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CompletedNCT02083965Updated Dec 19, 2020Results posted

Pharmacokinetics of rFVIIIFc at Two Vial Strengths

A Phase 1 interventional study of rFVIIIFc in Severe Hemophilia A, sponsored by Bioverativ Therapeutics Inc.. Completed at 8 sites in 3 countries. Open to male participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2020-12-19.

Sponsored by Bioverativ Therapeutics Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
19
Allocation
Randomized
Ages
12 Years and older
Sex
Male
01

Study summary

The primary objective of the study is to characterize the pharmacokinetics (PK) of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A. The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months for a continued treatment period.

Read the detailed description

This is a randomized, open-label, crossover study during which each participant receives a single injection of rFVIIIFc from 2 different vial concentrations (PK assessment). After the PK assessment, participants are provided with rFVIIIFc for either prophylactic or episodic (on-demand) treatment for up to 6 months.

02

Conditions studied

  • Severe Hemophilia A

Browse trials for

03

In context

Hemophilia A

866 studies on the registry are indexed under Hemophilia A; 137 are open to participants now.

This study's enrollment of 19 is below the median of 28 across 512 interventional studies indexed under Hemophilia A.

Browse Hemophilia A studies →

Lead sponsor

Bioverativ Therapeutics Inc. is the lead sponsor of 12 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
Male
Accepts healthy volunteers
No

Eligibility criteria

Key Inclusion Criteria:

  • Have severe hemophilia A
  • Previously treated subject, defined as having at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc- study drug or commercial product) 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 subjects.
  • No measurable inhibitor activity using the Nijmegen-modified Bethesda assay at Screening.
  • Platelet count ≥100,000 platelets/μL at screening
  • CD4 lymphocytes >200 mm3 if known as HIV antibody positive at screening.
  • Viral load of \<400 copies/mL if known HIV antibody positive at screening.

Key Exclusion Criteria:

  • Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion.
  • Previous treatment with rFVIIIFc as study drug or commercial product.
  • Other coagulation disorder(s) in addition to hemophilia A.
  • History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
  • Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other nonsteroidal anti-inflammatory drugs are permitted).
  • Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Day 1. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days at a dose of ≤1 mg/kg within 12 weeks prior to Day 1) and/or inhaled steroids.

NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply

05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • Experimental
    rFVIIIFc 1000 / 3000 PK Assessment

    A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.

    Biological: rFVIIIFc

  • Experimental
    rFVIIIFc 3000 / 1000 PK Assessment

    A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.

    Biological: rFVIIIFc

Interventions

  • BiologicalrFVIIIFc

    Administered as specified in the treatment arm.

    Also known as: Eloctate, antihemophilic factor [recombinant] FC fusion protein, recombinant coagulation factor VIII Fc fusion protein, efmoroctocog alfa, BIIB031, Elocta

06

What researchers measure

Primary outcomes

  1. Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay

    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  2. Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay

    The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

Secondary outcomes

  1. Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay

    Maximum measured concentration of rFVIIIFc.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  2. Half-life (t½) as Measured by aPTT Clotting Assay

    Time required for the concentration of the drug to reach half of its original value.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  3. Clearance (CL) as Measured by the aPTT Clotting Assay

    The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  4. Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay

    The apparent volume of distribution at steady state. (Volume of distribution 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.)

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  5. Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay

    The average time at which the number of absorbed molecules reside in the body, after single-dose administration.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  6. Time of Cmax (Tmax) as Measured by aPTT Clotting Assay

    Time at which maximum activity (Cmax) is observed.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  7. Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay

    Area under the plasma concentration time-curve from zero to the last measured concentration.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  8. Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay

    First order rate constant associated with the terminal portion of the curve (lambda z) .

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  9. Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay

    Percentage of AUCinf extrapolated from the last data point to infinity.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  10. Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay

    Dose normalized area under the FVIII activity-time curve.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  11. Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT

    The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  12. AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay

    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  13. IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay

    The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  14. Cmax as Measured by Two-Stage Chromogenic Clotting Assay

    Maximum measured concentration of rFVIIIFc.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  15. t½ as Measured by Two-Stage Chromogenic Clotting Assay

    Time required for the concentration of the drug to reach half of its original value.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  16. CL as Measured by Two-Stage Chromogenic Clotting Assay

    The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  17. Vss as Measured by Two-Stage Chromogenic Clotting Assay

    The apparent volume of distribution at steady state. (Volume of distribution 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.)

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  18. MRT as Measured by Two-Stage Chromogenic Clotting Assay

    The average time at which the number of absorbed molecules reside in the body, after single-dose administration.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  19. Tmax as Measured by Two-Stage Chromogenic Clotting Assay

    Time at which maximum activity (Cmax) is observed.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  20. AUClast as Measured by Two-Stage Chromogenic Clotting Assay

    Area under the plasma concentration time-curve from zero to the last measured concentration.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  21. Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay

    First order rate constant associated with the terminal portion of the curve (lambda z).

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  22. AUCext as Measured by Two-Stage Chromogenic Clotting Assay

    Percentage of AUCinf extrapolated from the last data point to infinity.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  23. DNAUC as Measured by Two-Stage Chromogenic Clotting Assay

    Dose normalized area under the FVIII activity-time curve.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  24. Vz as Measured by Two-Stage Chromogenic Clotting Assay

    The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

    Time frame: Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

  25. Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay

    An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. An exact 95% confidence interval (CI) for the proportion of subjects with a confirmed inhibitor was calculated using the Clopper-Pearson method for a binomial proportion. Percentage of participants with confirmed inhibitor development was summarized overall.

    Time frame: Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only)

07

Results

Posted Aug 19, 2016

Participant flow

PK Period 1
Participant flow — PK Period 1
MilestonerFVIIIFc 1000 / 3000rFVIIIFc 3000 / 1000
Started109
Completed109
Not completed00
Washout Period
Participant flow — Washout Period
MilestonerFVIIIFc 1000 / 3000rFVIIIFc 3000 / 1000
Started109
Completed109
Not completed00
PK Period 2
Participant flow — PK Period 2
MilestonerFVIIIFc 1000 / 3000rFVIIIFc 3000 / 1000
Started109
Completed109
Not completed00
Treatment Period
Participant flow — Treatment Period
MilestonerFVIIIFc 1000 / 3000rFVIIIFc 3000 / 1000
Started108
Completed98
Not completed10
Withdrew: Other10

Outcome measures

PrimaryArea Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay

Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU*h/dL
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay
IU*h/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay2888.9 (2440.0 to 3420.5)2646.3 (2149.8 to 3257.5)
PrimaryIncremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay

The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU/dL
Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay
IU/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay2.33 (2.182 to 2.487)2.412 (2.169 to 2.682)
SecondaryMaximum Activity (Cmax) as Measured by the aPTT Clotting Assay

Maximum measured concentration of rFVIIIFc.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU/dL
Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay
IU/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay122.2 (113.77 to 131.25)129.08 (114.62 to 145.37)
SecondaryHalf-life (t½) as Measured by aPTT Clotting Assay

Time required for the concentration of the drug to reach half of its original value.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · hours
Half-life (t½) as Measured by aPTT Clotting Assay
hoursrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Half-life (t½) as Measured by aPTT Clotting Assay18.28 (16.10 to 20.75)17.49 (15.22 to 20.10)
SecondaryClearance (CL) as Measured by the aPTT Clotting Assay

The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · mL/h/kg
Clearance (CL) as Measured by the aPTT Clotting Assay
mL/h/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Clearance (CL) as Measured by the aPTT Clotting Assay1.807 (1.534 to 2.128)2.016 (1.642 to 2.476)
SecondaryVolume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay

The apparent volume of distribution at steady state. (Volume of distribution 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.)

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · mL/kg
Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay
mL/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay47.00 (43.87 to 50.35)48.65 (44.83 to 52.79)
SecondaryMean Residence Time (MRT) as Measured by the aPTT Clotting Assay

The average time at which the number of absorbed molecules reside in the body, after single-dose administration.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · hours
Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay
hoursrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay26.01 (22.49 to 30.08)24.13 (20.46 to 28.46)
SecondaryTime of Cmax (Tmax) as Measured by aPTT Clotting Assay

Time at which maximum activity (Cmax) is observed.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · hours
Time of Cmax (Tmax) as Measured by aPTT Clotting Assay
hoursrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Time of Cmax (Tmax) as Measured by aPTT Clotting Assay0.66 (0.55 to 0.79)0.58 (0.51 to 0.67)
SecondaryArea Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay

Area under the plasma concentration time-curve from zero to the last measured concentration.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU*h/dL
Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay
IU*h/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Area Under the Curve to the Last Measurable Time Point (AUClast) as Measured by aPTT Clotting Assay2792.5 (2378.5 to 3278.6)2562.2 (2100.8 to 3125.0)
SecondaryTerminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay

First order rate constant associated with the terminal portion of the curve (lambda z) .

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · 1/h
Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay
1/hrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Terminal Exponential Rate Constant (Lambda Z) as Measured by aPTT Clotting Assay0.03792 (0.03340 to 0.04304)0.03963 (0.03449 to 0.04554)
SecondaryPercentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay

Percentage of AUCinf extrapolated from the last data point to infinity.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · percentage of AUCinf
Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay
percentage of AUCinfrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Percentage of AUCinf From the Last Data Point to Infinity (AUCext) as Measured by aPTT Clotting Assay2.561 (1.703 to 3.852)2.279 (1.505 to 3.45)
SecondaryDose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay

Dose normalized area under the FVIII activity-time curve.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU*h/dL per IU/kg
Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay
IU*h/dL per IU/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Dose Normalized Area Under the Curve (DNAUC) as Measured by aPTT Clotting Assay55.35 (47.00 to 65.18)49.6 (40.4 to 60.9)
SecondaryTerminal Exponential Volume of Distribution (Vz) as Measured by aPTT

The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · mL/kg
Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT
mL/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Terminal Exponential Volume of Distribution (Vz) as Measured by aPTT47.65 (43.73 to 51.93)50.87 (45.56 to 56.8)
SecondaryAUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay

Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU*h/dL
AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay
IU*h/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
AUCinf as Estimated From the FVIII Activity Data as Measured by Two-Stage Chromogenic Clotting Assay2649.0 (2230.2 to 3146.5)2628.0 (2206.2 to 3130.5)
SecondaryIR, K Value as Measured by Two-Stage Chromogenic Clotting Assay

The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU/dL per IU/kg
IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay
IU/dL per IU/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
IR, K Value as Measured by Two-Stage Chromogenic Clotting Assay2.535 (2.245 to 2.862)2.287 (2.010 to 2.601)
SecondaryCmax as Measured by Two-Stage Chromogenic Clotting Assay

Maximum measured concentration of rFVIIIFc.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU/dL
Cmax as Measured by Two-Stage Chromogenic Clotting Assay
IU/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Cmax as Measured by Two-Stage Chromogenic Clotting Assay132.61 (116.85 to 150.50)122.29 (106.80 to 140.03)
Secondaryt½ as Measured by Two-Stage Chromogenic Clotting Assay

Time required for the concentration of the drug to reach half of its original value.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · hours
t½ as Measured by Two-Stage Chromogenic Clotting Assay
hoursrFVIIIFc 1000 IUrFVIIIFc 3000 IU
t½ as Measured by Two-Stage Chromogenic Clotting Assay18.58 (16.35 to 21.12)19.10 (16.44 to 22.19)
SecondaryCL as Measured by Two-Stage Chromogenic Clotting Assay

The measure of the efficiency of the body to remove the drug and the unit is the volume of the plasma or blood cleared of drug per unit time.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · mL/h/kg
CL as Measured by Two-Stage Chromogenic Clotting Assay
mL/h/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
CL as Measured by Two-Stage Chromogenic Clotting Assay1.962 (1.665 to 2.311)2.006 (1.720 to 2.339)
SecondaryVss as Measured by Two-Stage Chromogenic Clotting Assay

The apparent volume of distribution at steady state. (Volume of distribution 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.)

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · mL/kg
Vss as Measured by Two-Stage Chromogenic Clotting Assay
mL/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Vss as Measured by Two-Stage Chromogenic Clotting Assay47.41 (43.01 to 52.26)51.27 (44.65 to 58.88)
SecondaryMRT as Measured by Two-Stage Chromogenic Clotting Assay

The average time at which the number of absorbed molecules reside in the body, after single-dose administration.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · hours
MRT as Measured by Two-Stage Chromogenic Clotting Assay
hoursrFVIIIFc 1000 IUrFVIIIFc 3000 IU
MRT as Measured by Two-Stage Chromogenic Clotting Assay24.17 (21.16 to 27.60)25.56 (22.15 to 29.50)
SecondaryTmax as Measured by Two-Stage Chromogenic Clotting Assay

Time at which maximum activity (Cmax) is observed.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · hours
Tmax as Measured by Two-Stage Chromogenic Clotting Assay
hoursrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Tmax as Measured by Two-Stage Chromogenic Clotting Assay0.61 (0.51 to 0.71)0.61 (0.52 to 0.72)
SecondaryAUClast as Measured by Two-Stage Chromogenic Clotting Assay

Area under the plasma concentration time-curve from zero to the last measured concentration.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU*h/dL
AUClast as Measured by Two-Stage Chromogenic Clotting Assay
IU*h/dLrFVIIIFc 1000 IUrFVIIIFc 3000 IU
AUClast as Measured by Two-Stage Chromogenic Clotting Assay2555.4 (2166.7 to 3013.9)2520.5 (2124.4 to 2990.5)
SecondaryLambda Z as Measured by Two-Stage Chromogenic Clotting Assay

First order rate constant associated with the terminal portion of the curve (lambda z).

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · 1/h
Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay
1/hrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Lambda Z as Measured by Two-Stage Chromogenic Clotting Assay0.03730 (0.03282 to 0.04239)0.03629 (0.03124 to 0.04216)
SecondaryAUCext as Measured by Two-Stage Chromogenic Clotting Assay

Percentage of AUCinf extrapolated from the last data point to infinity.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · percentage of AUCinf
AUCext as Measured by Two-Stage Chromogenic Clotting Assay
percentage of AUCinfrFVIIIFc 1000 IUrFVIIIFc 3000 IU
AUCext as Measured by Two-Stage Chromogenic Clotting Assay2.923 (2.106 to 4.057)2.965 (1.890 to 4.650)
SecondaryDNAUC as Measured by Two-Stage Chromogenic Clotting Assay

Dose normalized area under the FVIII activity-time curve.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · IU*h/dL per IU/kg
DNAUC as Measured by Two-Stage Chromogenic Clotting Assay
IU*h/dL per IU/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
DNAUC as Measured by Two-Stage Chromogenic Clotting Assay50.97 (43.27 to 60.05)49.85 (42.75 to 58.13)
SecondaryVz as Measured by Two-Stage Chromogenic Clotting Assay

The theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug.

Time frame:
Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection
Reported as:
Geometric mean · mL/kg
Vz as Measured by Two-Stage Chromogenic Clotting Assay
mL/kgrFVIIIFc 1000 IUrFVIIIFc 3000 IU
Vz as Measured by Two-Stage Chromogenic Clotting Assay52.59 (47.31 to 58.47)55.28 (47.12 to 64.84)
SecondaryDevelopment of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay

An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. An exact 95% confidence interval (CI) for the proportion of subjects with a confirmed inhibitor was calculated using the Clopper-Pearson method for a binomial proportion. Percentage of participants with confirmed inhibitor development was summarized overall.

Time frame:
Predose, Month 3, Month 6/early withdrawal. Additionally: If inhibitor suspected; at 10-15 EDs; 2-4 weeks prior to scheduled surgery; preoperatively on day of surgery; 1-2 weeks post-surgery; at last postoperative visit (last 2 for major surgery only)
Reported as:
Number · percentage of participants
Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay
percentage of participantsrFVIIIFc
Development of Inhibitor as Measured by the Nijmegen-Modified Bethesda Assay0 (0 to 17.65)

Adverse events

Collected over From screening (for serious adverse events) or first dose of study drug (for adverse events) until end of study (up to approximately 6 months).. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Total Active—2/19 (10.5%)12/19 (63.2%)
Most frequent serious events
Most frequent serious events
EventTotal Active
HydroceleCongenital, familial and genetic disorders1/19
ArthropathyMusculoskeletal and connective tissue disorders1/19
Most frequent other events
Showing 10 of 15
Most frequent other events
EventTotal Active
NasopharyngitisInfections and infestations2/19
Limb injuryInjury, poisoning and procedural complications2/19
AcneSkin and subcutaneous tissue disorders2/19
Tympanic membrane perforationEar and labyrinth disorders1/19
Abdominal discomfortGastrointestinal disorders1/19
InfluenzaInfections and infestations1/19
Oral herpesInfections and infestations1/19
Post procedural cellulitisInfections and infestations1/19
Upper respiratory tract infectionInfections and infestations1/19
ContusionInjury, poisoning and procedural complications1/19

Baseline characteristics

Age, Continuous
Age, Continuous(years)rFVIIIFc 1000 / 3000rFVIIIFc 3000 / 1000Total
Mean23 ± 12.4530.9 ± 19.7626.7 ± 16.35
Sex: Female, Male
Sex: Female, Male(Participants)rFVIIIFc 1000 / 3000rFVIIIFc 3000 / 1000Total
Female000
Male10919
08

Study locations

8 sites
  • Research Site
    Los Angeles, California, United States
  • Research Site
    Salt Lake City, Utah 84101, United States
  • Research Site
    Seattle, Washington, United States
  • Research Site
    Herston, Australia
  • Research Site
    Perth, Australia
  • Research Site
    Basingstoke, United Kingdom
  • Research Site
    Cambridge, United Kingdom
  • Research Site
    London, United Kingdom
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 19, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02083965
Lead sponsor
Bioverativ Therapeutics Inc.
Responsible party
Sponsor
First posted
Mar 11, 2014
Start date
Mar 2014
Primary completion
Oct 2014
Completion
May 2015
Results posted
Aug 19, 2016
Last update
Dec 19, 2020

Study contacts

Medical Director
study director · Bioverativ Therapeutics Inc.

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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