Comparison of Ideal vs. Actual Weight Base Factor Dosing

Study Overview
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Brief Summary
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This is a randomized, prospective, multicenter study to examine whether or not the current recommended factor dosing strategy - i.e., dosing by actual body weight - in overweight and obese patients with Hemophilia A may deliver excessive clotting factor to achieve the desired result of bleeding prevention and cessation. This study also examines ways to prevent delivering excessive factor by using a patient's ideal body weight as a new dosing strategy compared to the current dosing strategy. The hypothesis being tested is that factor dosing based on ideal body weight will result in protective factor levels.

Detailed Description
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This is a randomized, prospective, multicenter, open-label, crossover study to examine whether or not the current recommended factor dosing strategy, i.e., dosing by actual body weight in overweight and obese patients, may deliver more clotting factor than necessary to cause bleeding to stop in participants with Hemophilia A who use Factor VIII (FVIII). This study also examines ways to prevent delivering too much factor by using a participant's ideal body weight as a new dosing strategy compared to the current dosing strategy. The hypothesis being tested is that factor dosing based on ideal body weight will result in hemostatic factor levels. The study will be conducted at the Washington Center for Bleeding Disorders (WCBD) at Bloodworks Northwest, Oregon Health & Science University (OHSU), Seattle Children's Hospital (SCH), and Providence Sacred Heart Children's Hospital (SH). Cumulatively across the four sites, up to 20 participants will be enrolled. Randomization will be performed centrally at WCBD. Participants will provide their own factor. Prior to the first study-related dose, participants will stop taking any FVIII products for either 48 hours if currently using a short-acting FVIII product or 72 hours for a long acting FVIII product. Factor levels will be measured immediately before and at multiple points after two different factor doses. Subjects will be randomized to start their dosage based either on actual body weight or ideal body weight first and then crossover to receive dosage based on the other category.

Official Title
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Comparison of Ideal vs. Actual Weight Base Factor Dosing

Conditions
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Hemophilia A

Intervention / Treatment
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* Other: Ideal Body Weight First
* Other: Actual Body Weight First


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hemophilia A Able and willing to comply with pharmacokinetic testing schedule Either overweight or obese BMI using CDC definitions by age Exclusion Criteria: Inhibitor of > 0.6 BU twice in the past, or documented abnormal recovery of less than 66% (of expected) in the past Known other bleeding disorder Known other prolongation in aPTT (lupus anticoagulant, FXII deficiency) Female

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Health Services Research
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Subjects are randomized to receive factor based either on ideal body weight or actual body weight first followed by receiving factor based on the other category next
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ideal Body Weight First<br>Randomized to receive factor product based on ideal body weight first | Other: Ideal Body Weight First<br>* Randomized to receive 50 U/kg (+/- 20%) of the factor product participants routinely use based on ideal body weight. For participants age 12-19, ideal weight is calculated using the McLaren method. For participants age 20 and over, ideal weight is calculated using the following equation: [50kg + (2.3kg*every inch over 5 feet)].<br>|
| Experimental: Actual Body Weight First<br>Randomized to receive factor product based on actual body weight first | Other: Actual Body Weight First<br>* Randomized to receive 50 U/kg (+/- 20%) of the factor product participants routinely use based on actual body weight.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery | Compare the recovery with FVIII between doses calculated on actual body weight versus ideal body weight in subjects with Hemophilia A | Change from baseline at up to two months | 
| Underdosing | Determine the likelihood of underdosing when using ideal body weight | Change from baseline at up to two months | 
| Overdosing | Determine the likelihood of overdosing when using actual body weight | Change from baseline at up to two months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of half-life | Determine the effect on half-life of these dosing strategies | Change from baseline at up to two months | 
| Effect on hemophilia severity | Determine the effect of pharmacokinetic differences on hemophilia severity | Change from baseline at 20-40 minutes, 5-7 hours, 20-26 hours, and 44-50 hours for both half-life and extended half-life and also at 69-75 hours, and 93-99 hours for extended half-life | 
| Regular half-life vs. extended half-life Regular half-life vs. extended half-life | Determine differences in participants receiving regular half-life versus extended half-life products | Change from baseline at up to two months | 
| Overweight vs. obese | Determine the differences, if any, between overweight and obese participants | Change from baseline at up to two months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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FVIII, Hemophilia A, Ideal body weight, Actual body weight