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Trial record 1 of 1 for:    BIVV001 hemophilia | Hemophilia A
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A Safety, Tolerability, and Pharmacokinetics Study of a Single Intravenous Injection of Recombinant Coagulation Factor VIII Fc - Von Willebrand Factor - XTEN Fusion Protein (rFVIIIFc-VWF-XTEN) (BIVV001) in Previously Treated Adults With Severe Hemophilia A (EXTEN-A)

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ClinicalTrials.gov Identifier: NCT03205163
Recruitment Status : Completed
First Posted : July 2, 2017
Last Update Posted : December 18, 2018
Sponsor:
Information provided by (Responsible Party):
Bioverativ Therapeutics Inc.

Brief Summary:
The primary purpose is to assess the safety and tolerability of a single intravenous (IV) administration of BIVV001 in adult previously treated patients (PTPs) with severe hemophilia A.

Condition or disease Intervention/treatment Phase
Hemophilia A Biological: Recombinant FVIII (rFVIII) (Low Dose) Biological: rFVIII (High Dose) Biological: BIVV001 (Low Dose) Biological: BIVV001 (High Dose) Phase 1 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1/2a, Open-Label, Dose-Escalation Study to Determine the Safety, Tolerability, and Pharmacokinetics of a Single Intravenous Injection of rFVIIIFc-VWF-XTEN (BIVV001) in Previously Treated Adults With Severe Hemophilia A
Actual Study Start Date : July 31, 2017
Actual Primary Completion Date : November 12, 2018
Actual Study Completion Date : November 12, 2018


Arm Intervention/treatment
Experimental: Low-Dose Cohort: Recombinant FVIII (rFVIII) and BIVV001
Participants will receive a single intravenous (IV) low dose of recombinant coagulation factor VIII (rFVIII) followed by a washout period of at least 72-hour, then a single IV low dose of BIVV001.
Biological: Recombinant FVIII (rFVIII) (Low Dose)
Participants will receive a single IV low dose of rFVIII.

Biological: BIVV001 (Low Dose)
Participants will receive single IV low dose of BIVV001.

Experimental: High-Dose Cohort: rFVIII and BIVV001
Participants will receive a single IV high dose of rFVIII, followed by a washout period of at least 96-hour, then a single IV high dose of BIVV001.
Biological: rFVIII (High Dose)
Participants will receive a single IV high dose of rFVIII.

Biological: BIVV001 (High Dose)
Participants will receive single IV high dose of BIVV001.




Primary Outcome Measures :
  1. Number of Participants With Adverse Events [ Time Frame: Up to 156 days ]
    An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

  2. Percentage of Participants With Clinically Significant Laboratory Abnormalities [ Time Frame: Up to 156 days ]
    Clinically significant laboratory abnormalities including hematology, clinical chemistry, urinalysis, coagulation, thrombosis markers, and development of inhibitors (neutralizing antibodies directed against FVIII) as determined via the Nijmegen-modified Bethesda Assay (an inhibitor test result greater than or equal to (>=) 0.6 Bethesda units (BU)/milliliter (mL), confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive).


Secondary Outcome Measures :
  1. Maximum Observed Plasma Concentration (Cmax) of Recombinant FVIII (rFVIII) [ Time Frame: up to 72 hours post dose ]
    The Cmax is the maximum observed plasma concentration.

  2. Half life (t1/2) of rFVIII [ Time Frame: up to 72 hours post dose ]
    Time required for the concentration of the drug to reach half of its original value.

  3. Clearance (CL) of rFVIII [ Time Frame: up to 72 hours post dose ]
    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. Apparent Volume of Distribution at Steady State (Vss) of rFVIII [ Time Frame: up to 72 hours post dose ]
    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. Area Under the Plasma Concentration Time Curve From Time Zero to Infinity Time (AUC [0-Infinity]) of rFVIII [ Time Frame: up to 72 hours post dose ]
    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity).

  6. Mean Residence Time (MRT) of rFVIII [ Time Frame: up to 72 hours post dose ]
    The average time at which the number of absorbed molecules reside in the body, after single-dose administration.

  7. Incremental Recovery (IR) of rFVIII [ Time Frame: up to 72 hours post dose ]
    Incremental Recovery is defined as the increase in the circulating FVIII activity level for one unit (IU) of the FVIII product per kilogram body weight.

  8. Time to 1 Percent (%) Above Baseline for FVIII Activity of rFVIII [ Time Frame: up to 72 hours post dose ]
    Time to 1% activity is the time required from the start of dosing for the FVIII activity to reach 1 IU/dL (1%) above their baseline levels.

  9. Maximum Observed Plasma Concentration (Cmax) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    The Cmax is the maximum observed plasma concentration.

  10. Half life (t1/2) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    Time required for the concentration of the drug to reach half of its original value.

  11. Clearance (CL) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    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.

  12. Apparent Volume of Distribution at Steady State (Vss) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    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.

  13. Area Under the Plasma Concentration Time Curve From Time Zero to Infinity Time (AUC [0-Infinity]) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-infinity).

  14. Mean Residence Time (MRT) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    The average time at which the number of absorbed molecules reside in the body, after single-dose administration.

  15. Incremental Recovery (IR) of BIVV001 [ Time Frame: up to 336 hours postdose ]
    Incremental Recovery is defined as the increase in the circulating FVIII activity level for one unit (IU) of the FVIII product per kilogram body weight.

  16. Time to 1 Percent Above Baseline for FVIII Activity of BIVV001 [ Time Frame: up to 336 hours postdose ]
    Time to 1% activity is the time required from the start of dosing for the FVIII activity to reach 1 IU/dL (1%) above their baseline levels.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ability of the participant, or his legally authorized representative (e.g., parent or legal guardian) if applicable in accordance with local regulations, to understand the purpose and risks of the study and provide signed and dated informed consent/assent and authorization to use confidential health information in accordance with national and local participant privacy regulations
  • Severe hemophilia A, defined as less than (<) 1 international units per deciliter (IU/dL) (<1 percent [%]) endogenous FVIII at screening as determined by the one-stage clotting assay from the central laboratory. If the initial screening result is greater than or equal to (>=) 1%, then a repeat endogenous FVIII activity level will be performed using the using the one stage clotting assay from the central laboratory. If the repeated result is < 1 IU/dL (<1%), then the participant will meet this inclusion requirement
  • Previous treatment for hemophilia A, defined as at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products at Day 1. Fresh frozen plasma treatment must not be considered in the count for documented exposure days
  • Platelet count >=100,000 cells/ microliter (mcL) at screening (test performed by the central laboratory and reviewed prior to the Day 1 Recombinant FVIII (rFVIII) dose)
  • A participant known to be human immunodeficiency virus (HIV) antibody positive, either previously documented or identified from screening assessments, must have the following results prior to Day 1 rFVIII dose: cluster of differentiation 4 (CD4) lymphocyte count greater than (>) 200 cells/millimeter (mm)^3; viral load of <400 copies/mL

Exclusion Criteria:

Medical History:

  • Any concurrent clinically significant major disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment
  • Serious active bacterial or viral infection (other than chronic hepatitis or HIV) present within 30 days of screening
  • Other known coagulation disorder(s) in addition to hemophilia A
  • History of hypersensitivity or anaphylaxis associated with any FVIII product
  • Known or suspected allergy to mice, hamsters, or any ingredient in recombinant FVIII
  • History of a positive inhibitor test or clinical signs of decreased response to FVIII administrations. Family history of inhibitors will not exclude the participant

Medications and Procedures:

- Current enrollment or participation within 30 days prior to screening in any other investigational study

Other:

  • Inability to comply with study requirements as assessed by the Investigator
  • Other unspecified reasons that, in the opinion of the Investigator or Sponsor, make the participant unsuitable for enrollment

Information from the National Library of Medicine

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): NCT03205163


Locations
United States, California
University of California Los Angeles Medical Center
Los Angeles, California, United States, 90007
United States, Indiana
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, United States, 46260
United States, Iowa
University of Iowa Hospitals & Clinics
Iowa City, Iowa, United States, 52242
United States, Michigan
Michigan State University
East Lansing, Michigan, United States, 48823
United States, Mississippi
Mississippi Center for Advanced Medicine
Madison, Mississippi, United States, 39110
United States, Pennsylvania
Hemophilia Center of Western PA
Pittsburgh, Pennsylvania, United States, 15213
United States, Washington
University of Washington
Seattle, Washington, United States, 98104
Japan
Nara Medical University Hospital
Kashihara-Shi, Nara-Ken, Japan, 634-8521
Tokyo Medical University Hospital
Shinjuku-Ku, Tokyo-To, Japan, 160-0023
Ogikubo Hospital
Tokyo, Tokyo-To, Japan, 167-8515
Sponsors and Collaborators
Bioverativ Therapeutics Inc.

Responsible Party: Bioverativ Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT03205163     History of Changes
Other Study ID Numbers: 242HA101
242HA101 ( Other Identifier: Bioverativ Therapeutics Inc )
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: December 18, 2018
Last Verified: December 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Hemophilia A
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants