemophilia A; Hemophilia B
• Other Study ID Numbers: CAN-FAB-15-10911

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No