Hemophilia APhase 4NCT00289536
Dose-Response 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 8 sites in United States.
Trial summary
The purpose of this study is to determine the effect of 3 doses of ADVATE rAHF-PFM on initial recovery (% increase [IU/dL] per IU/kg infused) and major single-infusion pharmacokinetic parameters. The 3 doses are 15, 30, and 50 IU/kg. Read more about this study
- Who is it for?
- Ages 12 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
- 38 participants
- Where
- 8 sitesUnited States
- Study dates
- 2 Feb 2006to 1 Apr 2007
- 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 12 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The subject has severe hemophilia A as defined by a baseline factor VIII activity <1% of normal; tested at screening. (A minimum washout period of 3 days is required before the blood sample can be drawn to determine baseline factor VIII levels.)
- 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 12 to 65 years of age.
- The subject has a Karnofsky performance score >60.
- The subject is human immunodeficiency virus negative (HIV-) or HIV+ with CD4 count >=400 cells/mm3 (CD4 count determined at screening, if necessary).
- The subject or subject´s legally authorized representative has provided written informed consent.
Who cannot join
- The subject has a known hypersensitivity to mouse or hamster proteins or to factor VIII concentrates.
- The subject has a history of factor VIII inhibitors with titer >=0.8 BU (Bethesda Assay) or >=0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening.
- The subject has a detectable factor VIII inhibitor at screening, >=0.4 BU (Nijmegen modification of the Bethesda Assay), in the Baxter 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 participated in another investigational study within 30 days of enrollment.
- The subject´s clinical condition may require a major or moderate surgery (estimated blood loss >500 mL) during the period of participation in the study.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Study site
Cincinnati, Ohio
Study site
Houston, Texas
Study site
Iowa City, Iowa
Study site
Little Rock, Arkansas
Study site
Los Angeles, California
Study site
New Brunswick, New Jersey
Study site
Oklahoma City, Oklahoma
Study site
Peoria, Illinois
About this study
Official title: Advate Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method (ADVATE rAHF-PFM): A Phase 4 Study to Determine the Pharmacokinetic Response of Patients Diagnosed With Severe Hemophilia A to Different Doses of ADVATE rAHF-PFM
The purpose of this study is to determine the effect of 3 doses of ADVATE rAHF-PFM on initial recovery (% increase [IU/dL] per IU/kg infused) and major single-infusion pharmacokinetic parameters. The 3 doses are 15, 30, and 50 IU/kg. Prior to each infusion, subjects will not have received treatment with a factor VIII concentrate for at least 3 days. Blood samples will be drawn within 30 minutes pre-infusion and at 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32 and 48 hours post-infusion. A washout period of at least 3 days, but no more than 30 days between the last blood draw and the next infusion will be observed. During participation, subjects will maintain their preexisting treatment regimens with ADVATE rAHF-PFM or other factor VIII concentrate.
A secondary objective is to investigate the relationship between pharmacokinetic parameters at each dose level and the levels of von Willebrand factor ristocetin cofactor activity and von Willebrand factor antigen at baseline.
- 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-freeBiological
15 IU/kg rAHF-PFM
Antihemophilic factor, recombinant, manufactured protein-freeBiological
30 IU/kg rAHF-PFM
Antihemophilic factor, recombinant, manufactured protein-freeBiological
50 IU/kg rAHF-PFM
| Study group | Role | What they receive |
|---|---|---|
| Low Dose | Experimental | Not described Receives: Biological: Antihemophilic factor, recombinant, manufactured protein-free |
| Medium Dose | Experimental | Not described Receives: Biological: Antihemophilic factor, recombinant, manufactured protein-free |
| High Dose | Experimental | Not described Receives: Biological: Antihemophilic factor, recombinant, manufactured protein-free |
What is being measured
The primary outcome is the main question the study is designed to answer.
Initial Recovery
Percent increase in factor VIII concentration per dose from pre- to post-infusion
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion
Secondary outcomes (11)
Area Under the Curve/Dose
Area under the plasma factor VIII concentration versus time curve (AUC) estimated by linear trapezoidal method per dose.
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Terminal Half-life
Computed from the regression slope in the terminal phase of the model (the slope is biphasic). 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
Area Under the Curve
AUC estimated by linear trapezoidal method. The linear trapezoidal method is a numerical method used to approximate the area under a curve.
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Total Area Under the Curve
Total AUC with extrapolation using the slope of the β-phase
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Total Area Under the Moment Curve
Total area under the first moment curve (AUMC) estimated by linear trapezoidal methods
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Weight-adjusted Clearance
Computed as 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 AUMC divided by 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 CL * Mean Residence Time
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Maximum Plasma Concentration
Maximal factor VIII concentration after infusion
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Pre-infusion Von Willebrand Factor Ristocetin Cofactor Activity (VWF:Rco)
Percentage of normal VWF:Rco activity. Normal is a lab standard consisting of a non-hemophilic population. Relationships between baseline VWF:Rco and pharmacokinetic parameters (initial recovery, total AUC/dose, and half-life) were evaluated statistically.
Measured: At baseline and before each pharmacokinetic evaluation
Pre-infusion Von Willebrand Factor Antigen (VWF:Ag)
Percentage of VWF:Ag. Relationships between baseline VWF:Ag and pharmacokinetic parameters (initial recovery, total AUC/dose, and half-life) were evaluated statistically.
Measured: At baseline and before each pharmacokinetic evaluation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2006 (estimated)
- Study start2 Feb 2006
- Primary completion1 Apr 2007
- Study completion1 Apr 2007
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.
- 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 38 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
- NCT00289536
- Sponsor's protocol ID
- 060403
- Status last verified
- May 2021
- First submitted
- 9 Feb 2006
- Last updated
- 10 Jun 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 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 to Determine the Pharmacokinetic Response of Patients Diagnosed With Severe Hemophilia A to Different Doses of ADVATE rAHF-PFM
- ClinicalTrials.gov ID
- NCT00289536
- Acronym / sponsor ID
- 060403
- Conditions
- Hemophilia A
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 2 Feb 2006 (actual)
- Primary completion
- 1 Apr 2007 (actual)
- Study completion
- 1 Apr 2007 (actual)
- First posted
- 10 Feb 2006 (estimated)
- Results
- Posted 13 Jan 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effect of 3 doses of ADVATE rAHF-PFM on initial recovery (% increase [IU/dL] per IU/kg infused) and major single-infusion pharmacokinetic parameters. The 3 doses are 15, 30, and 50 IU/kg. Prior to each infusion, subjects will not have received treatment with a factor VIII concentrate for at least 3 days. Blood samples will be drawn within 30 minutes pre-infusion and at 0.25, 0.5, 1, 3, 6, 9, 24, 28, 32 and 48 hours post-infusion. A washout period of at least 3 days, but no more than 30 days between the last blood draw and the next infusion will be observed. During participation, subjects will maintain their preexisting treatment regimens with ADVATE rAHF-PFM or other factor VIII concentrate.
A secondary objective is to investigate the relationship between pharmacokinetic parameters at each dose level and the levels of von Willebrand factor ristocetin cofactor activity and von Willebrand factor antigen at baseline.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Low Dose | Experimental | Biological: Antihemophilic factor, recombinant, manufactured protein-free |
| Medium Dose | Experimental | Biological: Antihemophilic factor, recombinant, manufactured protein-free |
| High Dose | Experimental | Biological: Antihemophilic factor, recombinant, manufactured protein-free |
Who may qualify
- Ages
- 12 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- The subject has severe hemophilia A as defined by a baseline factor VIII activity <1% of normal; tested at screening. (A minimum washout period of 3 days is required before the blood sample can be drawn to determine baseline factor VIII levels.)
- 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 12 to 65 years of age.
- The subject has a Karnofsky performance score >60.
- The subject is human immunodeficiency virus negative (HIV-) or HIV+ with CD4 count >=400 cells/mm3 (CD4 count determined at screening, if necessary).
Key exclusion criteria (7 listed)
- The subject has a known hypersensitivity to mouse or hamster proteins or to factor VIII concentrates.
- The subject has a history of factor VIII inhibitors with titer >=0.8 BU (Bethesda Assay) or >=0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening.
- The subject has a detectable factor VIII inhibitor at screening, >=0.4 BU (Nijmegen modification of the Bethesda Assay), in the Baxter 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-free15 IU/kg rAHF-PFM | Biological | Low Dose |
| Antihemophilic factor, recombinant, manufactured protein-free30 IU/kg rAHF-PFM | Biological | Medium Dose |
| Antihemophilic factor, recombinant, manufactured protein-free50 IU/kg rAHF-PFM | Biological | High Dose |
Primary outcome
Initial Recovery
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion
Percent increase in factor VIII concentration per dose from pre- to post-infusion
11 secondary outcomes
Area Under the Curve/Dose
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Terminal Half-life
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
Total Area Under the Curve
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Total Area Under the Moment Curve
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
Maximum Plasma Concentration
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Pre-infusion Von Willebrand Factor Ristocetin Cofactor Activity (VWF:Rco)
Time frame: At baseline and before each pharmacokinetic evaluation
Pre-infusion Von Willebrand Factor Antigen (VWF:Ag)
Time frame: At baseline and before each pharmacokinetic evaluation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Hemophilia A
RecruitingObservational study
The CACHE Study: Coronary Artery Care in HaEmophilia
Haemophilia, Cardiovascular Diseases
Active, not recruitingObservational study
A Study to Learn About the Study Medicine -Hympavzi in Congenital Hemophilia Patients Without Inhibitors in Japan.
Hemophilia A or B
RecruitingPhase 1/2
A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of NXT007 in Persons With Severe or Moderate Hemophilia A
Hemophilia A
Active, not recruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Factor IX Gene Therapy With PF-06838435 in Adult Males With Moderately Severe to Severe Hemophilia B
Hemophilia B
Not yet recruiting
Safety of Intraosseous Anaesthesia in Children With Haemophilia
Haemophilia A, Haemophilia B
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
8 sites in 1 country: 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 8 sites in United States.
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 6 inclusion and 7 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 10 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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 13 Jan 2011). 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?
Initial Recovery (time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes post-infusion). 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 10 Jun 2021.