Pharmacokinetics and Safety of rFVIIIFc Manufactured at 15,000 L (15K) Scale (Elevate)
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ClinicalTrials.gov Identifier: NCT02502149 
Recruitment Status :
Completed
First Posted : July 20, 2015
Results First Posted : April 6, 2018
Last Update Posted : December 19, 2020

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Condition or disease  Intervention/treatment  Phase 

Severe Hemophilia A  Biological: rFVIIIFc  Phase 3 
Study Type :  Interventional (Clinical Trial) 
Actual Enrollment :  24 participants 
Allocation:  Randomized 
Intervention Model:  Parallel Assignment 
Masking:  None (Open Label) 
Primary Purpose:  Other 
Official Title:  A Randomized, OpenLabel Study to Evaluate the Pharmacokinetics and Safety of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) Manufactured at 15K Scale and at Different Vial Strengths in Previously Treated Subjects With Severe Hemophilia A 
Study Start Date :  August 2015 
Actual Primary Completion Date :  April 2017 
Actual Study Completion Date :  June 2017 
Arm  Intervention/treatment 

Experimental: rFVIIIFc (15K scale) 1000 IU vial
Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc (15K scale) 1000 IU vial at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 1000 IU vial.

Biological: rFVIIIFc
As per arm description
Other Names:

Experimental: rFVIIIFc (15K scale) 6000 IU vial
Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc high strength vial (15K scale) at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 6000 IU vial.

Biological: rFVIIIFc
As per arm description
Other Names:

 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by Onestage Activated Partial Thromboplastin Time (aPTT) Clotting Assay for Pharmacokinetic Assessment 1 (PK1) and Pharmacokinetic Assessment 2 (PK2) [ Time Frame: Predose and post dose at: 0.5 hour (hr), 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Incremental Recovery (IR) as Measured by Onestage aPTT Clotting Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg). Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Maximum Activity (Cmax) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Halflife (t½) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Halflife is time required for the concentration of the drug to reach half of its original value. Results were summarized overall for 15K 1000 IU/vial and 6000 IU/Vial (PK2).
 Clearance (CL) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]). Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Mean Residence Time (MRT) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Incremental Recovery (IR) as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in IU/dL per unit dose administered in IU/kg (IU/dL per IU/kg). Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Maximum Activity (Cmax) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Halflife (t½) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Clearance (CL) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]). Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Mean Residence Time (MRT) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hour (hr), 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity.
 Incremental Recovery (IR) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg).
 Maximum Activity (Cmax) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc.
 Halflife (t½) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value.
 Clearance (CL) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]).
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Mean Residence Time (MRT) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hour (hr), 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity.
 Incremental Recovery (IR) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg).
 Maximum Activity (Cmax) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc.
 Halflife (t½) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value.
 Clearance (CL) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]).
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Mean Residence Time (MRT) of rFVIIIFc as Measured by Onestage aPTT Clotting Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Incremental Recovery (IR) as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in IU/dL per unit dose administered in IU/kg (IU/dL per IU/kg). Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Maximum Activity (Cmax) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Halflife (t½) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Clearance (CL) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]). Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Mean Residence Time (MRT) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK1 and PK2 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/vial and 6000 IU/Vial (PK2).
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Incremental Recovery (IR) as Measured by the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in IU/dL per unit dose administered in IU/kg (IU/dL per IU/kg). Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Maximum Activity (Cmax) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Halflife (t½) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Clearance (CL) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]). Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Mean Residence Time (MRT) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 and PK3 [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time. Results were summarized overall for 15K rFVIIIFc 1000 IU/Vial and 6000 IU/Vial for PK2 and PK3.
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hour (hr), 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity.
 Incremental Recovery (IR) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg).
 Maximum Activity (Cmax) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc.
 Halflife (t½) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value.
 Clearance (CL) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]).
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Mean Residence Time (MRT) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK2 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Area Under the Concentrationtime Curve From Time Zero to Infinity (AUCinf) as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hour (hr), 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]AUCinf is area under the concentrationtime curve from time zero to infinity.
 Incremental Recovery (IR) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Incremental Recovery is defined as the increase in the circulating FVIII activity in international unit per deciliter (IU/dL) per unit dose administered in international unit per kilogram (IU/kg) (IU/dL per IU/kg).
 Maximum Activity (Cmax) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Cmax is defined as maximum activity of rFVIIIFc.
 Halflife (t½) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Time required for the concentration of the drug to reach half of its original value.
 Clearance (CL) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body.The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by the plasma Area Under the Plasma ConcentrationTime Curve From Time Zero to Infinite Time (AUC[0infinity]).
 Volume of Distribution at Steady State (Vss) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]Vss is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steadystate which is estimated by (D/AUC[0infinity])*(AUMC[0infinity])/AUC[0infinity]) where D is the dose of study drug, AUMC(0infinity) is the area under the first moment curve extrapolated to infinity and AUC(0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Mean Residence Time (MRT) of rFVIIIFc as Measured by the Twostage Chromogenic Assay for PK3 at Different Vial Strengths (1000 and 6000 IU/Vial) [ Time Frame: Predose and post dose at: 0.5 hr, 1 hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr ]The Mean Residence Time (MRT) is the average time at which the number of absorbed molecules reside in the body, after singledose administration, and calculated as area under the first moment curve AUMC (0infinity)/Area Under the Plasma ConcentrationTime Curve AUC (0infinity), where AUMC (0infinity) is area under the plasma concentrationtime first moment curve from time zero to infinite time and AUC (0infinity) is the area under the plasma concentrationtime curve from time zero to infinite time.
 Development of Inhibitors as Measured by the Nijmegenmodified Bethesda Assay [ Time Frame: At screening and predose on Day 1, 13 and 26 weeks after PK2 injection or at Early Termination (Approximately 43 weeks) ]An inhibitor test result greater than or equal to (>=)0.6 Bethesda units [BU]/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. The test was performed by the central laboratory using the Nijmegenmodified Bethesda Assay. An exact 95% confidence interval (CI) for the percentage of participants with a confirmed inhibitor was calculated using the ClopperPearson method for a binomial proportion. Percentage of participants with confirmed inhibitor development was summarized overall.
 Number of Participants With Treatment Emergent Adverse Events (TEAEs) at 15K Manufacturing Scale [ Time Frame: Approximately 43 weeks ]An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. Number of Participants with TEAEs were summarized overall.
 Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs) at 15K Manufacturing Scale [ Time Frame: Approximately 43 weeks ]An SAE is any untoward medical occurrence that at any dose: results in death or in the view of the Investigator, places the participant at immediate risk of death (a lifethreatening event); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; or results in a congenital anomaly/birth defect. All major surgeries will be reported as SAEs. An SAE may also be any other medically important event that, in the opinion of the Investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the SAE definition. Number of participants with TESAEs were summarized overall.
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Ages Eligible for Study:  12 Years and older (Child, Adult, Older Adult) 
Sexes Eligible for Study:  Male 
Accepts Healthy Volunteers:  No 
Key Inclusion Criteria:
 Have severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII as determined by onestage clotting assay from the central laboratory at Screening.
 Previously treated subject, defined as having at least 150 documented prior exposure days (EDs) to any recombinant and/or plasmaderived FVIII and/or cryoprecipitate products at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days.
 No history of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude the subject.
 No measurable inhibitor activity using the Nijmegenmodified Bethesda assay (>=0.6 Bethesda Unit per milliliter [BU/mL] is considered positive) at Screening.
Key Exclusion Criteria:
 Current enrollment in any interventional clinical study in which an investigational drug or approved therapy for investigational use is administered within 30 days prior to the Baseline Visit OR prior participation in any of the following Biogen studies: 998HA101 (NCT01027377), 997HA301 (NCT01181128), 8HA02PED (NCT01458106), 997HA307 (NCT02083965), and 8HA01EXT (NCT01454739).
 Previous participation in this study.
 Any concurrent clinically significant major disease that, in the opinion of the Investigator or Biogen, makes the subject unsuitable for participation in the study.
 Other coagulation disorder(s) in addition to hemophilia A.
 History of hypersensitivity or anaphylaxis associated with FVIII or intravenous (IV) immunoglobulin administration.
NOTE: Other protocoldefined inclusion/exclusion criteria may apply.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02502149
United States, California  
Research Site  
Los Angeles, California, United States, 90007  
United States, Illinois  
Research Site  
Chicago, Illinois, United States, 60612  
United States, Indiana  
Research Site  
Indianapolis, Indiana, United States, 46260  
United States, Kentucky  
Research Site  
Louisville, Kentucky, United States, 40202  
United States, Michigan  
Research Site  
East Lansing, Michigan, United States, 48823  
United States, Missouri  
Research Site  
Saint Louis, Missouri, United States, 63104  
United States, Utah  
Research Site  
Salt Lake City, Utah, United States, 84108  
United States, Washington  
Research Site  
Seattle, Washington, United States, 98104  
Australia, New South Wales  
Research Site  
Camperdown, New South Wales, Australia, 2050  
Australia, Victoria  
Research Site  
Melbourne, Victoria, Australia, 3004  
Australia, Western Australia  
Research Site  
Murdoch, Western Australia, Australia, 6150  
New Zealand  
Research Site  
Grafton, Auckland, New Zealand, 1023  
Research Site  
Newtown, Wellington, New Zealand, 6021  
Research Site  
Christchurch, New Zealand, 8011  
Research Site  
Hamilton, New Zealand, 3200 
Study Director:  Medical Director  Bioverativ Therapeutics Inc. 
Documents provided by Sanofi ( Bioverativ Therapeutics Inc. ):
Responsible Party:  Bioverativ Therapeutics Inc. 
ClinicalTrials.gov Identifier:  NCT02502149 
Other Study ID Numbers: 
997HA309 201400389521 ( EudraCT Number ) 
First Posted:  July 20, 2015 Key Record Dates 
Results First Posted:  April 6, 2018 
Last Update Posted:  December 19, 2020 
Last Verified:  March 2018 
rFVIIIFc Eloctate Hemophilia 
Hemophilia A Blood Coagulation Disorders, Inherited Blood Coagulation Disorders Hematologic Diseases Coagulation Protein Disorders 
Hemorrhagic Disorders Genetic Diseases, Inborn Factor VIII Coagulants 