Hemophilia APhase 2NCT00717626
Once-A-Day Prophylaxis for Youth and Young Adults With Severe Hemophilia A
A Phase 2 study testing Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS in people with Hemophilia A, run by The Hospital for Sick Children at 3 sites in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 12 to 24 years, men only
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesCanada
- Study dates
- Jul 2008to Apr 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 24 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
Canada3 sites
Hospital Sainte-Justine
Montreal, Quebec
St. Michael's Hospital
Toronto, Ontario
The Hospital for Sick Children
Toronto, Ontario
About this study
Official title: Pilot Study of 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.
Read the 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.
- Conditions
- Hemophilia A
- Being tested
- Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS
- Keywords
- Hemophilia, Prophylaxis, Youth, Young Adults, Feasibility
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FSDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Daily administration of low dose FVIII | Experimental | Low dose daily prophylaxis using FVIII products (e.g.Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS) Receives: Drug: Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 4 months, 12 months
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)
Measured: 4 months, 12 months
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.
Measured: 4 months, 12 months
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)
Measured: 4 months, 12 months
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
Measured: 4 months and 12 months
Total Number of Index Joint Bleeds
The total number of index joint (elbows, knees, ankles) were extracted from the participant's (self-reported) diaries.
Measured: 4, 8, and 12 months
Secondary outcomes (1)
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Brian Feldman, The Hospital for Sick Children
- Investigators
- Brian Feldman, MD,MSc,FRCPC, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00717626
- Sponsor's protocol ID
- 1000012140
- Status last verified
- Sep 2020
- First submitted
- 14 Jul 2008
- Last updated
- 8 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Once-A-Day Prophylaxis for Youth and Young Adults With Severe Hemophilia A
- ClinicalTrials.gov ID
- NCT00717626
- Acronym / sponsor ID
- 1000012140
- Conditions
- Hemophilia A
- Keywords
- Hemophilia, Prophylaxis, Youth, Young Adults, Feasibility
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 17 Jul 2008 (estimated)
- Results
- Posted 8 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Daily administration of low dose FVIII | Experimental | Drug: Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FSLow dose daily prophylaxis using FVIII products (e.g.Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS) |
Who may qualify
- Ages
- 12 to 24 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FSStarting 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. | Drug | Daily administration of low dose FVIII |
Primary outcome
Hemophilia Joint Health Score (HJHS) 2.0
Time frame: 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)
Time frame: 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)
HRQoL Transformed Z-Score (Includes the Canadian Haemophilia Outcomes-Kids Life Assessment Tool (CHO-KLAT) and Haemo-QoL A)
Time frame: 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.
Treatment Satisfaction Questionnaire for Medication (TSQM) . Version II
Time frame: 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
Time frame: 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
Total Number of Index Joint Bleeds
Time frame: 4, 8, and 12 months
The total number of index joint (elbows, knees, ankles) were extracted from the participant's (self-reported) diaries.
1 secondary outcome
Mean Yearly Factor Consumption of FVIII Product on Low Dose Daily Prophylaxis
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Brian Feldman, MD,MSc,FRCPC principal investigator
The Hospital for Sick Children
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Kogenate FS, Advate, or Humate-P, Recombinate, Helixate FS in people with Hemophilia A, run by The Hospital for Sick Children at 3 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemophilia Joint Health Score (HJHS) 2.0 (time frame: 4 months, 12 months). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2020.