Weight-based Dosing in Hemophilia A

NCT02586012 | Terminated Phase 2 Results DMC

• 1 other identifier: PRO15010061
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemophilia

Outcome Measures

Primary Outcomes (1)

• Proportion of Subjects Dosed Based on LBM (Lean Body Mass) and TBW (Total Body Weight) Achieving Desired Peak FVIII Recovery.

  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.

  3 weeks

Secondary Outcomes (2)

• Proportion of Subjects Dosed Based on IBW (Ideal Body Weight) and TBW (Total Body Weight) Achieving Desired Peak FVIII Recovery.

  3 weeks

• Proportion of Subjects Dosed Based on LBM (Lean Body Mass) and IBW (Ideal Body Weight) Achieving Desired Peak FVIII Recovery.

  3 weeks

Study Arms (6)

TBW, LBM, IBW

EXPERIMENTAL

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).

Drug: rFVIII

LBM, IBW, TBW

EXPERIMENTAL

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).

Drug: rFVIII

IBW, TBW, LBM

EXPERIMENTAL

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).

Drug: rFVIII

TBW, IBW, LBM

EXPERIMENTAL

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).

Drug: rFVIII

LBM, TBW, IBW

EXPERIMENTAL

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).

Drug: rFVIII

IBW, LBM, TBW

EXPERIMENTAL

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).

Drug: rFVIII

Interventions

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

Also known as: eloctate, advate, helixate, kogenate, recombinant

IBW, LBM, TBW; IBW, TBW, LBM; LBM, IBW, TBW; LBM, TBW, IBW; TBW, IBW, LBM; TBW, LBM, IBW

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult males age 18 or older.
• Hemophilia A (FVIII activity 40% or less).
• Overweight or obesity defined as a BMI of 25.0-29.9 and ≥ 30 mg/m2, respectively.

You may not qualify if:

• 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.
• Allergy to FVIII products.
• Current rFVIII requirements do not include at least a 72-hour period without rFVIII administration.

Sponsors & Collaborators

• Craig Seaman: lead

Study Sites (1)

Hemophilia Center of Western Pennsylvania

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

Factor VIII; factor VIII-Fc fusion protein; F8 protein, human

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

Limitations and Caveats

Early termination due to poor enrollment prior to 24 subjects successfully completing the study. The rFVIII dose was erroneously calculated in 7 subjects resulting in the administration of a smaller than intended amount.

Results Point of Contact

• Title: Craig Seaman, MD
• Organization: University of Pittsburgh

seamanc@upmc.edu

412-209-7308

Study Officials

• Craig Seaman, MD, MS

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: October 26, 2015
• Study Start: September 1, 2015
• Primary Completion: January 10, 2020
• Study Completion: January 10, 2020
• Last Updated: September 25, 2020
• Results First Posted: September 25, 2020

Record last verified: 2020-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)