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Weight-based Dosing in Hemophilia A

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ClinicalTrials.gov Identifier: NCT02586012
Recruitment Status : Recruiting
First Posted : October 26, 2015
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
Craig Seaman, University of Pittsburgh

Tracking Information
First Submitted Date  ICMJE October 22, 2015
First Posted Date  ICMJE October 26, 2015
Last Update Posted Date April 19, 2019
Actual Study Start Date  ICMJE September 2015
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
Proportion of subjects dosed based on LBM (Lean Body Mass) and TBW (Total Body Weight) achieving desired peak FVIII recovery. [ Time Frame: 3 weeks ]
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 expressed as IU/dL per IU/kg.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02586012 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 23, 2015)
  • Proportion of subjects dosed based on IBW (Ideal Body Weight) and TBW (Total Body Weight) achieving desired peak FVIII recovery. [ Time Frame: 3 weeks ]
    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 expressed as IU/dL per IU/kg.
  • Proportion of subjects dosed based on LBM (Lean Body Mass) and IBW (Ideal Body Weight) achieving desired peak FVIII recovery. [ Time Frame: 3 weeks ]
    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 expressed as IU/dL per IU/kg.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Weight-based Dosing in Hemophilia A
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia
Intervention  ICMJE Drug: rFVIII
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)].
Other Name: eloctate, advate, helixate, kogenate, recombinante
Study Arms  ICMJE
  • Experimental: TBW, LBM, IBW
    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).
    Intervention: Drug: rFVIII
  • Experimental: LBM, IBW, TBW
    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).
    Intervention: Drug: rFVIII
  • Experimental: IBW, TBW, LBM
    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).
    Intervention: Drug: rFVIII
  • Experimental: TBW, IBW, LBM
    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).
    Intervention: Drug: rFVIII
  • Experimental: LBM, TBW, IBW
    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).
    Intervention: Drug: rFVIII
  • Experimental: IBW, LBM, TBW
    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).
    Intervention: Drug: rFVIII
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 23, 2015)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Craig Seaman, MD, MS 412-209-7280 seamanc@upmc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02586012
Other Study ID Numbers  ICMJE PRO15010061
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Craig Seaman, University of Pittsburgh
Study Sponsor  ICMJE Craig Seaman
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Craig Seaman, MD, MS University of Pittsburgh
PRS Account University of Pittsburgh
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP