Weight-based Dosing in Hemophilia A
| Status: | Recruiting |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/23/2018 |
| Start Date: | September 2015 |
| End Date: | June 2019 |
| Contact: | Craig Seaman, MD, MS |
| Email: | seamanc@upmc.edu |
| Phone: | 412-209-7280 |
Weight-based Dosing in Hemophilia A: A Randomized, Controlled, Open-label, Crossover Trial to Measure Factor VIII Recovery Following Factor VIII Concentrate Dosing Based on Total Body Weight, Ideal Body Weight, and Lean Body Mass
Hemophilia A is an inherited (genetic) disease where a protein, factor VIII (FVIII), which
promotes blood clotting is missing or does not work properly. Individuals with hemophilia A
are at risk for bleeding. Bleeding is prevented and/or treated with recombinant factor VIII
(rFVIII), which is an FDA-approved treatment for Hemophilia A. Obesity is common among
patients with hemophilia. Some studies have shown that obese hemophilia patients may be able
to prevent bleeding with a lower dose of clotting factor than the dose they are currently
receiving. The lower dose is calculated based on what a patient should weigh rather than what
he does weigh. This is a clinical research study to test whether calculating rFVIII dosing
based on lean body mass and ideal body weight (what a person should weigh based on his
height) in overweight and obese patients with hemophilia is more accurate than calculating
rFVIII dosing based on what a person actually weighs.
promotes blood clotting is missing or does not work properly. Individuals with hemophilia A
are at risk for bleeding. Bleeding is prevented and/or treated with recombinant factor VIII
(rFVIII), which is an FDA-approved treatment for Hemophilia A. Obesity is common among
patients with hemophilia. Some studies have shown that obese hemophilia patients may be able
to prevent bleeding with a lower dose of clotting factor than the dose they are currently
receiving. The lower dose is calculated based on what a patient should weigh rather than what
he does weigh. This is a clinical research study to test whether calculating rFVIII dosing
based on lean body mass and ideal body weight (what a person should weigh based on his
height) in overweight and obese patients with hemophilia is more accurate than calculating
rFVIII dosing based on what a person actually weighs.
The investigators propose a single center, randomized, controlled, open-label, crossover
trial to determine if recombinant factor VIII (rFVIII) dosed according to lean body mass
(LBM) and ideal body weight (IBW) achieves a targeted FVIII recovery with better precision
than based on total body weight (TBW). The investigators hypothesize the use of LBM and IBW
to determine the dose of rFVIII necessary to attain a desired FVIII recovery of 2 +/- 0.2
IU/dl per IU/kg (100 +/- 10%) in overweight and obese (body mass index greater than or equal
to 25 mg/m2), adult males (age 18 or older) with hemophilia A (FVIII activity 40% or less)
will result in a 50% greater proportion of subjects within this range when compared to TBW.
Eligible patients receiving care at the Hemophilia Center of Western Pennsylvania (HCWP) will
be enrolled during clinic visits. Following enrollment and completion of screening
assessment, subjects will present to HCWP for three study visits with each study visit
occurring on successive weeks. Subjects will not have received any rFVIII for a period of at
least 72 hours prior to each study visit. Recombinant FVIII infusion based on TBW, LBM, or
IBW will take place during each study visit, and the order will be determined by
randomization. During each study visit, FVIII levels will be assessed by obtaining blood
samples before and at 10 and 30 minutes and 1 hour after infusion. Outcomes include the
proportion of subjects achieving a desired peak FVIII recovery value of 2 +/- 0.2 IU/dl per
IU/kg (100 +/- 10%) at 10 minutes following infusion of rFVIII dosed according to LBM and
TBW, IBW and TBW, and LBM and IBW. The investigators will use mixed effects logistic
regression to investigate the effect of using different weight-based dosing methods on
attaining target FVIII levels.
trial to determine if recombinant factor VIII (rFVIII) dosed according to lean body mass
(LBM) and ideal body weight (IBW) achieves a targeted FVIII recovery with better precision
than based on total body weight (TBW). The investigators hypothesize the use of LBM and IBW
to determine the dose of rFVIII necessary to attain a desired FVIII recovery of 2 +/- 0.2
IU/dl per IU/kg (100 +/- 10%) in overweight and obese (body mass index greater than or equal
to 25 mg/m2), adult males (age 18 or older) with hemophilia A (FVIII activity 40% or less)
will result in a 50% greater proportion of subjects within this range when compared to TBW.
Eligible patients receiving care at the Hemophilia Center of Western Pennsylvania (HCWP) will
be enrolled during clinic visits. Following enrollment and completion of screening
assessment, subjects will present to HCWP for three study visits with each study visit
occurring on successive weeks. Subjects will not have received any rFVIII for a period of at
least 72 hours prior to each study visit. Recombinant FVIII infusion based on TBW, LBM, or
IBW will take place during each study visit, and the order will be determined by
randomization. During each study visit, FVIII levels will be assessed by obtaining blood
samples before and at 10 and 30 minutes and 1 hour after infusion. Outcomes include the
proportion of subjects achieving a desired peak FVIII recovery value of 2 +/- 0.2 IU/dl per
IU/kg (100 +/- 10%) at 10 minutes following infusion of rFVIII dosed according to LBM and
TBW, IBW and TBW, and LBM and IBW. The investigators will use mixed effects logistic
regression to investigate the effect of using different weight-based dosing methods on
attaining target FVIII levels.
Inclusion Criteria:
1. Adult males age 18 or older.
2. Hemophilia A (FVIII activity 40% or less).
3. Overweight or obesity defined as a BMI of 25.0-29.9 and ≥ 30 mg/m2, respectively.
Exclusion Criteria:
1. Prior history of, or currently detectable, FVIII inhibitor defined as greater than or
equal to 0.6 Bethesda Units (BU); however, a subject with a past low-level
non-responding inhibitor defined as less than 5 BU, with no increase in titer
following FVIII exposure, and not detectable within 12 months of the study, despite
FVIII exposure during that period, will be allowed to enroll on study.
2. Allergy to FVIII products.
3. Current rFVIII requirements do not include at least a 72-hour period without rFVIII
administration.
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