Hemophilia A
Conditions
Keywords
Hemophilia, Prophylaxis, Youth, Young Adults, Feasibility
Brief summary
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.
Detailed description
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.
Interventions
DRUGKogenate 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.
Sponsors
The Hospital for Sick Children
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 24 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HRQoL Transformed Z-Score (Includes the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) and Haemo-QoL A) | 4 months, 12 months | 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. |
| Hemophilia Joint Health Score (HJHS) 2.0 | 4 months, 12 months | 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) |
| Functional Independence Score in Hemophilia (FISH) | 4 months, 12 months | Tool for assessment of 8 areas of musculoskeletal (MSK) function in patients with hemophlia. Range: 0 - 32 ( Best score = 0, Worst score = 32) |
| Total Number of Index Joint Bleeds | 4, 8, and 12 months | The total number of index joint (elbows, knees, ankles) were extracted from the participant's (self-reported) diaries. |
| Treatment Satisfaction Questionnaire for Medication (TSQM) . Version II | 4 months, 12 months | 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 | 4 months and 12 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Yearly Factor Consumption of FVIII Product on Low Dose Daily Prophylaxis | 12 months | 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. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Daily Administration of Low Dose FVIII Low dose daily prophylaxis using FVIII products (e.g.Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS)
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. | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Daily Administration of Low Dose FVIII |
|---|---|
| Age, Categorical <=18 years | 4 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Region of Enrollment Canada | 14 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 0 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Functional Independence Score in Hemophilia (FISH)
Tool for assessment of 8 areas of musculoskeletal (MSK) function in patients with hemophlia. Range: 0 - 32 ( Best score = 0, Worst score = 32)
Time frame: 4 months, 12 months
Population: Mean of differences between start of intervention (4 months) and end of study (12 months)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Daily Administration of Low Dose FVIII | Functional Independence Score in Hemophilia (FISH) | 0.31 score on a scale |
Primary
Hemophilia Joint Health Score (HJHS) 2.0
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)
Time frame: 4 months, 12 months
Population: Mean of differences between start of intervention (4 months) and end of study (12 months)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Daily Administration of Low Dose FVIII | Hemophilia Joint Health Score (HJHS) 2.0 | 3.77 score on a scale |
Primary
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.
Time frame: 4 months, 12 months
Population: Mean of differences between start of intervention (4 months) and end of study (12 months)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Daily Administration of Low Dose FVIII | HRQoL Transformed Z-Score (Includes the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) and Haemo-QoL A) | 0 score on a scale |
Primary
The Previous Day Physical Activity Recall
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
Time frame: 4 months and 12 months
Population: Mean of differences between start of intervention (4 months) and end of study (12 months)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Daily Administration of Low Dose FVIII | The Previous Day Physical Activity Recall | Weekday 1 MPA | -0.15 score on a scale |
| Daily Administration of Low Dose FVIII | The Previous Day Physical Activity Recall | Weekday 1 VPA | -0.69 score on a scale |
| Daily Administration of Low Dose FVIII | The Previous Day Physical Activity Recall | Weekday 2 MPA | -0.15 score on a scale |
| Daily Administration of Low Dose FVIII | The Previous Day Physical Activity Recall | Weekday 2 VPA | 0 score on a scale |
| Daily Administration of Low Dose FVIII | The Previous Day Physical Activity Recall | Weekend MPA | -0.92 score on a scale |
| Daily Administration of Low Dose FVIII | The Previous Day Physical Activity Recall | Weekend VPA | 2.31 score on a scale |
Primary
Total Number of Index Joint Bleeds
The total number of index joint (elbows, knees, ankles) were extracted from the participant's (self-reported) diaries.
Time frame: 4, 8, and 12 months
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daily Administration of Low Dose FVIII | Total Number of Index Joint Bleeds | 4 months - Index joint bleeds | 0 Bleeds |
| Daily Administration of Low Dose FVIII | Total Number of Index Joint Bleeds | 8 months - Index joint bleeds | 0 Bleeds |
| Daily Administration of Low Dose FVIII | Total Number of Index Joint Bleeds | 12 months - Index joint bleeds | 0 Bleeds |
Primary
Treatment Satisfaction Questionnaire for Medication (TSQM) . Version II
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)
Time frame: 4 months, 12 months
Population: Mean of differences between start of intervention (4 months) and end of study (12 months)
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Daily Administration of Low Dose FVIII | Treatment Satisfaction Questionnaire for Medication (TSQM) . Version II | TSQM Effectiveness | -6.41 score on a scale |
| Daily Administration of Low Dose FVIII | Treatment Satisfaction Questionnaire for Medication (TSQM) . Version II | TSQM Convenience | -4.70 score on a scale |
| Daily Administration of Low Dose FVIII | Treatment Satisfaction Questionnaire for Medication (TSQM) . Version II | TSQM Global Satisfaction | -5.13 score on a scale |
Secondary
Mean Yearly Factor Consumption of FVIII Product on Low Dose Daily Prophylaxis
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.
Time frame: 12 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Daily Administration of Low Dose FVIII | Mean Yearly Factor Consumption of FVIII Product on Low Dose Daily Prophylaxis | 211528 International Units (IU) |