Clinical trial NCT01434511: Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Congenital Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: hemophilia A
haemophilia A
blood coagulation disorders
hemorrhagic disorders
coagulation protein disorder
hematologic diseases
congenital hemophilia A
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2011-09-15
Enrollment: 1
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 congenital hemophilia A.


Eligibility 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.

Primary outcomes:
measure: Proportion of Serious Bleeding Episodes Responsive to OBI-1
timeFrame: 24 hours after initiation of treatment
Secondary outcomes:
measure: Overall Proportion of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Proportion of Bleeding Episodes Responsive to OBI-1 Therapy at Designated Assessment Time Points After the Initiation of Therapy, as Assessed by the Investigator
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Total Dose of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Total Number of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: 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.
timeFrame: Frame: Through 90 days ± 7days following final OBI-1 dose
measure: Correlation Between the Pre-infusion Anti-OBI-1 Antibody Titers and the Recovery of OBI-1.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Recovery and Elimination Rate Parameters of OBI-1 in Subjects With Inhibitors Treated With OBI-1 Therapy.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Efficacy Assessment of OBI-1 in Participants With Anti-human Factor VIII Titers >30 Bethesda Units (BU)
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Anti-human Factor VIII Antibody Titer.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Anti-OBI-1 Antibody Titer.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
measure: Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer.
timeFrame: Through 90 days ± 7days following final OBI-1 dose
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: Johannesburg
country: South Africa
facility: Charlotte Maxeke Johannesburg Academic Hospital
state: Gauteng
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
state: England
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: