Expired Study
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Pittsburgh, Pennsylvania 15213


Purpose:

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.


Study summary:

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.


Criteria:

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.


Study is Available At:


Original ID:

PRO15010061


NCT ID:

NCT02586012


Secondary ID:


Study Acronym:


Brief Title:

Weight-based Dosing in Hemophilia A


Official Title:

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


Overall Status:

Terminated


Study Phase:

Phase 2


Genders:

Male


Minimum Age:

18 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

University of Pittsburgh


Oversight Authority:

United States: Data and Safety Monitoring Committee


Reasons Why Stopped:

Insufficient enrollment


Study Type:

Interventional


Study Design:


Number of Arms:

6


Number of Groups:

0


Total Enrollment:

31


Enrollment Type:

Actual


Overall Contact Information

Official Name:Craig Seaman, MD, MS
Principal Investigator
University of Pittsburgh

Study Dates

Start Date:September 2015
Completion Date:January 10, 2020
Completion Type:Actual
Primary Completion Date:January 10, 2020
Primary Completion Type:Actual
Verification Date:January 2020
Last Changed Date:January 15, 2020
First Received Date:October 22, 2015

Study Outcomes

Outcome Type:Primary Outcome
Measure:Proportion of subjects dosed based on LBM (Lean Body Mass) and TBW (Total Body Weight) achieving desired peak FVIII recovery.
Time Frame:3 weeks
Safety Issues:False
Description:Desired peak FVIII recovery value of 2 +/- 0.2 IU/dl per IU/kg (100 +/- 10%) at 10 minutes following infusion based on LBM and TBW. FVIII recovery values will be calculated as follows: [(weight in kg x observed FVIII recovery in IU/dL)/(dose in IU)] and e
Outcome Type:Secondary Outcome
Measure:Proportion of subjects dosed based on IBW (Ideal Body Weight) and TBW (Total Body Weight) achieving desired peak FVIII recovery.
Time Frame:3 weeks
Safety Issues:False
Description:Desired peak FVIII recovery value of 2 +/- 0.2 IU/dl per IU/kg (100 +/- 10%) at 10 minutes following infusion based on IBW and TBW. FVIII recovery values will be calculated as follows: [(weight in kg x observed FVIII recovery in IU/dL)/(dose in IU)] and e
Outcome Type:Secondary Outcome
Measure:Proportion of subjects dosed based on LBM (Lean Body Mass) and IBW (Ideal Body Weight) achieving desired peak FVIII recovery.
Time Frame:3 weeks
Safety Issues:False
Description:Desired peak FVIII recovery value of 2 +/- 0.2 IU/dl per IU/kg (100 +/- 10%) at 10 minutes following infusion based on LBM and IBW. FVIII recovery values will be calculated as follows: [(weight in kg x observed FVIII recovery in IU/dL)/(dose in IU)] and e

Study Interventions

Intervention Type:Drug
Name:rFVIII
Description:Recombinant FVIII concentrate is an FDA approved, and both efficacious and safe, therapy for the treatment and prevention of bleeding in hemophilia A. The rFVIII infusion dose will be calculated as follows: [(weight in kg x desired FVIII increase of 100 IU/dL)/(2)].
Arm Name:IBW, LBM, TBW
Other Name:eloctate, advate, helixate, kogenate, recombinante

Study Arms

Study Arm Type:Experimental
Arm Name:TBW, LBM, IBW
Description:Subjects will be randomized to receive rFVIII doses calculated by 3 separate methods over a 3 week period. Week 1, the dose will be based on TBW (Total Body Weight); Week 2, the dose will be based on LBM (Lean Body Mass); and Week 3, the dose will be based on IBW (Ideal Body Weight).
Study Arm Type:Experimental
Arm Name:LBM, IBW, TBW
Description:Subjects will be randomized to receive rFVIII doses calculated by 3 separate methods over a 3 week period. Week 1, the dose will be based on LBM (Lean Body Mass); Week 2, the dose will be based on IBW (Ideal Body Weight); and Week 3, the dose will be based on TBW (Total Body Weight).
Study Arm Type:Experimental
Arm Name:IBW, TBW, LBM
Description:Subjects will be randomized to receive rFVIII doses calculated by 3 separate methods over a 3 week period. Week 1, the dose will be based on IBW (Ideal Body Weight); Week 2, the dose will be based on TBW (Total Body Weight); and Week 3, the dose will be based on LBM (Lean Body Mass).
Study Arm Type:Experimental
Arm Name:TBW, IBW, LBM
Description:Subjects will be randomized to receive rFVIII doses calculated by 3 separate methods over a 3 week period. Week 1, the dose will be based on TBW (Total Body Weight); Week 2, the dose will be based on IBW (Ideal Body Weight); and Week 3, the dose will be based on LBM (Lean Body Mass).
Study Arm Type:Experimental
Arm Name:LBM, TBW, IBW
Description:Subjects will be randomized to receive rFVIII doses calculated by 3 separate methods over a 3 week period. Week 1, the dose will be based on LBM (Lean Body Mass); Week 2, the dose will be based on TBW (Total Body Weight); and Week 3, the dose will be based on IBW (Ideal Body Weight).
Study Arm Type:Experimental
Arm Name:IBW, LBM, TBW
Description:Subjects will be randomized to receive rFVIII doses calculated by 3 separate methods over a 3 week period. Week 1, the dose will be based on, IBW (Ideal Body Weight); Week 2, the dose will be based on LBM (Lean Body Mass); and Week 3, the dose will be based on TBW (Total Body Weight).

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Craig Seaman

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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