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

NCT ID: NCT01178294

Last Updated: 2021-05-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-11-10
• Study Completion Date: 2013-10-09

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.

Conditions

Acquired Hemophilia A

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

OBI-1

Intervention Type: BIOLOGICAL

Intravenous infusion

Interventions

OBI-1

Intravenous infusion

Intervention Type: BIOLOGICAL

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Baxalta now part of Shire

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, United States

Louisiana Center for Bleeding & Clotting Disorders

New Orleans, Louisiana, United States

National Institutes of Health - Warren G. Magnuson Clinical Center

Bethesda, Maryland, United States

Tufts Medical Center

Boston, Massachusetts, United States

Brigham and Women's Hospital

Boston, Massachusetts, United States

University of North Carolina at Chapel Hill Hospital

Chapel Hill, North Carolina, United States

The Pennsylvania State University and Milton S. Hershey Medical Center

Hershey, Pennsylvania, United States

Vanderbilt University Medical Center, Hemostasis/Hemophilia Clinic

Nashville, Tennessee, United States

Maisonneuve-Rosemont Hospital

Montreal, Quebec, Canada

Apollo Hospitals

Chennai, Tamil Nadu, India

Royal Free Hospital-Katharine Dormandy Haemophilia Centre and Thrombosis Unit

London, England, United Kingdom

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, Hampshire/England, United Kingdom

Countries

United States; Canada; India; United Kingdom

References

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.

Reference Type: RESULT

PMID: 25623166 (View on PubMed)

Miesbach W, Curry N, Knobl P, Percy C, Santoro R, Schmaier AH, Trautmann-Grill K, Badejo K, Chen J, Nouri M, Oberai P, Klamroth R. Real-world use of recombinant porcine sequence factor VIII in the treatment of acquired hemophilia A: EU PASS. Ther Adv Hematol. 2024 Sep 2;15:20406207241260332. doi: 10.1177/20406207241260332. eCollection 2024.

Reference Type: DERIVED

PMID: 39228858 (View on PubMed)

Other Identifiers

OBI-1-301

Identifier Type: -

Identifier Source: org_study_id