Weight-based Dosing in Hemophilia A

NCT ID: NCT02586012

Last Updated: 2020-09-25

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2020-01-10

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. We aim to have 24 subjects successfully complete the study.

Conditions

Hemophilia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: EXPERIMENTAL

rFVIII

Intervention Type: DRUG

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

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).

Group Type: EXPERIMENTAL

rFVIII

Intervention Type: DRUG

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

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).

Group Type: EXPERIMENTAL

rFVIII

Intervention Type: DRUG

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

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).

Group Type: EXPERIMENTAL

rFVIII

Intervention Type: DRUG

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

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).

Group Type: EXPERIMENTAL

rFVIII

Intervention Type: DRUG

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

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).

Group Type: EXPERIMENTAL

rFVIII

Intervention Type: DRUG

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

Interventions

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: \[(weight in kg x desired FVIII increase of 100 IU/dL)/(2)\].

Intervention Type: DRUG

Other Intervention Names

eloctate, advate, helixate, kogenate, recombinant

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Craig Seaman

OTHER

Sponsor Role: lead

Responsible Party

Craig Seaman

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Craig Seaman, MD, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

PRO15010061

Identifier Type: -

Identifier Source: org_study_id