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BAX 855 Previously Untreated Patient (PUP)

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ClinicalTrials.gov Identifier: NCT02615691
Recruitment Status : Recruiting
First Posted : November 26, 2015
Last Update Posted : April 23, 2018
Sponsor:
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Brief Summary:
The purpose of this study is to investigate safety, immunogenicity and hemostatic efficacy of PEGylated recombinant FVIII (BAX 855) in previously untreated patients (PUPs) < 6 years of age with severe hemophilia A (baseline FVIII level < 1%) and < 3 EDs to ADVATE, BAX 855 or plasma transfusion.

Condition or disease Intervention/treatment Phase
Hemophilia A Biological: PEGylated Recombinant Factor VIII Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 3, Prospective, Multi-center, Open Label Study to Investigate Safety, Immunogenicity, and Hemostatic Efficacy of PEGylated Factor VIII (BAX 855) in Previously Untreated Patients (PUPs) and Minimally Treated Patients (MTPs) < 6 Years With Severe Hemophilia A (FVIII < 1%)
Actual Study Start Date : November 12, 2015
Estimated Primary Completion Date : June 29, 2023
Estimated Study Completion Date : June 29, 2023


Arm Intervention/treatment
Experimental: Previously untreated patients (PUPs)
<6 years of age with severe hemophilia A (baseline Factor VIII (FVIII) level < 1%)
Biological: PEGylated Recombinant Factor VIII
Polyethylene glycol (PEG)-ylated full-length recombinant FVIII (rFVIII)
Other Names:
  • ADYNOVATE
  • BAX855
  • BAX 855




Primary Outcome Measures :
  1. Incidence of FVIII inhibitor development [ Time Frame: Throughout Part A of the study, approximately 5 years ]
  2. Success rate of Immune tolerance induction (ITI) [ Time Frame: Up to 33 months ]

Secondary Outcome Measures :
  1. Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies [ Time Frame: Throughout Part A of the study, approximately 5 years ]
    Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG)

  2. Clinically significant adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Throughout Part A and Part B of the study, approximately 7 years ]
  3. Clinically significant changes in vital signs [ Time Frame: Throughout Part A and Part B of the study, approximately 7 years ]
  4. Clinically significant changes in clinical laboratory parameters [ Time Frame: Throughout Part A and Part B of the study, approximately 7 years ]
  5. Annualized bleeding rate (ABR) for prophylactic and on-demand treatment [ Time Frame: Throughout Part A of the study, approximately 5 years ]
  6. Number of BAX 855 infusions per bleeding episode [ Time Frame: Throughout Part A of the study, approximately 5 years ]
  7. Overall hemostatic efficacy rating [ Time Frame: 24 h after initiation of treatment and at resolution of bleed ]
  8. Weight-adjusted consumption of BAX 855 per month, per year and per event [ Time Frame: Throughout Part A of the study, approximately 5 years ]
  9. Number of infusions per month and per year [ Time Frame: Throughout Part A of the study, approximately 5 years ]
  10. Assessment of intra-, post- and perioperative hemostatic efficacy in case of surgery [ Time Frame: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first) ]
  11. Intra- and postoperative blood loss in case of surgery [ Time Frame: Surgery Day 0 up to postoperative Day 14 or discharge (whichever occurs first) ]
  12. Pharmacokinetics- Incremental recovery (IR) at baseline and over time [ Time Frame: Pre-infusion within 30 minutes; and post-infusion at 15-30 minutes and 24-48 hours ]
  13. Pharmacokinetics- Half-life (T1/2) at baseline (optional) [ Time Frame: Post-infusion: 15-30 minutes and 24-48 hours ]
  14. Immune tolerance induction (ITI) - Rate of partial success and failure of ITI [ Time Frame: Up to 33 months ]
  15. Immune tolerance induction (ITI) - annualized bleeding rate (ABR) during ITI [ Time Frame: Up to 33 months ]
  16. Immune tolerance induction (ITI) - Weight-adjusted consumption of BAX 855 per month and per year for each ITI regimen employed [ Time Frame: Up to 33 months ]
  17. Immune tolerance induction (ITI) - Catheter-related complications [ Time Frame: Up to 33 months ]
  18. Immune tolerance induction (ITI) -Binding Immunoglobulin G (IgG) and Immunoglobulin M (IgM) antibodies [ Time Frame: Up to 33 months ]
    Binding IgG and IgM antibodies to Factor VIII (FVIII), Factor VIII-Polyethylene glycol (PEG-FVIII) and Polyethylene glycol (PEG)



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 5 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Participant is < 6 years old at the time of screening
  2. Participant is previously untreated with < 3 exposure days (EDs) to ADVATE, BAX 855 or plasma transfusion at any time prior to screening
  3. Participant has severe hemophilia A (Factor VIII (FVIII) < 1%) as determined by the central laboratory, or a historical FVIII level < 1% as determined at any local laboratory, optionally supported by an additional FVIII gene mutation consistent with severe hemophilia A
  4. Participant is immune competent with a CD4+ count > 200 cells/mm^3, as confirmed by the central laboratory at screening
  5. Parent or legally authorized representative is willing and able to comply with the requirements of the protocol

Additional inclusion criteria for Part B (immune tolerance induction (ITI))

  1. Parent or legal representative has/have voluntarily provided signed informed consent for ITI portion
  2. Participant has a confirmed positive high titer inhibitor (> 5.00 Bethesda unit (BU)) or has a positive confirmed low titer inhibitor (≥ 0.6 BU) as determined by the central laboratory based on a second repeat blood sample with

    1. poorly controlled bleeding despite increased BAX 855 doses, or
    2. requires bypassing agents to treat bleeding

Exclusion Criteria

  1. Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening
  2. Participant has a history of FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening
  3. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease)
  4. Participant has been previously treated with any type of FVIII concentrate other than ADVATE or BAX 855, or was administered ADVATE, BAX 855 or plasma transfusion for ≥ 3 EDs at any time prior to screening
  5. Participant receives >2 EDs of ADVATE in total during the periods prior to enrollment and during the screening period, until the baseline infusion.
  6. The participant's weight is anticipated to be < 5 kg at the baseline visit
  7. Participant's platelet count is < 100,000/mL
  8. Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG) or Tween 80
  9. Participant has severe chronic hepatic dysfunction [eg, > 5 times upper limit of normal alanine aminotransferase (ALT), aspartate aminotransferase (AST), or a documented international normalized ratio (INR) > 1.5] in his medical history or at the time of screening
  10. Participant has severe renal impairment (serum creatinine > 1.5 times the upper limit of normal)
  11. Participant has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or is scheduled to use such drugs during study participation
  12. Participant is scheduled to receive during the course of the study a systemic immunomodulating drug (e.g. corticosteroid agents at a dose equivalent to hydrocortisone greater than 10 mg/day or α-interferon) other than anti-retroviral chemotherapy
  13. Participant has participated in another clinical study involving an investigational product (IP) 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
  14. Parent or legally authorized representative has a medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance
  15. Parent, legally authorized representative or participant are a member of the team conducting this study or is in a dependent relationship with one of the study team members. Dependent relationships include close relatives (ie, children, partner/spouse, siblings, parents) as well as employees of the investigator or site personnel conducting the study.

Additional exclusion criteria for Part B (ITI)

  1. Spontaneous disappearance of the inhibitor prior to ITI
  2. FVIII inhibitor titer ≥ 0.6 BU is not confirmed by a second new blood sample and determined at the central laboratory
  3. Inability or unwillingness to comply with the protocol

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): NCT02615691


Contacts
Contact: Celine Kefurt +431201002476205 celine.kefurt@baxalta.com

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Sponsors and Collaborators
Baxalta now part of Shire
Investigators
Study Director: William Savage, MD, PhD Baxalta now part of Shire

Responsible Party: Baxalta now part of Shire
ClinicalTrials.gov Identifier: NCT02615691     History of Changes
Other Study ID Numbers: 261203
First Posted: November 26, 2015    Key Record Dates
Last Update Posted: April 23, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: 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