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BAX 802 in CHA With Inhibitors

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ClinicalTrials.gov Identifier: NCT02895945
Recruitment Status : Recruiting
First Posted : September 12, 2016
Last Update Posted : April 8, 2019
Sponsor:
Collaborator:
Baxalta Innovations GmbH, now part of Shire
Information provided by (Responsible Party):
Shire ( Baxalta now part of Shire )

Tracking Information
First Submitted Date  ICMJE August 15, 2016
First Posted Date  ICMJE September 12, 2016
Last Update Posted Date April 8, 2019
Actual Study Start Date  ICMJE May 10, 2017
Estimated Primary Completion Date April 2, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
  • Global Hemostatic Efficacy Assessment score (GHEA)- composed of 3 individual ratings: Day 0 [ Time Frame: Day 0 ]
    GHEA=Sum of 1-3 ratings. Excellent: 7-9 (no category <2) Good: 5-7 (no category <1) Fair: 3-4 (no category <1) None 0-2 (≥ category 0). a. Intra operative hemostatic efficacy (Excellent=3: Good=2: Fair=1: None =0). b. Hemostatic efficacy postoperative Day 1 (Excellent=3: Good=2: Fair=1: None =0). c. Overall perioperative hemostatic efficacy at discharge or within 24 to 72 hours after last perioperative treatment dose of BAX 802 (whichever is earlier) (Excellent=3: Good=2: Fair=1: None =0)
  • Global Hemostatic Efficacy Assessment score (GHEA)- composed of 3 individual ratings: Day 1 [ Time Frame: Day 1 ]
    GHEA=Sum of 1-3 ratings. Excellent: 7-9 (no category <2) Good: 5-7 (no category <1) Fair: 3-4 (no category <1) None 0-2 (≥ category 0). a. Intra operative hemostatic efficacy (Excellent=3: Good=2: Fair=1: None =0). b. Hemostatic efficacy postoperative Day 1 (Excellent=3: Good=2: Fair=1: None =0). c. Overall perioperative hemostatic efficacy at discharge or within 24 to 72 hours after last perioperative treatment dose of BAX 802 (whichever is earlier) (Excellent=3: Good=2: Fair=1: None =0)
  • Global Hemostatic Efficacy Assessment score (GHEA)- composed of 3 individual ratings: At discharge or within 24 to 72 hours after last perioperative treatment dose of BAX 802 (whichever is earlier) [ Time Frame: At discharge or within 24 to 72 hours after last perioperative treatment dose of BAX 802 (whichever is earlier) ]
    GHEA=Sum of 1-3 ratings. Excellent: 7-9 (no category <2) Good: 5-7 (no category <1) Fair: 3-4 (no category <1) None 0-2 (≥ category 0). a. Intra operative hemostatic efficacy (Excellent=3: Good=2: Fair=1: None =0). b. Hemostatic efficacy postoperative Day 1 (Excellent=3: Good=2: Fair=1: None =0). c. Overall perioperative hemostatic efficacy at discharge or within 24 to 72 hours after last perioperative treatment dose of BAX 802 (whichever is earlier) (Excellent=3: Good=2: Fair=1: None =0)
Original Primary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
Global Hemostatic Efficacy Assessment score (GHEA)- composed of 3 individual ratings [ Time Frame: Day 0, Day 1, and postoperative (postop) day 14 or discharge (whichever is earlier) ]
GHEA=Sum of 1-3 ratings. Excellent: 7-9 (no category <2) Good: 5-7 (no category <1) Fair: 3-4 (no category <1) None 0-2 (≥ category 0). a. Intra operative hemostatic efficacy (Excellent=3: Good=2: Fair=1: None =0). b. Hemostatic efficacy postoperative Day 1 (Excellent=3: Good=2: Fair=1: None =0). c. Overall perioperative hemostatic efficacy at discharge or ≤ day 14 (Excellent=3: Good=2: Fair=1: None =0)
Change History Complete list of historical versions of study NCT02895945 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 11, 2018)
  • Intra- and post-operative blood loss compared to the estimated volume of expected average blood loss in a comparable healthy individual [ Time Frame: End of surgery; approximately 24 hours after surgery; and at discharge or 24 to 72 hours after the last perioperative treatment dose of BAX 802 (whichever is earlier) ]
    Predicted preoperatively by the investigator/surgeon
  • Intra- and post-operative blood loss compared to the expected maximum blood loss in a comparable healthy individual [ Time Frame: End of surgery; approximately 24 hours after surgery; and at discharge or 24 to 72 hours after the last perioperative treatment dose of BAX 802 (whichever is earlier) ]
    Predicted preoperatively by the investigator/surgeon
  • Major surgeries with good or excellent hemostatic score [ Time Frame: Day 0 (day of surgery) thru Day 14 or discharge (whichever is earlier) ]
    Proportion of major surgeries with good or excellent hemostatic score
  • Daily weight-adjusted administration of BAX 802 [ Time Frame: Day 0 (postoperative) thru Day 14 or discharge (whichever is earlier) ]
    Daily weight-adjusted administration of BAX 802 per participant
  • Total weight-adjusted administration of BAX 802 [ Time Frame: Day 0 (postoperative) thru Day 14 or discharge (whichever is earlier) ]
    Total weight-adjusted administration of BAX 802 per participant
  • Volume of blood products transfused [ Time Frame: From initiation of the surgery until Day 14 or discharge (whichever is earlier) ]
    Amount of blood products (e.g., whole blood, red blood cells, platelets, and plasma) transfused
  • Development of, and changes to, the titer of inhibitory and binding antibodies to porcine factor VIII (pFVIII) [ Time Frame: >14 days prior to Day 0 (surgery day); 7-14 days after last perioperative treatment dose of BAX 802; and day 42 after last perioperative treatment dose of BAX 802 ]
    Development of, and changes to, the titer of inhibitory and binding antibodies (IgG and IgM) to porcine factor VIII (pFVIII)
  • Development of, and changes to, the titer of inhibitory and binding antibodies to human factor VIII (hFVIII) [ Time Frame: >14 days prior to Day 0 (surgery day); 7-14 days after last perioperative treatment dose of BAX 802; and day 42 after last perioperative treatment dose of BAX 802 ]
    Development of, and changes to, the titer of inhibitory and binding antibodies (IgG and IgM) to human factor VIII (hFVIII)
  • Binding antibodies to baby hamster kidney (BHK) proteins [ Time Frame: ≤45 days prior to Day 0 (surgery day); 7-14 days after last perioperative treatment dose of BAX 802; and day 42 after last perioperative treatment dose of BAX 802 ]
    Development of binding antibodies to baby hamster kidney (BHK) proteins
  • Thrombo-embolic events [ Time Frame: Day 0 (surgery day) through end of study visit (day 42 after discharge) ]
    Occurrence of thrombo-embolic events
  • Incidence of severe allergic reactions [ Time Frame: Day 0 (surgery day) through end of study visit (day 42 after discharge) ]
    Incidence of severe allergic reactions (eg, anaphylaxis)
  • Other investigational product (IP)-related adverse events (AEs) [ Time Frame: From Day 0 (day of surgery) through Day 42 post-surgery (End of Study Visit) ]
    Incidence of other investigational product (IP)-related adverse events (AEs)
  • Clinically significant changes in vital signs [ Time Frame: Within 30 minutes pre, and 30 minutes post-dose ]
    Incidence of clinically significant changes in vital signs
  • Clinically significant changes in routine laboratory parameters - hematology labs [ Time Frame: Screening visit (up to 45 days prior to day of surgery (Day 0)) through End of Study Visit (Day 42 post-surgery) ]
    Incidence of clinically significant changes in routine laboratory parameters - hematology labs
  • Clinically significant changes in routine laboratory parameters - clinical chemistry [ Time Frame: Screening visit (up to 45 days prior to day of surgery (Day 0)) through End of Study Visit (Day 42 post-surgery) ]
    Incidence of clinically significant changes in routine laboratory parameters - clinical chemistry
Original Secondary Outcome Measures  ICMJE
 (submitted: September 6, 2016)
  • Blood loss compared to the estimated volume of expected average blood in a comparable healthy individual [ Time Frame: End of surgery; approximately 24 hours after surgery; and Day 14 or discharge (whichever is earlier) ]
    Predicted preoperatively by the investigator/surgeon
  • Blood loss compared to the estimated volume of expected maximum blood loss in a comparable healthy individual [ Time Frame: End of surgery; approximately 24 hours after surgery; and Day 14 or discharge (whichever is earlier) ]
    Predicted preoperatively by the investigator/surgeon
  • Occurrence of bleeding episodes [ Time Frame: Day 0 (day of surgery) thru Day 14 or discharge (whichever is earlier) ]
    During the intra- and postoperative periods and additional need for surgical intervention
  • Efficacy of the treatment of unrelated bleeding episodes in the postoperative period [ Time Frame: Day 0 (postoperative) thru Day 14 or discharge (whichever is earlier) ]
    Rating Scale for Treatment of Unrelated BEs (4-point ordinal scale): • Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion. No additional infusion required for the control of bleeding. Administration of further infusions to maintain hemostasis would not affect this scoring. • Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion. Possibly requires more than 1 infusion for complete resolution. • Fair: Probable and/or slight relief of pain and slight improvement in signs of bleeding after single infusion. Required more than 1 infusion for complete resolution. • None: No improvement or condition worsens.
  • Development of, and changes to, the titer of inhibitory and binding antibodies to recombinant porcine factor VIII (rpFVIII) [ Time Frame: ≤45 days prior to Day 0; postoperative day 14 or discharge (whichever is earlier); optional testing between day 7- 14 after discharge; and day 42 after discharge ]
  • Development of, and changes to, the titer of inhibitory and binding antibodies to human factor VIII (hFVIII) [ Time Frame: ≤45 days prior to Day 0; postoperative day 14 or discharge (whichever is earlier); optional testing between day 7- 14 after discharge; and day 42 after discharge ]
  • Development of binding antibodies to baby hamster kidney (BHK) proteins [ Time Frame: ≤45 days prior to Day 0; postoperative day 14 or discharge (whichever is earlier); optional testing between day 7- 14 after discharge; and day 42 after discharge ]
  • Occurrence of thrombotic events [ Time Frame: After signing informed consent until day 42 after discharge (end of study visit) ]
  • Incidence of severe allergic reactions (eg, anaphylaxis) [ Time Frame: From Day 0 (day of surgery) through Day 42 post-surgery (End of Study Visit) ]
  • Incidence of other investigational product (IP)-related adverse events (AEs) [ Time Frame: From Day 0 (day of surgery) through Day 42 post-surgery (End of Study Visit) ]
  • Incidence of clinically significant changes in vital signs [ Time Frame: Within 30 minutes pre, and 30 minutes post-dose ]
  • Incidence of clinically significant changes in routine laboratory parameters - hematology labs [ Time Frame: Up to 45 days prior to Day 0 (day of surgery) through Day 42 post-surgery (End of Study Visit) ]
  • Incidence of clinically significant changes in routine laboratory parameters - clinical chemistry [ Time Frame: Up to 45 days prior to Day 0 (day of surgery) through Day 42 post-surgery (End of Study Visit) ]
  • Daily administration of BAX 802 per participant [ Time Frame: Day 0 (day of surgery) thru Day 14 or discharge (whichever is earlier) ]
  • Total weight-adjusted administration of BAX 802 per participant [ Time Frame: Day 0 (day of surgery) thru Day 14 or discharge (whichever is earlier) ]
  • Volume (mL) of Blood Products Transfused. [ Time Frame: From initiation of the surgery until Day 14 or discharge (whichever is earlier) ]
    Volume of blood transfused may include: blood, red blood cells, platelets, and other blood products transfused
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE BAX 802 in CHA With Inhibitors
Official Title  ICMJE A Phase 3, Multicenter, Open-label Study of the Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (BAX 802) in Subjects With Congenital Hemophilia A With Factor VIII Inhibitors Undergoing Surgical or Other Invasive Procedures
Brief Summary The purpose of this study is to evaluate the efficacy and safety of BAX 802 in males with congenital hemophilia A (CHA) with inhibitors who are undergoing major or minor elective surgical, dental, or other invasive procedures.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hemophilia A
Intervention  ICMJE Biological: Antihemophilic Factor (Recombinant), Porcine Sequence (BAX802)
In case of major surgery, FVIII target level is ≥80% for major surgeries/ procedures and ≥50% for minor surgeries/ procedures.
Other Names:
  • BAX 802
  • BAX802
  • recombinant porcine factor VIII
  • Obizur
  • rpFVIII
Study Arms  ICMJE Experimental: BAX802 in Surgery
Participants who are undergoing major or minor elective surgical, dental, or other invasive procedures.
Intervention: Biological: Antihemophilic Factor (Recombinant), Porcine Sequence (BAX802)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 6, 2016)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 16, 2021
Estimated Primary Completion Date April 2, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria

  1. Participant requires a major or minor elective surgical, dental or other invasive procedure
  2. Participant is male and ≥ 12 to ≤ 75 years old at the time of screening
  3. Participant has provided signed informed consent (and assent for adolescent participants, as applicable) in accordance with local regulatory requirements
  4. Participant has severe (factor VIII (FVIII) level < 1%) or moderately severe (FVIII level ≤ 2%) congenital hemophilia A (CHA) with inhibitors to human factor VIII (hFVIII) of ≥ 0.6 Bethesda units (BU), as tested at screening at the central laboratory
  5. Participant is not currently receiving or has recently received (< 30 days) immune tolerance induction (ITI) therapy
  6. Participant has a Karnofsky performance score of ≥ 60 at screening
  7. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3 at screening
  8. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing; or HCV+ with chronic stable hepatitis disease. Positive serologies will be confirmed by PCR testing.
  9. Participant is willing and able to comply with the requirements of the protocol.

Exclusion Criteria

  1. The participant requires emergency surgery
  2. Severe chronic liver dysfunction or disease (e.g., ≥ 5 × upper limit of normal [ULN] alanine aminotransferase [ALT], as confirmed by central laboratory at screening or a documented prothrombin time/international normalized ratio [PT/INR] > 1.5)
  3. Clinically symptomatic renal disease (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening
  4. Anti-porcine factor VIII (pFVIII) inhibitor > 10 BU prior to surgery
  5. Platelet count < 100,000/μL at screening
  6. Participant has another active coagulation disorder, other than hemophilia A, as per the medical history
  7. Planned use of α-interferon with or without ribavirin for HCV infected patients or planned use of a protease inhibitor for HIV infected patients. Patients currently taking any of these medications for ≥ 30 days are eligible
  8. Known hypersensitivity to recombinant porcine factor VIII (rpFVIII), or hamster or murine proteins
  9. Participant has an ongoing or recent (within 3 months of screening) thrombo-embolic disease, fibrinolysis or disseminated intravascular coagulation (DIC)
  10. Participant has been exposed to an IP within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study
  11. Participant is unable to tolerate quantity of blood to be drawn for protocol procedures
  12. Participant is a family member or employee of the Investigator.
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michael Krammer, MSc +43 1 20100 247 1372 michael.krammer@shire.com
Contact: Shire Contact +1 866 842 5335 ClinicalTransparency@shire.com
Listed Location Countries  ICMJE Canada,   Germany,   Italy,   Netherlands,   Poland,   South Africa,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02895945
Other Study ID Numbers  ICMJE 241502
2015-005521-39 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Shire ( Baxalta now part of Shire )
Study Sponsor  ICMJE Baxalta now part of Shire
Collaborators  ICMJE Baxalta Innovations GmbH, now part of Shire
Investigators  ICMJE
Study Director: Study Director Shire
PRS Account Shire
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP