Hemophilia APhase 4NCT00243386
Prophylaxis Study of Recombinant Factor VIII Manufactured Protein-Free (rAHF-PFM) in Patients With Hemophilia A
A Phase 4 study testing Antihemophilic factor, recombinant, manufactured protein-free in people with Hemophilia A, run by Baxalta now part of Shire at 29 sites in 10 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 to 65 years
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Antihemophilic factor, recombinant, manufactured protein-free
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 82 participants
- Where
- 29 sitesin 10 countries
- Study dates
- 4 Jan 2006to 16 Jun 2010
- Phase
- Phase 4
- 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 7 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
29 sites in 10 countries.
29 sites in 10 countries
United States9 sites
Study site
Chicago, Illinois
Study site
Hershey, Pennsylvania
Study site
Indianapolis, Indiana
Study site
Los Angeles, California
Study site
Minneapolis, Minnesota
Study site
New York, New York
Study site
Oklahoma City, Oklahoma
Study site
Portland, Oregon
Study site
Seattle, Washington
Hungary5 sites
Study site
Budapest
Study site
Debrecen
Study site
Pécs
Study site
Szeged
Study site
Szombathely
Poland5 sites
Study site
Gdansk
Study site
Krakow
Study site
Lublin
Study site
Warsaw
Study site
Wroclaw
About this study
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
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.
- Conditions
- Hemophilia A
- Being tested
- Antihemophilic factor, recombinant, manufactured protein-free
- Medical subject headings
- Hemophilia A
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Antihemophilic factor, recombinant, manufactured protein-freeDrug
Standard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator
Antihemophilic factor, recombinant, manufactured protein-freeDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Standard prophylaxis Receives: Drug: Antihemophilic factor, recombinant, manufactured protein-free |
| 2 | Experimental | PK-driven prophylaxis Receives: Drug: Antihemophilic factor, recombinant, manufactured protein-free |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months ±2 weeks
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.
Measured: 12 months ±2 weeks
Secondary outcomes (26)
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).
Measured: On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)
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).
Measured: On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)
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).
Measured: On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)
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.
Measured: 12 months ±2 weeks
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
Measured: Throughout the study period (4 years and 5 months)
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
Measured: On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)
Total Area Under the Curve (AUC)
Total AUC estimated by AUC 0-48h plus an area extrapolated from the log-linear regression model
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
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
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Maximum Plasma Concentration (C-max)
Maximal Factor VIII Concentration After Infusion
Measured: Within 1 hour post-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)
Measured: 30 minutes pre-infusion to 48 hours post-infusion
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%.
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Weight-Adjusted Clearance
Computed as the weight-adjusted dose divided by total AUC
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Mean Residence Time
Computed as total Area Under the Moment Curve (AUMC) divided by the total AUC
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Volume of Distribution at Steady State
Computed as weight-adjusted clearance * mean residence time
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Factor VIII Inhibitor Development
Number of treated participants who developed factor VIII inhibitors
Measured: Throughout study period (4 years and 5 months)
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
Measured: Throughout study period (4 years and 5 months)
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
Measured: Throughout study period (4 years and 5 months)
Number of Participants Who Reported ≥1 AE Regardless of Relatedness to IP by Treatment Regimen
Measured: Throughout the study period (4 years and 5 months)
Number of Participants With SAEs by Preferred MedDRA Term and Treatment Regimen
Measured: Throughout the study period (4 years and 5 months)
AEs With Onset ≤1 Hour Following the End of an Infusion, Regardless of Relatedness
Measured: Throughout study period (4 years and 5 months)
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
Measured: Throughout the study period (4 years and 5 months)
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.
Measured: Baseline
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.
Measured: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
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.
Measured: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
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.
Measured: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
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.
Measured: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2005 (estimated)
- Study start4 Jan 2006
- Primary completion16 Jun 2010
- Study completion16 Jun 2010
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hemophilia AStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baxalta now part of Shire
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00243386
- Sponsor's protocol ID
- 060201
- Status last verified
- Apr 2021
- First submitted
- 21 Oct 2005
- Last updated
- 19 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 22212248
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00243386
- Acronym / sponsor ID
- 060201
- Conditions
- Hemophilia A
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 4 Jan 2006 (actual)
- Primary completion
- 16 Jun 2010 (actual)
- Study completion
- 16 Jun 2010 (actual)
- First posted
- 24 Oct 2005 (estimated)
- Results
- Posted 20 Nov 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: Antihemophilic factor, recombinant, manufactured protein-freeStandard prophylaxis |
| 2 | Experimental | Drug: Antihemophilic factor, recombinant, manufactured protein-freePK-driven prophylaxis |
Who may qualify
- Ages
- 7 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (10 listed)
- 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)
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 |
|---|---|---|
| Antihemophilic factor, recombinant, manufactured protein-freeStandard prophylaxis: 20-40 IU/kg every 48+/-6 hours, actual dose determined by investigator | Drug | 1 |
| Antihemophilic factor, recombinant, manufactured protein-freePK-driven prophylaxis: 20-80 IU/kg every 72+/-6 hours, actual dose determined by Baxter using an algorithm and the patient´s pharmacokinetic data | Drug | 2 |
Primary outcome
Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens
Time frame: 12 months ±2 weeks
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
Time frame: 12 months ±2 weeks
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.
26 secondary outcomes
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Standard Prophylaxis Treatment Regimens
Time frame: On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and PK-Driven Prophylaxis Treatment Regimens
Time frame: On-demand 6 months (± 2 weeks); followed by Prophylaxis 12 months (± 2 weeks)
Mean Difference of Transformed Annualized Bleeding Rate Between On-Demand and Any Prophylaxis Treatment Regimens
Time frame: On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)
Total Weight-Adjusted Dose of rAHF-PFM Used Per Year for Each Prophylaxis Arm
Time frame: 12 months ±2 weeks
Bleeding Episodes Treated With 1 to ≥4 Infusions
Time frame: Throughout the study period (4 years and 5 months)
Assessment of Hemostasis for Treatment of Bleeding Episodes
Time frame: On-demand 6 months (± 2 weeks); Prophylaxis 12 months (± 2 weeks)
Total Area Under the Curve (AUC)
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Area Under the Curve
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Maximum Plasma Concentration (C-max)
Time frame: Within 1 hour post-infusion
Adjusted Incremental Recovery (IR)
Time frame: 30 minutes pre-infusion to 48 hours post-infusion
Terminal Half-life
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Weight-Adjusted Clearance
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Mean Residence Time
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Volume of Distribution at Steady State
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Factor VIII Inhibitor Development
Time frame: Throughout study period (4 years and 5 months)
Number of Participants With AEs Related to Investigational Product (IP)
Time frame: Throughout study period (4 years and 5 months)
Number of Participants Who Reported ≥1 AE Regardless of Relatedness to Investigational Product (IP)
Time frame: Throughout study period (4 years and 5 months)
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)
Number of Participants With SAEs by Preferred MedDRA Term and Treatment Regimen
Time frame: Throughout the study period (4 years and 5 months)
AEs With Onset ≤1 Hour Following the End of an Infusion, Regardless of Relatedness
Time frame: Throughout study period (4 years and 5 months)
Number of Participants With Severe SAEs and Severe Non-SAEs by Preferred MedDRA Term and Treatment Regimen
Time frame: Throughout the study period (4 years and 5 months)
Baseline Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS
Time frame: Baseline
Health-related Quality of Life (HRQoL) Scores: PF, RP, BP, GH, VT, SF, RE, MH, PCS, and MCS at the End of Treatment Regimens
Time frame: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
HRQoL Scores Change From On-Demand Treatment Regimen Period Through Prophylaxis Period
Time frame: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Bodily Pain HRQoL Scores Change From On-Demand Period Through Prophylaxis Period
Time frame: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Physical Component Scores (PCS) HRQoL Scores Change From On-Demand Period Through Prophylaxis Period
Time frame: End of on-demand treatment period (6 months) and at study termination (approximately 18 months)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 22212248Valentino 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.
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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.
Study Director study director
Takeda
29 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Antihemophilic factor, recombinant, manufactured protein-free in people with Hemophilia A, run by Baxalta now part of Shire at 29 sites in 10 countries.
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 9 inclusion and 10 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 19 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States, Hungary, Poland, Czechia, Italy and 5 more countries. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 20 Nov 2012). 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?
Mean Transformed Annualized Bleed Rate Estimates From Each of the 1-year Prophylaxis Regimens (time frame: 12 months ±2 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00243386, which also lists 1 linked publication.
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 19 May 2021.