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Completed

NCT Number: NCT02083965

Pharmacokinetics of rFVIIIFc at Two Vial Strengths

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.

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Key information

Conditions

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

Age range

12 year and older

Sex eligibility

Male

Study type

Interventional

Phase

Phase 1

Primary location

Research Site, Herston, Australia

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

rFVIIIFc

Biological

Administered as specified in the treatment arm.

Other names: Eloctate, antihemophilic factor [recombinant] FC fusion protein, recombinant coagulation factor VIII Fc fusion protein, efmoroctocog alfa, BIIB031, Elocta

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

    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

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

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

    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

    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.

Secondary outcomes

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

    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

    Maximum measured concentration of rFVIIIFc.

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

    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

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

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

    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

    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.

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

    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

    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.)

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

    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

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

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

    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

    Time at which maximum activity (Cmax) is observed.

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

    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

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

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

    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

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

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

    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

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

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

    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

    Dose normalized area under the FVIII activity-time curve.

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

    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

    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.

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

    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

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

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

    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

    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.

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

    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

    Maximum measured concentration of rFVIIIFc.

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

    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

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

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

    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

    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.

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

    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

    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.)

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

    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

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

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

    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

    Time at which maximum activity (Cmax) is observed.

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

    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

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

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

    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

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

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

    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

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

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

    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

    Dose normalized area under the FVIII activity-time curve.

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

    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

    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.

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

    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)

    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.

Sponsors and collaborators

Lead sponsor

Bioverativ Therapeutics Inc.

Industry

Registry information

Official study title

A Randomized, Open-Label, Crossover Study to Evaluate the Pharmacokinetics of 2 Vial Strengths of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in Previously Treated Subjects With Severe Hemophilia A

Important dates

Study start
2014
Primary completion
2014
Study completion
2015
First posted
Mar 11, 2014
Registry last updated
Dec 19, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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