Clinical trial NCT01178294: Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Acquired Hemophilia A
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Acquired Hemophilia A
Keywords: haemophilia A
blood coagulation disorders
coagulation protein disorder
hemophilia A
Acquired Hemophilia A
hematologic diseases
hemorrhagic disorders
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-08-10
Enrollment: 29
Sex: ALL
Minimum age (years): 18
Standard ages: 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 acquired hemophilia A.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Serious Bleeding Episodes Responsive to OBI-1
timeFrame: 24 hours after initiation of treatment
Secondary outcomes:
measure: Overall Percentage of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator
timeFrame: At the time of final treatment dosing (varied from participant to participant depending on bleeding episodes)
measure: 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
timeFrame: 8 hours
measure: 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
timeFrame: 16 hours
measure: Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes
timeFrame: Time of successful control of qualifying bleeding episode (varied from participant to participant)
measure: Total Dose of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes
timeFrame: Time of successful control of qualifying bleeding episode (varied from participant to participant)
measure: Total Number of Infusions of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes
timeFrame: Time of successful control of qualifying bleeding episode (varied from participant to participant)
measure: Correlation Between Positive Response to OBI-1 Therapy at 8 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours
timeFrame: 24 hours
measure: Correlation Between Response to OBI-1 Therapy at 16 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours
timeFrame: 24 hours
measure: Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes at 24 Hours
timeFrame: 24 hours
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: Through 90 days ± 7 days following final OBI-1 dose
measure: Pharmacokinetics (PK) Analysis- Plasma Clearance
timeFrame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours
measure: PK Analysis- Volume of Distribution (Vd) at Steady State
timeFrame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours
measure: PK Analysis- Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Measurable Concentration
timeFrame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours
measure: PK Analysis- Terminal Half-life
timeFrame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours
measure: Number of Participants Who Developed de Novo Anti-OBI-1 Antibody Titers
timeFrame: Through 90 days ± 7 days following final OBI-1 dose
measure: Number of Participants Who Developed an Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer
timeFrame: Through 90 days ± 7 days following final OBI-1 dose
Other outcomes:
measure: Anti-human Factor VIII Antibody Titer
timeFrame: Through 90 days ± 7 days following final OBI-1 dose
Locations:
city: Indianapolis
country: United States
facility: Indiana Hemophilia and Thrombosis Center
state: Indiana
city: New Orleans
country: United States
facility: Louisiana Center for Bleeding & Clotting Disorders
state: Louisiana
city: Bethesda
country: United States
facility: National Institutes of Health - Warren G. Magnuson Clinical Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill Hospital
state: North Carolina
city: Hershey
country: United States
facility: The Pennsylvania State University and Milton S. Hershey Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University Medical Center, Hemostasis/Hemophilia Clinic
state: Tennessee
city: Montreal
country: Canada
facility: Maisonneuve-Rosemont Hospital
state: Quebec
city: Chennai
country: India
facility: Apollo Hospitals
state: Tamil Nadu
city: London
country: United Kingdom
facility: Royal Free Hospital-Katharine Dormandy Haemophilia Centre and Thrombosis Unit
state: England
city: Basingstoke
country: United Kingdom
facility: Basingstoke and North Hampshire NHS Foundation Trust
state: Hampshire/England
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: 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):162-170. doi: 10.1111/hae.12627. Epub 2015 Jan 27.