Hemophilia APhase 1NCT00952822
Pharmacokinetic Study of ADVATE Reconstituted in 2 mL Sterile Water for Injection
A Phase 1 study testing Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII) in people with Hemophilia A, run by Baxalta now part of Shire at 11 sites in United States.
Trial summary
The purpose of this study is to determine the pharmacokinetics and safety of Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) reconstituted in 2 mL sterile water for injection (SWFI) and compare with those of rAHF-PFM reconstituted in 5 mL of SWFI. Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Hemophilia A
- What is being tested?
- Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 11 sitesUnited States
- Study dates
- 8 Aug 2008to 23 Oct 2009
- Phase
- Phase 1
- 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 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- The subject or subject's legally authorized representative has provided written informed consent
- The subject has severe hemophilia A as defined by a baseline FVIII activity <= 1% of normal; tested at screening
- The adolescent/adult subject has a documented history of at least 150 exposure days to FVIII concentrates (either plasma-derived or recombinant), and the pediatric subject has at least 50 exposure days
- The subject is >= 12 to <= 65 years of age for the complete pharmacokinetic assessment and >= 2 to < 12 years for the incremental recovery assessment The subject has a Karnofsky performance score > 60
- The subject is human immunodeficiency virus negative (HIV-) or HIV+ with stable CD4 count >= 200 cells/mm³ (CD4 count determined at screening, if necessary)
Who cannot join
- The subject has a known hypersensitivity to mouse or hamster proteins or to FVIII concentrates
- The subject has a history of FVIII inhibitors with titer >= 0. 5 BU (Bethesda Assay) or >= 0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening
- The subject has a detectable FVIII inhibitor at screening, >= 0.4 BU (Nijmegen modification of the Bethesda 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 Disease)
- The subject has received another investigational product within 30 days of enrollment
Show all 9Show fewer
- The subject's clinical condition may require major or moderate surgery (estimated blood loss > 500 mL) during the period of participation in the study
- Subjects with clinically significant medical, psychiatric, or cognitive illness, or recreational drug/alcohol use that, in the opinion of the investigator, would affect subject safety or compliance
- The subject is a female of childbearing potential with a positive pregnancy test at screening
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Study site
Atlanta, Georgia
Study site
Cincinnati, Ohio
Study site
Detroit, Michigan
Study site
Houston, Texas
Study site
Lexington, Kentucky
Study site
Louisville, Kentucky
Study site
New Brunswick, New Jersey
Study site
New York, New York
Study site
Philadelphia, Pennsylvania
Study site
Portland, Oregon
Study site
Washington D.C., District of Columbia
About this study
Official title: A Phase 1, Prospective, Randomized, Crossover Study to Compare the Pharmacokinetics and Safety of rAHF-PFM Reconstituted in 2 mL Versus 5 mL SWFI in Previously Treated Severe Hemophilia A Patients
The purpose of this study is to determine the pharmacokinetics and safety of Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) reconstituted in 2 mL sterile water for injection (SWFI) and compare with those of rAHF-PFM reconstituted in 5 mL of SWFI.
- Conditions
- Hemophilia A
- Being tested
- Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)
- 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-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)Biological
Also called ADVATE
Subjects are randomized to receive an infusion of rAHF-PFM reconstituted in 2 mL sterile water for infusion (SWFI) followed (after a wash-out period) by rAHF-PFM reconstituted in 5 mL SWFI or in 5 mL then 2 mL SWFI(cross-over design). Each subject will receive 2 infusions.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | ADVATE reconstituted in 2 mL sterile water for infusion Receives: Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII) |
| 2 | Active comparator | ADVATE reconstituted in 5 mL sterile water for infusion Receives: Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Secondary outcomes (9)
Total Area Under the Curve
Total AUC when the concentration is extrapolated to zero using the slope of the β-phase of the model
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Adjusted in Vivo Incremental Recovery
Increase in factor VIII concentration from pre- to post-infusion
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes 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 divided by the total AUC. 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
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
Maximum Plasma Concentration
Maximal factor VIII concentration post-infusion
Measured: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Number and Severity of Infusion Site Reactions
Infusion-related local reactions (including pain, tenderness, erythema, induration, and bruising) and severity were evaluated according to an FDA-defined grading scale (FDA Guidance for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials; 2007).
Measured: Within 5 minutes pre-infusion up to 24 hours post-infusion
Infusion Site Pain
Pain was assessed by participants (≥5 years of age) on a visual analog scale (VAS) from 0 (no pain) to 100 (worst possible pain).
Measured: Within 5 minutes post-infusion up to 24 hours post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2009 (estimated)
- Study start8 Aug 2008
- Primary completion23 Oct 2009
- Study completion23 Oct 2009
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 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 52 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
- NCT00952822
- Sponsor's protocol ID
- 060702
- Status last verified
- Apr 2021
- First submitted
- 4 Aug 2009
- Last updated
- 24 May 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 24 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Prospective, Randomized, Crossover Study to Compare the Pharmacokinetics and Safety of rAHF-PFM Reconstituted in 2 mL Versus 5 mL SWFI in Previously Treated Severe Hemophilia A Patients
- ClinicalTrials.gov ID
- NCT00952822
- Acronym / sponsor ID
- 060702
- Conditions
- Hemophilia A
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Baxalta now part of ShireIndustry (pharma, biotech, devices)
- Study start
- 8 Aug 2008 (actual)
- Primary completion
- 23 Oct 2009 (actual)
- Study completion
- 23 Oct 2009 (actual)
- First posted
- 6 Aug 2009 (estimated)
- Results
- Posted 21 Jul 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 pharmacokinetics and safety of Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM) reconstituted in 2 mL sterile water for injection (SWFI) and compare with those of rAHF-PFM reconstituted in 5 mL of SWFI.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)ADVATE reconstituted in 2 mL sterile water for infusion |
| 2 | Active comparator | Biological: Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)ADVATE reconstituted in 5 mL sterile water for infusion |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- The subject or subject's legally authorized representative has provided written informed consent
- The subject has severe hemophilia A as defined by a baseline FVIII activity <= 1% of normal; tested at screening
- The adolescent/adult subject has a documented history of at least 150 exposure days to FVIII concentrates (either plasma-derived or recombinant), and the pediatric subject has at least 50 exposure days
- The subject is >= 12 to <= 65 years of age for the complete pharmacokinetic assessment and >= 2 to < 12 years for the incremental recovery assessment The subject has a Karnofsky performance score > 60
- The subject is human immunodeficiency virus negative (HIV-) or HIV+ with stable CD4 count >= 200 cells/mm³ (CD4 count determined at screening, if necessary)
Key exclusion criteria (9 listed)
- The subject has a known hypersensitivity to mouse or hamster proteins or to FVIII concentrates
- The subject has a history of FVIII inhibitors with titer >= 0. 5 BU (Bethesda Assay) or >= 0.4 BU (Nijmegen modification of the Bethesda Assay) any time prior to screening
- The subject has a detectable FVIII inhibitor at screening, >= 0.4 BU (Nijmegen modification of the Bethesda 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 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-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII)Also: ADVATESubjects are randomized to receive an infusion of rAHF-PFM reconstituted in 2 mL sterile water for infusion (SWFI) followed (after a wash-out period) by rAHF-PFM reconstituted in 5 mL SWFI or in 5 mL then 2 mL SWFI(cross-over design). Each subject will receive 2 infusions. | Biological | 1, 2 |
Primary outcome
Area Under the Curve
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Area under the factor VIII (FVIII) plasma concentration versus time curve (AUC) from 0 to 48 hours estimated using the linear trapezoidal method
9 secondary outcomes
Total Area Under the Curve
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Adjusted in Vivo Incremental Recovery
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion to 30 minutes 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
Maximum Plasma Concentration
Time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours post-infusion
Number and Severity of Infusion Site Reactions
Time frame: Within 5 minutes pre-infusion up to 24 hours post-infusion
Infusion Site Pain
Time frame: Within 5 minutes post-infusion up to 24 hours post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2021.
- 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.
Study Director study director
Takeda
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Antihemophilic factor, recombinant, manufactured protein-free (rAHF-PFM). (Antihemophilic factor is also known as Factor VIII) in people with Hemophilia A, run by Baxalta now part of Shire at 11 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 5 inclusion and 9 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 24 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 11 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 21 Jul 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?
Area Under the Curve (time frame: Pharmacokinetic evaluations: 30 minutes pre-infusion up to 48 hours 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 24 May 2021.