Once-A-Day Prophylaxis for Youth and Young Adults With Severe Hemophilia A

The primary objective of this study is to test the feasibility of a large-scale clinical trial of once-daily prophylaxis. The secondary objectives are to collect clinical efficacy outcomes so that we can better plan a large-scale study; we will estimate the effect size and variability of effect and resource utilization of once-daily prophylaxis to allow us to set a sample size for a definitive trial.

Hemophilia is an important and costly disorder; if left untreated, it may have serious consequences. The greatest impact of hemophilia occurs from recurrent bleeding into joints. The consequences of joint bleeding include pain associated with acute bleeding and later chronic arthropathy. Half of affected children with severe hemophilia have joint damage; joint damage is more frequent with increased bleeding. The prevention and treatment of bleeding is very expensive and therefore finding a cost-effective treatment is of high priority. Worldwide, two major treatment strategies have been used to prevent arthropathy - on demand therapy and factor prophylaxis. The goal of prophylaxis is to convert the severe to the moderate phenotype by providing circulating factor activity of greater than 1%. Patients with greater than 1% circulating factor VIII activity rarely have spontaneous hemarthroses. Therefore, the goal of providing circulating factor at this level is to eliminate spontaneous hemarthroses. The term primary prophylaxis suggests using preventative factor VIII replacement from a very early age. The term secondary prophylaxis is used to describe the application of prophylaxis at a later disease stage. In this study, secondary prophylaxis will be used. Once-daily prophylaxis is a novel application of hemophilia factor prophylaxis for youth and young adults. Before embarking on a costly definitive trial we feel that it is necessary to demonstrate that subjects will be willing to enroll and will be compliant with the therapy. Moreover, we need to establish an estimate of the effect of once-daily prophylaxis on bleeding rates, quality of life, and joint damage progression in order to design a definitive trial.

Low dose daily prophylaxis using FVIII products (e.g.Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS)

Starting at the 4-month visit, subjects will receive 250 units per day (if their weight is < 50 kg.) or 500 units per day (weight ≥ 50 kg.) of their usual preparation of factor VIII.

Tool developed to assess joint health in persons with hemophilia (PWH) through several assessments of 9 items in the 6 index joints (elbows, knees, and ankles). It has been internationally validated and has demonstrated inter-observer and test-retest reliability supporting its use as an effective physical examination assessment tool for PWH. Range: 0 - 124 ( Best score = 0, Worst score = 124)

Tool for assessment of 8 areas of musculoskeletal (MSK) function in patients with hemophlia. Range: 0 - 32 ( Best score = 0, Worst score = 32)

HRQoL Transformed Z-Score (Includes the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) and Haemo-QoL A)

Canadian Haemophilia Outcomes-Kids Life Assessment Tool is a validated 35-item disease specific measure of Quality of Life in boys with hemophilia ages 4 - 17 yrs. Range: 0 - 100 ( Best score = 100, Worst score = 0) The Adult Haemo-QoL Questionnaire is a validated disease specific measure of Quality of Life in adults with hemophilia ages > 18 yrs. It is a 41-item questionnaire that considers how hemophilia affects 4 specific areas of their life. These areas include day-to-day activities, moods & feelings, work or school life, family life & social life, and hemophilia treatment. Range: 0 - 100 ( Best score = 0, Worst score = 100) The two measures were transformed into a Z-score to enable comparison across both HRQoL scores. A score of 0 represents no difference between the means, whereas a positive z-score would indicate an improvement in HRQoL between baseline and end of study.

Treatment Satisfaction Questionnaire for Medication (TSQM) is an 11-item questionnaire used to evaluate patient satisfaction when starting a new medication and/or treatment. The areas of Effectiveness, Side-Effects, Convenience, and Global Satisfaction are assessed. A modified version (approved by developers) of the questionnaire with the deletion of side effects was used fro the purpose of the study. Effectiveness, Convenience, and Global Satisfaction all include the Range: 0 - 100 ( Best score = 0, Worst score = 100)

The Previous Day Physical Activity Recall is a well-validated assessment of habitual physical activity. Activity was reported on 1 weekend day, and 2 weekdays.The intensity of the activity was recorded in Metabolic Equivalents (METs) and categorized as Light (< 3.0 METs), Moderate (3.0 - 5.9 METs), Hard (6.0 - 8.9 METs), Very Hard (10.0 METs) Range: 0 - 10 METs per activity ( Best score = 10, Worst score = 0) MPA = Moderate Physical Activity VPA = Vigorous Physical Activity

The total number of index joint (elbows, knees, ankles) were extracted from the participant's (self-reported) diaries.

The mean yearly factor consumption of FVIII product on low dose daily prophylaxis was collected for comparison against standard prophylaxis (High dose alternate day treatment). Patient diaries indicating the amount of factor VIII product taken per daily infusion was collected on study.

Inclusion Criteria: Severe hemophilia A (<1% factor VIII) Age 12 to 24 years inclusive Male No current factor VIII inhibitor (an inhibitor will be defined as ≥ 0.6 Bethesda Units) within the past year Able to participate in a home infusion program with adequate peripheral venous access as assessed ny the treating investigator Exclusion Criteria: Important co-morbidities (Acquired Immunodeficiency Syndrome or symptomatic HIV infection, symptomatic hepatitis B or C infection) Other concomitant acquired or congenital bleeding disorder (e.g. von Willebrand's Disease) Receiving factor VIII replacement through central venous catheter