Clinical Trial: Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Acquired Hemophilia A

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (OBI-1) in the Treatment of Acquired Hemophilia A Due to Factor VIII Inhibitory Auto-antibodies

Brief Summary: This study is to test whether the study drug (OBI-1) is safe and effective for the treatment of serious bleeding episodes in people with acquired hemophilia A.

Detailed Summary:
Sponsor: Baxalta US Inc.

Current Primary Outcome: Percentage of Serious Bleeding Episodes Responsive to OBI-1 [ Time Frame: 24 hours after initiation of treatment ]

The initial serious ("qualifying") bleeding episode for each subject was analyzed for the primary efficacy outcome measure. A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.


Original Primary Outcome: Proportion of serious bleeding episodes responsive to OBI-1 [ Time Frame: 24 hours after initiation of treatment ]

Current Secondary Outcome:

  • Overall Percentage of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator [ Time Frame: At the time of final treatment dosing (varied from participant to participant depending on bleeding episodes) ]
    Treatment success was defined as control of qualifying bleeding episode at the time of final treatment dosing. A serious bleeding episode was considered 'successfully controlled' if the investigator had checked 'completed OBI-1 therapy as treatment success' on the eCRF.
  • Percentage of Serious Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator [ Time Frame: 8 hours ]
    A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.
  • Percentage of Serious Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator [ Time Frame: 16 hours ]
    A 'positive response' is defined as 'effective' (bleeding stopped with clinical control and FVIII levels of 50% or higher ) or 'partially effective' (bleeding reduced with clinical stabilization and FVIII levels of 20% or higher) control of bleeding, as determined by the investigator using a 4-point rating scale (effective - partially effective - poorly effective - not effective). 'Poorly effective' is defined as 'bleeding slightly reduced or unchanged and FVIII levels of less than 50%'. 'Not effective' is defined as 'bleeding worsening and FVIII levels of less than 50%'.
  • Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes [ Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant) ]
    'Frequency of infusions' was calculated as the 'average number of infusions per day'. 'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'.
  • Total Dose of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes [ Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant) ]
    'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'.
  • Total Number of Infusions of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes [ Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant) ]
    'Qualifying bleeding episode' was defined as the 'initial, serious bleeding episode'. A serious bleeding episode was considered 'successfully controlled' if the investigator had checked 'completed OBI-1 therapy as treatment success' on the eCRF.
  • Correlation Between Positive Response to OBI-1 Therapy at 8 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours [ Time Frame: 24 hours ]
  • Correlation Between Response to OBI-1 Therapy at 16 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours [ Time Frame: 24 hours ]
  • Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes at 24 Hours [ Time Frame: 24 hours ]
  • Correlation Between the Pre-infusion Anti-OBI-1 Antibody Titers, the Total Dose of OBI-1, the Outcome at 24 Hours and the Eventual Control of the Bleeding Episode [ Time Frame: Through 90 days ± 7 days following final OBI-1 dose ]
  • Pharmacokinetics (PK) Analysis- Plasma Clearance [ Time Frame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours ]
    Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics.
  • PK Analysis- Volume of Distribution (Vd) at Steady State [ Time Frame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours ]
    Participation in the PK sampling was optional. PK parameters obtained from the non-bleeding state were summarized with descriptive statistics.
  • PK Analysis- Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Measurable Concentration [ Time Frame: Pre-infusion 15

    Original Secondary Outcome:

    Information By: Baxalta US Inc.

    Dates:
    Date Received: August 6, 2010
    Date Started: November 2010
    Date Completion:
    Last Updated: November 17, 2015
    Last Verified: November 2015