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

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ClinicalTrials.gov Identifier: NCT01178294
Recruitment Status : Completed
First Posted : August 10, 2010
Results First Posted : December 21, 2015
Last Update Posted : May 13, 2021
Sponsor:
Information provided by (Responsible Party):
Takeda ( Baxalta now part of Shire )

Tracking Information
First Submitted Date  ICMJE August 6, 2010
First Posted Date  ICMJE August 10, 2010
Results First Submitted Date  ICMJE April 28, 2015
Results First Posted Date  ICMJE December 21, 2015
Last Update Posted Date May 13, 2021
Actual Study Start Date  ICMJE November 10, 2010
Actual Primary Completion Date July 1, 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 17, 2015)
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 Measures  ICMJE
 (submitted: August 9, 2010)
Proportion of serious bleeding episodes responsive to OBI-1 [ Time Frame: 24 hours after initiation of treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2015)
  • 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 15-20 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. AUC was calculated as area under the percent activity-time curve.
  • PK Analysis- Terminal Half-life [ 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. Half-life was calculated as the time it took to reduce percent activity by half.
  • Number of Participants Who Developed de Novo Anti-OBI-1 Antibody Titers [ Time Frame: Through 90 days ± 7 days following final OBI-1 dose ]
  • Number of Participants Who Developed an Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer [ Time Frame: Through 90 days ± 7 days following final OBI-1 dose ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: November 17, 2015)
Anti-human Factor VIII Antibody Titer [ Time Frame: Through 90 days ± 7 days following final OBI-1 dose ]
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Acquired Hemophilia A
Official Title  ICMJE 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 Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acquired Hemophilia A
Intervention  ICMJE Biological: OBI-1
Intravenous infusion
Study Arms  ICMJE Experimental: OBI-1
Initial dose: 200 U/kg - additional doses at the discretion of the investigator based on FVIII activity level and clinical assessment of response to treatment (upper limit: 400 U/kg every 2 hours)
Intervention: Biological: OBI-1
Publications * Kruse-Jarres R, St-Louis J, Greist A, Shapiro A, Smith H, Chowdary P, Drebes A, Gomperts E, Bourgeois C, Mo M, Novack A, Farin H, Ewenstein B. Efficacy and safety of OBI-1, an antihaemophilic factor VIII (recombinant), porcine sequence, in subjects with acquired haemophilia A. Haemophilia. 2015 Mar;21(2):162-70. doi: 10.1111/hae.12627. Epub 2015 Jan 27.

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: November 17, 2015)
29
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2010)
28
Actual Study Completion Date  ICMJE October 9, 2013
Actual Primary Completion Date July 1, 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent from subject, trusted person or person who is legally authorized to sign on behalf of the participant (Legal Representative in U.S.), depending on local regulations
  • Participants with acquired hemophilia with autoimmune inhibitory antibodies to human factor VIII with a clinical diagnosis established by the following criteria: a) Prolonged activated partial thromboplastin time (aPTT), b) Prothrombin time (PT) ≤ upper limit of normal (ULN) + 2 seconds and platelet count within normal range, c) Abnormal aPTT mixing study (patient-normal control 1:1) consistent with a factor VIII inhibitors reduced factor VIII activity level (below 10%)
  • Has a serious bleeding episode, as documented by the investigator
  • Be willing and able to follow all instructions and attend all study visits
  • Participants taking anti-thrombotics (such as clopidogrel, heparin or heparin analogue) may be included provided three half-lives of the agent have elapsed since the last dose of the agent
  • Life expectancy, prior to onset of the hemorrhagic episode, of at least 90 days
  • Participants of reproductive age must use acceptable methods of contraception and if female, undergo pregnancy testing as part of the screening process

Exclusion Criteria:

  • Hemodynamically unstable after blood transfusion, fluid resuscitation and pharmacologic or volume replacement pressor therapy. This hemodynamic instability is characterized by symptomatic hypotension resulting in vital organ dysfunction, such as cardiac ischemia, oliguria (urine volume <0.5 mL/kg in the previous six hours), central nervous system hypoperfusion manifested by mental status change such as confusion (unless head injury or intracranial hemorrhage is present), pulmonary compromise, and/or acidosis (manifested by pH and lactate levels)
  • Has an established reason for bleeding that is not correctable
  • Bleeding episode assessed likely to resolve on its own if left untreated
  • Anti-OBI-1 inhibitor that exceeds 20 Bethesda Units (BU) (prospectively or retrospectively)
  • Subsequent bleeding episode at the site of the initial qualifying bleeding episode within two weeks following the final OBI-1 dose for the initial qualifying bleeding episode, or subsequent bleeding episode at a different site than the initial qualifying bleeding episode within 1 week following the final OBI-1 dose for the initial qualifying bleeding episode will not be considered "new" qualifying bleeding episodes
  • Prior history of bleeding disorder other than acquired hemophilia.
  • Known major sensitivity to therapeutic products of pig or hamster origin; examples include therapeutics of porcine origin (e.g. previously marketed porcine factor VIII, Hyate-C®) and recombinant therapeutics prepared from hamster cells (e.g. Humira®, Advate® and Enbrel®)
  • Use of hemophilia medication: rFVIIa within 3 hours prior to OBI-1 administration or aPCC treatment within 6 hours prior to OBI-1 administration
  • Participation in any other clinical study within 30 days of the first OBI-1 treatment
  • Anticipated need for treatment or device during the study that may interfere with the evaluation of the safety or efficacy of OBI-1, or whose safety or efficacy may be affected by OBI-1
  • Is currently pregnant, breastfeeding, or planning to become pregnant or father a child during the study
  • Abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the subject's safety or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study
  • Inability or unwillingness to comply with the study design, protocol requirements, or the follow-up procedures
  • Participant of majority age under legal protection
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   India,   United Kingdom,   United States
Removed Location Countries France,   Germany,   Hungary,   Italy,   Sweden
 
Administrative Information
NCT Number  ICMJE NCT01178294
Other Study ID Numbers  ICMJE OBI-1-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Takeda ( Baxalta now part of Shire )
Study Sponsor  ICMJE Baxalta now part of Shire
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Study Director Takeda
PRS Account Takeda
Verification Date April 2021

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