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

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
Baxter Healthcare Corporation
ClinicalTrials.gov Identifier:
NCT01434511
First received: September 13, 2011
Last updated: September 27, 2013
Last verified: September 2013
  Purpose

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 congenital hemophilia A.


Condition Intervention Phase
Hemophilia A
Biological: OBI-1
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of B-Domain Deleted Recombinant Porcine Factor VIII (OBI-1) in the Treatment of Patients With Congenital Hemophilia A With Factor VIII Inhibitors

Resource links provided by NLM:


Further study details as provided by Baxter Healthcare Corporation:

Primary Outcome Measures:
  • Proportion of serious bleeding episodes responsive to OBI-1 [ Time Frame: 24 hours after initiation of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Overall proportion of serious bleeding episodes successfully controlled with OBI-1 therapy, as assessed by the investigator. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Proportion of bleeding episodes responsive to OBI-1 therapy at designated assessment time points after the initiation of therapy, as assessed by the investigator [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Frequency of infusions of OBI-1 required to successfully control qualifying bleeding episodes. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Total dose of OBI-1 required to successfully control qualifying bleeding episodes. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Total number of infusions of OBI-1 required to successfully control qualifying bleeding episodes. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Correlation between response to OBI-1 therapy at specified time points and eventual control of serious bleeding episodes. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • 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: Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Correlation between the pre-infusion anti-OBI-1 antibody titers and the recovery of OBI-1. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Recovery and elimination rate parameters of OBI-1 in subjects with inhibitors treated with OBI-1 therapy. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Efficacy assessment of OBI-1 in participants with anti-human factor VIII titers >30 Bethesda Units (BU) [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: No ]
  • Anti-human factor VIII antibody titer. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: Yes ]
  • Anti-OBI-1 antibody titer. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: Yes ]
  • Anti-host cell protein baby hamster kidney (BHK) antibody titer. [ Time Frame: Through 90 days ± 7days following final OBI-1 dose ] [ Designated as safety issue: Yes ]

Enrollment: 1
Study Start Date: August 2011
Estimated Study Completion Date: July 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OBI-1 Biological: OBI-1
intravenous infusion, up to every 2-3 hours for the first 24 hours of treatment

  Eligibility

Ages Eligible for Study:   6 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Written informed consent/assent from participant and/or participant's parent or legal representative.
  • Participants with congenital hemophilia A with human factor VIII inhibitor ≤30 BU assessed within 90 days prior to study entry.
  • Has previously or is currently demonstrating suboptimal hemostatic response to bypassing agents for treatment of bleeding episodes; suboptimal response is determined by the investigator , but minimally includes no or minimal evidence of response after at least two doses of bypassing agents, either for the current or a historic bleeding episode.
  • Has an anti-OBI-1 titer ≤ 10 BU
  • Has any serious or life-threatening bleeding episode; or requires a surgical procedure that could lead to a serious bleeding episode if not well controlled.
  • Is willing and able to follow all instructions and attend all study visits.
  • Has no other significant hemostatic abnormality and:

    • Platelets ≥100,000/mm-cubed
    • Prothrombin time < 15 seconds
    • INR < 1.3
  • 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.

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).
  • Bleeding episode assessed likely to resolve on its own if left untreated.
  • Use of hemophilia medication: recombinant factor VIIa within 3 hours prior to OBI-1 administration or activated prothrombin complex concentrate (aPCC) treatment within 6 hours prior to OBI-1 administration
  • Prior history of bleeding disorder other than congenital hemophilia A
  • Known major sensitivity (anaphylactoid reactions) to porcine or hamster products. 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®).
  • Received any other investigational treatment 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 planning to father a child during the study
  • Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardize the participant'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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434511

Locations
United States, Indiana
Indiana Hemophilia and Thrombosis Center
Indianapolis, Indiana, United States, 46260
South Africa
Charlotte Maxeke Johannesburg Academic Hospital
Johannesburg, Gauteng, South Africa, 2193
United Kingdom
Great Ormond Street Hospital
London, England, United Kingdom, WC1N 3JH
Sponsors and Collaborators
Baxter Healthcare Corporation
Investigators
Study Director: Heinrich Farin, MD Baxter Healthcare Corporation
  More Information

No publications provided

Responsible Party: Baxter Healthcare Corporation
ClinicalTrials.gov Identifier: NCT01434511     History of Changes
Other Study ID Numbers: OBI-1-302
Study First Received: September 13, 2011
Last Updated: September 27, 2013
Health Authority: United States: Food and Drug Administration
South Africa: Medicines Control Council
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Baxter Healthcare Corporation:
hemophilia A
haemophilia A
blood coagulation disorders
hemorrhagic disorders
coagulation protein disorder
hematologic diseases
congenital hemophilia A

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
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014