ClinicalTrials.gov
ClinicalTrials.gov Menu

BAX 111 rVWF in Pediatrics

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02932618
Recruitment Status : Recruiting
First Posted : October 13, 2016
Last Update Posted : February 19, 2018
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:

The purpose of this study in pediatric participants (<18 years of age) with severe hereditary von Willebrand disease (VWD) is:

  1. To assess the efficacy, safety, and tolerability of recombinant von Willebrand Factor (rVWF), with or without ADVATE, in the treatment and control of nonsurgical bleeding events
  2. To assess the efficacy and safety of rVWF with ADVATE during elective or emergency surgery
  3. To determine the pharmacokinetic (PK) profile of rVWF

Condition or disease Intervention/treatment Phase
Von Willebrand Disease Biological: von Willebrand factor (Recombinant) Biological: Antihemophilic Factor (Recombinant) Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Prospective, Multicenter, Uncontrolled, Open-Label Clinical Study to Determine the Efficacy, Safety, and Tolerability of rVWF With or Without ADVATE in the Treatment and Control of Bleeding Episodes, the Efficacy and Safety of rVWF in Elective and Emergency Surgeries, and the Pharmacokinetics (PK) of rVWF in Children Diagnosed With Severe Von Willebrand Disease
Actual Study Start Date : December 18, 2017
Estimated Primary Completion Date : May 29, 2020
Estimated Study Completion Date : May 29, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: On-demand Treatment
Participants will receive treatment for non-surgical bleeding episodes.
Biological: von Willebrand factor (Recombinant)
Lyophilized powder and solvent to prepare solution for injection.
Other Names:
  • VONVENDI
  • rVWF
  • BAX111
  • BAX 111

Biological: Antihemophilic Factor (Recombinant)
Packaged in single boxes with 2 glass vials, with one vial containing the lyophilized ADVATE and the second vial containing the diluent.
Other Names:
  • ADVATE
  • Recombinant Factor VIII
  • rFVIII

Experimental: Elective Surgery
12-24 hours prior to surgery and within 3 hours of surgery. Minor surgery: infuse every 12-24 hours for at least 48 hours. Oral Surgery: infuse at least once within first 8-12 hours post-surgery. Major Surgery: infuse every 12-24 hours for at least first 72 hours post-surgery.
Biological: von Willebrand factor (Recombinant)
Lyophilized powder and solvent to prepare solution for injection.
Other Names:
  • VONVENDI
  • rVWF
  • BAX111
  • BAX 111

Biological: Antihemophilic Factor (Recombinant)
Packaged in single boxes with 2 glass vials, with one vial containing the lyophilized ADVATE and the second vial containing the diluent.
Other Names:
  • ADVATE
  • Recombinant Factor VIII
  • rFVIII

Experimental: Emergency Surgery
Within 3 hours prior to surgery. Minor surgery: infuse every 12-24 hours for at least 48 hours. Oral Surgery: infuse at least once within first 8-12 hours post-surgery. Major Surgery: infuse every 12-24 hours for at least first 72 hours post-surgery.
Biological: von Willebrand factor (Recombinant)
Lyophilized powder and solvent to prepare solution for injection.
Other Names:
  • VONVENDI
  • rVWF
  • BAX111
  • BAX 111

Biological: Antihemophilic Factor (Recombinant)
Packaged in single boxes with 2 glass vials, with one vial containing the lyophilized ADVATE and the second vial containing the diluent.
Other Names:
  • ADVATE
  • Recombinant Factor VIII
  • rFVIII




Primary Outcome Measures :
  1. Hemostatic efficacy [ Time Frame: Within 24 hours of the beginning of a bleeding episode (BE) ]
    Treatment success for rVWF-treated nonsurgical bleeding episodes (using a 4-point scale: Excellent, Good, Moderate, None)


Secondary Outcome Measures :
  1. Number of treated nonsurgical bleeding episodes with an efficacy rating of 'excellent' or 'good' [ Time Frame: Within 24 hours of the beginning of a bleeding episode (BE) ]
  2. Number of infusions per bleeding episode [ Time Frame: Within 24 hours of the beginning of a bleeding episode (BE) ]
  3. Number of rVWF units per bleeding episode [ Time Frame: Within 24 hours of the beginning of a bleeding episode (BE) ]
  4. Number of ADVATE units (if needed), per bleeding episode [ Time Frame: Within 24 hours of the beginning of a bleeding episode (BE) ]
  5. Elective surgery: overall assessment of hemostatic efficacy 24 hours after the last perioperative infusion of rVWF [ Time Frame: 24 hours after the last perioperative infusion of rVWF ]
    Assessed by the Investigator (hematologist) on a 4-point ordinal scale: Excellent, Good, Moderate, None

  6. Incidence and severity of adverse events (AEs) by system organ class (SOC) and preferred term [ Time Frame: Throughout the study period of approximately 2 years, 9 months ]
  7. Incidence of thrombotic events [ Time Frame: Throughout the study period of approximately 2 years, 9 months ]
  8. Incidence of severe hypersensitivity reactions [ Time Frame: Throughout the study period of approximately 2 years, 9 months ]
  9. Development of neutralizing antibodies to VWF and FVIII [ Time Frame: Throughout the study period of approximately 2 years, 9 months ]
  10. Development of total binding antibodies to VWF [ Time Frame: Throughout the study period of approximately 2 years, 9 months ]
  11. Development of antibodies to CHO proteins, murine IgG, and rFurin [ Time Frame: Throughout the study period of approximately 2 years, 9 months ]
  12. Pharmacokinetics: Area under the plasma concentration/time curve from 0 to 96 hours post-infusion (AUC0-96h) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  13. Pharmacokinetics: Area under the plasma concentration/time curve from time 0 to infinity (AUC0-∞) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  14. Pharmacokinetics: Mean residence time (MRT) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  15. Pharmacokinetics: Clearance (CL) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  16. Incremental recovery (IR) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  17. In-vivo recovery (IVR) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  18. Elimination phase half-life (T1/2) [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  19. Volume of distribution at steady state (Vss) for VWF:RCo [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
  20. Area under the plasma concentration/time curve from 0 to 96 hours post-infusion (AUC0-96h) for VWF:Ag and VWF:CB [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]
    von Willebrand factor: antigen (VWF:Ag); von Willebrand factor: collagen binding capacity (VWF:CB)

  21. Area under the plasma concentration/time curve from 0 to 96 hours post-infusion (AUC0-96h) for Factor VIII (FVIII) activity [ Time Frame: Within 30 minutes prior to infusion and post infusion at: SEQUENCE 1: 1, 2, 72 hours; SEQUENCE 2: 15 minutes, 12, and 48 hours; SEQUENCE 3: 6, 30, and 96 hours ]


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:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of severe von Willebrand disease (VWD) (defined as von Willebrand factor: ristocetin cofactor [VWF:RCo] <20%):

    1. Type 1 (VWF:RCo <20 IU/dL); or
    2. Type 2A (VWF:RCo <20 IU/dL), Type 2B (as diagnosed by genotype), Type 2N (Factor VIII coagulation activity [FVIII:C] <10% and historically documented genetics), Type 2M; or
    3. Type 3 (VWF:Ag ≤3 IU/dL).
  2. Age 0 to <18 years at the time of Screening
  3. The participant has provided assent (if appropriate) and legally authorized representative(s) has provided informed consent
  4. If female of childbearing potential, participant presents with a negative serum pregnancy test
  5. If applicable, participant agrees to employ adequate birth control measures for the duration of the study
  6. The participant and/or the legal representative is willing and able to comply with the requirements of the protocol

Additional inclusion criteria for previously treated participants and participants undergoing surgery are as follows:

  1. Unable to tolerate or are inadequately responsive to deamino-delta-D-arginine vasopressin
  2. The participant has had a minimum of 1 documented bleed requiring VWF coagulation factor replacement therapy during the previous 12 months prior to enrollment and overall historically 3 or more exposure days (EDs) to plasma-derived VWF

Additional inclusion criterion for previously untreated participants are as follows:

1. The participant has not received prior VWF coagulation factor replacement therapy

Exclusion Criteria:

  1. Diagnosis of pseudo-VWD or another hereditary or acquired coagulation disorder (eg, qualitative and quantitative platelet disorders or elevated prothrombin time [PT]/international normalized ratio [INR] >1.4)
  2. History or presence of a VWF inhibitor at Screening
  3. History or presence of a Factor VIII (FVIII) inhibitor with a titer ≥0.4 Bethesda units (BU) (by Nijmegen assay) or ≥0.6 BU (by Bethesda assay)
  4. Documented history of a VWF:RCo half-life <6 hours
  5. Known hypersensitivity to any of the components of the study drug, such as mouse or hamster proteins
  6. Medical history of immunological disorders, excluding seasonal allergic rhinitis/conjunctivitis/asthma, food allergies, or animal allergies
  7. Medical history of a thromboembolic event
  8. Human immunodeficiency virus (HIV) positive, with an absolute CD4 count <200/mm^3
  9. In the judgment of the Investigator, the participant has another clinically significant concomitant disease (eg, uncontrolled hypertension, cancer) that may pose additional risks for the participant
  10. Diagnosis of significant liver disease, as evidenced by, but not limited to, any of the following: serum alanine aminotransferase (ALT) of 5 times the upper limit of normal; hypoalbuminemia; portal vein hypertension (eg, presence of otherwise unexplained splenomegaly, history of esophageal varices) or liver cirrhosis classified as Child B or C
  11. Diagnosis of renal disease, with a serum creatinine level ≥2.5 mg/dL
  12. Immunomodulatory drug treatment other than anti-retroviral chemotherapy (eg, α-interferon, or corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day (excluding topical treatment [eg, ointments, nasal sprays]), within 30 days prior to signing the informed consent (or assent, if appropriate)
  13. If female, participant is pregnant or lactating at the time informed consent (or assent, if appropriate) is obtained
  14. Participant has participated in another clinical study involving an investigational product (IP), other than recombinant von Willebrand Factor (rVWF) with or without ADVATE, or investigational device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an IP or investigational device during the course of this study

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): NCT02932618


Contacts
Contact: Sanhita Abrol, PhD +1 617-588-8550 sanhita.abrol1@shire.com

  Show 38 Study Locations
Sponsors and Collaborators
Baxalta now part of Shire
Investigators
Study Director: Arthur Sytkowski, MD Baxalta now part of Shire

Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02932618     History of Changes
Other Study ID Numbers: 071102
2016-001477-33 ( EudraCT Number )
First Posted: October 13, 2016    Key Record Dates
Last Update Posted: February 19, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Von Willebrand Diseases
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Coagulation Protein Disorders
Blood Platelet Disorders
Hemorrhagic Disorders
Genetic Diseases, Inborn
Factor VIII
Coagulants