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History of Changes for Study: NCT03205163
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)
Latest version (submitted March 30, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 29, 2017 None (earliest Version on record)
2 August 29, 2017 Recruitment Status, Study Status, Contacts/Locations and Oversight
3 September 1, 2017 Study Status
4 October 13, 2017 Study Status and Contacts/Locations
5 October 17, 2017 Eligibility and Study Status
6 November 14, 2017 Study Status and Contacts/Locations
7 December 13, 2017 Study Status and Contacts/Locations
8 December 18, 2017 Eligibility, Outcome Measures and Study Status
9 February 2, 2018 Study Status and Contacts/Locations
10 July 13, 2018 Study Status and Oversight
11 September 13, 2018 Study Status
12 November 1, 2018 Study Status
13 December 17, 2018 Recruitment Status, Study Status, Contacts/Locations and Study Design
14 November 11, 2019 Outcome Measures, Study Status, Arms and Interventions, Sponsor/Collaborators, Study Identification, Document Section, Results, IPDSharing, Eligibility, Study Design and Study Description
15 December 15, 2020 Study Identification and Study Status
16 March 30, 2022 Study Status and IPDSharing
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Study NCT03205163
Submitted Date:  June 29, 2017 (v1)

Open or close this module Study Identification
Unique Protocol ID: 242HA101
Brief Title: 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)
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
Secondary IDs: 242HA101 [Bioverativ Therapeutics Inc]
Open or close this module Study Status
Record Verification: June 2017
Overall Status: Not yet recruiting
Study Start: August 2017
Primary Completion: August 2018 [Anticipated]
Study Completion: September 2018 [Anticipated]
First Submitted: June 29, 2017
First Submitted that
Met QC Criteria:
June 29, 2017
First Posted: July 2, 2017 [Actual]
Last Update Submitted that
Met QC Criteria:
June 29, 2017
Last Update Posted: July 2, 2017 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Bioverativ Therapeutics Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
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.
Detailed Description:
Open or close this module Conditions
Conditions: Hemophilia A
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Other
Study Phase: Phase 1/Phase 2
Interventional Study Model: Sequential Assignment
Number of Arms: 2
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 18 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of Participants With Adverse Events
[ Time Frame: Approximately 60 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: Approximately 60 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.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: Male
Gender Based:
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 (not including hepatitis or HIV) present within 30 days of screening
  • Other coagulation disorder(s) in addition to hemophilia A
  • History of hypersensitivity or anaphylaxis associated with any FVIII product
  • 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
Open or close this module Contacts/Locations
Central Contact Person: Bioverativ Therapeutics Inc, Waltham, MA, USA
Telephone: 1-888-794-1415
Email: clinicaltrials@bioverativ.com
Locations:
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Links:
Available IPD/Information:

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