Back to resultsProphylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Antihemophilic factor, recombinant, manufactured protein-free
Antihemophilic factor, recombinant, manufactured protein-free
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility Criteria
Inclusion Criteria: The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as tested at screening The subject has a documented history of at least 150 exposure days to factor VIII concentrates (either plasma-derived or recombinant) The subject is within 7 to 65 years of age The subject has a Karnofsky performance score > (greater than) 60 The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4 count >= 400 cells/mm³ (CD4 count determined at screening, if necessary) The subject has been on a documented on-demand treatment regimen for at least 12 months immediately prior to enrollment The subject has a documented history (e.g. in medical charts or dispensing information, or signed investigator statement) of at least 8 joint hemorrhages in the 12 months immediately prior to enrollment The subject resides within the coverage area of the mobile compliance device; coverage area will be determined at screening The subject or the subject's legally authorized representative has provided written informed consent Exclusion Criteria: The subject has a known hypersensitivity to factor VIII concentrates or mouse or hamster proteins The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by Bethesda or Nijmegen assay) at any time prior to screening The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4 BU (by Nijmegen Assay) in the central laboratory The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices. The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's Disease) The subject has been treated during the last sixty (60) days prior to or is being treated at screening/enrollment with an immunomodulating drug. The subject has participated in another investigational study within thirty (30) days of enrollment The subject has previously participated in a clinical study with rAHF-PFM The subject's clinical condition may require a major surgery (defined as moderate to critical risk and perioperative blood loss ≥ 500 mL) during the period of the subject's participation in the study The subject is female of childbearing potential with a positive pregnancy test
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
1
2
Arm Description
Standard prophylaxis
PK-driven prophylaxis
Outcomes
Primary Outcome Measures
Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens
Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Study Part 2): 1. Standard prophylaxis (20-40 IU/kg (every 48 ±6 hour), exact regimen determined by investigator) 2. PK-driven prophylaxis (20-80 IU/kg (every 72 ±6 hour), exact regimen determined by sponsor) Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X = bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the t-test.
Median Annualized Bleed Rate Estimates From Each of the 1 Year Prophylaxis Regimens
Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.
Secondary Outcome Measures
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens
Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Standard Prophylaxis Treatment TABR). Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and PK-Driven Prophylaxis Treatment Regimens
Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (PK-Driven Prophylaxis Treatment TABR) Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Any Prophylaxis Treatment Regimens
Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Any Prophylaxis Treatment TABR). Any Prophylaxis = Standard or PK-Driven Prophylaxis Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).
Total Weight-Adjusted Dose of rAHF-PFM Used Per Year for Each Prophylaxis Arm
Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.
Bleeding Episodes Treated With 1 to ≥4 Infusions
The number of bleeding episodes treated with 1, 2, 3, or ≥4 infusions of rAHF-PFM to achieve adequate hemostasis
Assessment of Hemostasis for Treatment of Bleeding Episodes
Number of rAHF-PFM-treated bleeding episodes with an assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief & bleeding cessation within ~8 hrs of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within ~8 hrs after infusion. Possibly requires >1 infusion for complete resolution; Fair: Probable or slight relief of pain & slight improvement in bleeding within ~8 hrs after infusion. Requires >1 infusion for complete resolution; None: No improvement or condition worsens
Total Area Under the Curve (AUC)
Total AUC estimated by AUC 0-48h plus an area extrapolated from the log-linear regression model
Area Under the Curve
Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
Maximum Plasma Concentration (C-max)
Maximal Factor VIII Concentration After Infusion
Adjusted Incremental Recovery (IR)
Change in factor VIII concentration from pre- to post-infusion at initial and termination study visits. Adjusted IR defined as: [Cmax (IU/dL) - pre-infusion FVIII (IU/dL)]/dose (IU/kg)
Terminal Half-life
Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Weight-Adjusted Clearance
Computed as the weight-adjusted dose divided by total AUC
Mean Residence Time
Computed as total Area Under the Moment Curve (AUMC) divided by the total AUC
Volume of Distribution at Steady State
Computed as weight-adjusted clearance * mean residence time
Factor VIII Inhibitor Development
Number of treated participants who developed factor VIII inhibitors
Number of Participants With AEs Related to Investigational Product (IP)
Number of treated participants with AEs judged to be possibly or probably related to treatment with IP
Number of Participants Who Reported ≥1 AE Regardless of Relatedness to Investigational Product (IP)
Number of treated participants with 1 or more AE regardless of relatedness to IP
Number of Participants Who Reported ≥1 AE Regardless of Relatedness to IP by Treatment Regimen
Number of Participants With SAEs by Preferred MedDRA Term and Treatment Regimen
AEs With Onset ≤1 Hour Following the End of an Infusion, Regardless of Relatedness
Number of Participants With Severe SAEs and Severe Non-SAEs by Preferred MedDRA Term and Treatment Regimen
This outcome is focused only on SEVERE SAEs and SEVERE non-SAEs
Baseline Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS
Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Baseline SF-36v1 Scores, where data available. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS at the End of Treatment Regimens
Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Baseline SF-36v1 Scores, where data available. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
HRQoL Scores Change From On-Demand Treatment Regimen Period Through Prophylaxis Period
Differences in health domain scores = (End of on-demand treatment) - (End of prophylaxis regimen). A negative value for the median difference equates to a larger domain score for the prophylaxis regimen Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Bodily Pain HRQoL Scores Change From On-Demand Period Through Prophylaxis Period
Change = (End of on-demand treatment) - (End of prophylaxis regimen). A negative value for the median difference equates to a larger domain score for the prophylaxis regimen. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores.
Physical Component Scores (PCS) HRQoL Scores Change From On-Demand Period Through Prophylaxis Period
Change = (End of on-demand treatment) - (End of prophylaxis regimen) A negative value for the median difference equates to a larger domain score for the prophylaxis regimen. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores.
Full Information
NCT ID
NCT00243386
First Posted
October 21, 2005
Last Updated
April 28, 2021
Sponsor
Baxalta now part of Shire
1. Study Identification
Unique Protocol Identification Number
NCT00243386
Brief Title
Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
Official Title
Advate Antihemophilic Factor (Recombinant), Plasma/Albumin Free Method (ADVATE rAHF-PFM): A Phase 4 Study Comparing Two Prophylactic Regimens in Subjects With Severe or Moderately Severe Hemophilia A
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
January 4, 2006 (Actual)
Primary Completion Date
June 16, 2010 (Actual)
Study Completion Date
June 16, 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Baxalta now part of Shire
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this randomized, two-arm parallel clinical study in 66 previously treated patients with severe or moderately severe hemophilia A is to compare the rate of bleeding episodes for standard prophylaxis (20-40 IU/kg every 48 ± 6 hours; actual dose determined by the investigator) with that of alternate prophylaxis (20-80 IU/kg every 72 + 6 hours; actual dose determined by Baxter utilizing an algorithm and the patient's pharmacokinetic data). The rates of bleeding episodes for the on-demand regimen and the prophylaxis regimens will also be compared for the cross-over portion of the study. Enrolled patients will be treated originally on demand for a period of 6 months and then they will be randomized into one of the prophylaxis arms. Prophylactic treatment will last for a period of 12 months +/- 2 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
82 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Active Comparator
Arm Description
Standard prophylaxis
Arm Title
2
Arm Type
Experimental
Arm Description
PK-driven prophylaxis
Intervention Type
Drug
Intervention Name(s)
Antihemophilic factor, recombinant, manufactured protein-free
Intervention Description
Standard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator
Intervention Type
Drug
Intervention Name(s)
Antihemophilic factor, recombinant, manufactured protein-free
Intervention Description
PK-driven prophylaxis: 20-80 IU/kg every 72+/-6 hours, actual dose determined by Baxter using an algorithm and the patient´s pharmacokinetic data
Primary Outcome Measure Information:
Title
Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens
Description
Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Study Part 2): 1. Standard prophylaxis (20-40 IU/kg (every 48 ±6 hour), exact regimen determined by investigator) 2. PK-driven prophylaxis (20-80 IU/kg (every 72 ±6 hour), exact regimen determined by sponsor) Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X = bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the t-test.
Time Frame
12 months ±2 weeks
Title
Median Annualized Bleed Rate Estimates From Each of the 1 Year Prophylaxis Regimens
Description
Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.
Time Frame
12 months ±2 weeks
Secondary Outcome Measure Information:
Title
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens
Description
Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Standard Prophylaxis Treatment TABR). Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).
Time Frame
On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)
Title
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and PK-Driven Prophylaxis Treatment Regimens
Description
Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (PK-Driven Prophylaxis Treatment TABR) Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).
Time Frame
On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)
Title
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Any Prophylaxis Treatment Regimens
Description
Annualized bleed rates were transformed using the square root of the number of bleeding episodes observed (X bleeds/year), X' = √(X + 0.5). This transformation was performed to stabilize the variance and align the sample distribution with the assumption of normality inherent in using the paired t-test. Mean Difference of Transformed Annualized Bleeding Rate (TABR) = (On-Demand Treatment TABR) - (Any Prophylaxis Treatment TABR). Any Prophylaxis = Standard or PK-Driven Prophylaxis Participants from the On-Demand portion of the study were subsequently randomized to either Standard Prophylaxis or PK-Driven Prophylaxis, (i.e the same participants were analyzed across the two measurement time periods).
Time Frame
On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)
Title
Total Weight-Adjusted Dose of rAHF-PFM Used Per Year for Each Prophylaxis Arm
Description
Participants were Randomized to Receive 1 of the 2 Following Prophylaxis Regimens (Part 2 of the study): 1. Standard prophylaxis- infusions every 48 ±6 hours, dosed at 20 to 40 IU/kg. 2. PK-driven prophylaxis- infusions every 72 ±6 hours dosed at 20 to 80 IU/kg.
Time Frame
12 months ±2 weeks
Title
Bleeding Episodes Treated With 1 to ≥4 Infusions
Description
The number of bleeding episodes treated with 1, 2, 3, or ≥4 infusions of rAHF-PFM to achieve adequate hemostasis
Time Frame
Throughout the study period (4 years and 5 months)
Title
Assessment of Hemostasis for Treatment of Bleeding Episodes
Description
Number of rAHF-PFM-treated bleeding episodes with an assessment of hemostasis (4-point ordinal scale): Excellent: Full pain relief & bleeding cessation within ~8 hrs of 1 infusion. Additional infusions may have been given to maintain hemostasis; Good: Definite pain relief and/or improvement in bleeding within ~8 hrs after infusion. Possibly requires >1 infusion for complete resolution; Fair: Probable or slight relief of pain & slight improvement in bleeding within ~8 hrs after infusion. Requires >1 infusion for complete resolution; None: No improvement or condition worsens
Time Frame
On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)
Title
Total Area Under the Curve (AUC)
Description
Total AUC estimated by AUC 0-48h plus an area extrapolated from the log-linear regression model
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Area Under the Curve
Description
Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Maximum Plasma Concentration (C-max)
Description
Maximal Factor VIII Concentration After Infusion
Time Frame
Within 1 hour post-infusion
Title
Adjusted Incremental Recovery (IR)
Description
Change in factor VIII concentration from pre- to post-infusion at initial and termination study visits. Adjusted IR defined as: [Cmax (IU/dL) - pre-infusion FVIII (IU/dL)]/dose (IU/kg)
Time Frame
30 minutes pre-infusion to 48 hours post-infusion
Title
Terminal Half-life
Description
Computed from the regression slope in the terminal phase of the model. Terminal half life is the time it takes for the plasma concentration or the amount of drug in the body to be reduced by 50%.
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Weight-Adjusted Clearance
Description
Computed as the weight-adjusted dose divided by total AUC
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Mean Residence Time
Description
Computed as total Area Under the Moment Curve (AUMC) divided by the total AUC
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Volume of Distribution at Steady State
Description
Computed as weight-adjusted clearance * mean residence time
Time Frame
Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Title
Factor VIII Inhibitor Development
Description
Number of treated participants who developed factor VIII inhibitors
Time Frame
Throughout study period (4 years and 5 months)
Title
Number of Participants With AEs Related to Investigational Product (IP)
Description
Number of treated participants with AEs judged to be possibly or probably related to treatment with IP
Time Frame
Throughout study period (4 years and 5 months)
Title
Number of Participants Who Reported ≥1 AE Regardless of Relatedness to Investigational Product (IP)
Description
Number of treated participants with 1 or more AE regardless of relatedness to IP
Time Frame
Throughout study period (4 years and 5 months)
Title
Number of Participants Who Reported ≥1 AE Regardless of Relatedness to IP by Treatment Regimen
Time Frame
Throughout the study period (4 years and 5 months)
Title
Number of Participants With SAEs by Preferred MedDRA Term and Treatment Regimen
Time Frame
Throughout the study period (4 years and 5 months)
Title
AEs With Onset ≤1 Hour Following the End of an Infusion, Regardless of Relatedness
Time Frame
Throughout study period (4 years and 5 months)
Title
Number of Participants With Severe SAEs and Severe Non-SAEs by Preferred MedDRA Term and Treatment Regimen
Description
This outcome is focused only on SEVERE SAEs and SEVERE non-SAEs
Time Frame
Throughout the study period (4 years and 5 months)
Title
Baseline Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS
Description
Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Baseline SF-36v1 Scores, where data available. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time Frame
Baseline
Title
Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS at the End of Treatment Regimens
Description
Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Baseline SF-36v1 Scores, where data available. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time Frame
End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Title
HRQoL Scores Change From On-Demand Treatment Regimen Period Through Prophylaxis Period
Description
Differences in health domain scores = (End of on-demand treatment) - (End of prophylaxis regimen). A negative value for the median difference equates to a larger domain score for the prophylaxis regimen Physical Functioning (PF); Role Limitation Due to Physical Health (RP); Bodily Pain (BP); General Health (GH); Vitality (VT); Social Functioning (SF); Role Limitation Due to Emotional Problems (RE); Mental Health (MH), Physical Component Score (PCS); Mental Component Score (MCS). Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores for each of the 8 HRQoL/SF-36 health domain scores.
Time Frame
End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Title
Bodily Pain HRQoL Scores Change From On-Demand Period Through Prophylaxis Period
Description
Change = (End of on-demand treatment) - (End of prophylaxis regimen). A negative value for the median difference equates to a larger domain score for the prophylaxis regimen. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores.
Time Frame
End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Title
Physical Component Scores (PCS) HRQoL Scores Change From On-Demand Period Through Prophylaxis Period
Description
Change = (End of on-demand treatment) - (End of prophylaxis regimen) A negative value for the median difference equates to a larger domain score for the prophylaxis regimen. Scores range 0-100, higher scores represent better health. There is no total overall score; scoring is done for subscores and summary scores. The raw data from the SF-36 items were transformed to norm based scores.
Time Frame
End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
7 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
The subject has severe or moderately severe hemophilia A as defined by a baseline factor VIII level <= 2% of normal, as tested at screening
The subject has a documented history of at least 150 exposure days to factor VIII concentrates (either plasma-derived or recombinant)
The subject is within 7 to 65 years of age
The subject has a Karnofsky performance score > (greater than) 60
The subject is human immunodeficiency virus negative (HIV-) or is HIV+ with a CD4 count >= 400 cells/mm³ (CD4 count determined at screening, if necessary)
The subject has been on a documented on-demand treatment regimen for at least 12 months immediately prior to enrollment
The subject has a documented history (e.g. in medical charts or dispensing information, or signed investigator statement) of at least 8 joint hemorrhages in the 12 months immediately prior to enrollment
The subject resides within the coverage area of the mobile compliance device; coverage area will be determined at screening
The subject or the subject's legally authorized representative has provided written informed consent
Exclusion Criteria:
The subject has a known hypersensitivity to factor VIII concentrates or mouse or hamster proteins
The subject has a history of factor VIII inhibitors with a titer >= 0.6 BU (by Bethesda or Nijmegen assay) at any time prior to screening
The subject has a detectable factor VIII inhibitor at screening, with a titer >= 0.4 BU (by Nijmegen Assay) in the central laboratory
The subject has severe chronic liver disease as evidenced by, but not limited to, any of the following: International Normalized Ratio (INR) > 1.4, hypoalbuminemia, portal vein hypertension including presence of otherwise unexplained splenomegaly and history of esophageal varices.
The subject has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (e.g., qualitative platelet defect or von Willebrand's Disease)
The subject has been treated during the last sixty (60) days prior to or is being treated at screening/enrollment with an immunomodulating drug.
The subject has participated in another investigational study within thirty (30) days of enrollment
The subject has previously participated in a clinical study with rAHF-PFM
The subject's clinical condition may require a major surgery (defined as moderate to critical risk and perioperative blood loss ≥ 500 mL) during the period of the subject's participation in the study
The subject is female of childbearing potential with a positive pregnancy test
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
City
Los Angeles
State/Province
California
Country
United States
City
Chicago
State/Province
Illinois
Country
United States
City
Indianapolis
State/Province
Indiana
Country
United States
City
Minneapolis
State/Province
Minnesota
Country
United States
City
New York
State/Province
New York
Country
United States
City
Oklahoma City
State/Province
Oklahoma
Country
United States
City
Portland
State/Province
Oregon
Country
United States
City
Hershey
State/Province
Pennsylvania
Country
United States
City
Seattle
State/Province
Washington
Country
United States
City
Vienna
Country
Austria
City
Brno
Country
Czechia
City
Prague
Country
Czechia
City
Athens
Country
Greece
City
Budapest
Country
Hungary
City
Debrecen
Country
Hungary
City
Pecs
Country
Hungary
City
Szeged
Country
Hungary
City
Szombathely
Country
Hungary
City
Florence
Country
Italy
City
Milano
Country
Italy
City
Gdansk
Country
Poland
City
Krakow
Country
Poland
City
Lublin
Country
Poland
City
Warsaw
Country
Poland
City
Wroclaw
Country
Poland
City
Moscow
Country
Russian Federation
City
Ljubljana
Country
Slovenia
City
Cardiff
Country
United Kingdom
City
Nottingham
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
22212248
Citation
Valentino LA, Mamonov V, Hellmann A, Quon DV, Chybicka A, Schroth P, Patrone L, Wong WY; Prophylaxis Study Group. A randomized comparison of two prophylaxis regimens and a paired comparison of on-demand and prophylaxis treatments in hemophilia A management. J Thromb Haemost. 2012 Mar;10(3):359-67. doi: 10.1111/j.1538-7836.2011.04611.x.
Results Reference
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Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
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