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

NCT01178294 | Completed Phase 2 Results DMC

• 1 other identifier: OBI-1-301
• Study Type: interventional
• Target: 29
• Locations: 4 countries
• Sites: 12

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

Keywords

haemophilia A; blood coagulation disorders; coagulation protein disorder; hemophilia A; Acquired Hemophilia A; hematologic diseases; hemorrhagic disorders

Outcome Measures

Primary Outcomes (1)

• Percentage of Serious Bleeding Episodes Responsive to OBI-1

  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%'.

  24 hours after initiation of treatment

Secondary Outcomes (16)

• Overall Percentage of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator

  At the time of final treatment dosing (varied from participant to participant depending on bleeding episodes)

• 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

  8 hours

• 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

  16 hours

• Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes

  Time of successful control of qualifying bleeding episode (varied from participant to participant)

• Total Dose of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes

  Time of successful control of qualifying bleeding episode (varied from participant to participant)

Other Outcomes (1)

• Anti-human Factor VIII Antibody Titer

  Through 90 days ± 7 days following final OBI-1 dose

Study Arms (1)

OBI-1

EXPERIMENTAL

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)

Biological: OBI-1

Interventions

OBI-1 BIOLOGICAL

Intravenous infusion

OBI-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Baxalta now part of Shire: lead

Study Sites (12)

Indiana Hemophilia and Thrombosis Center

Indianapolis, Indiana, 46260, United States

Location

Louisiana Center for Bleeding & Clotting Disorders

New Orleans, Louisiana, 70112-2699, United States

Location

National Institutes of Health - Warren G. Magnuson Clinical Center

Bethesda, Maryland, 20892-1508, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

University of North Carolina at Chapel Hill Hospital

Chapel Hill, North Carolina, 27599-7305, United States

Location

The Pennsylvania State University and Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Vanderbilt University Medical Center, Hemostasis/Hemophilia Clinic

Nashville, Tennessee, 37232-9830, United States

Location

Maisonneuve-Rosemont Hospital

Montreal, Quebec, H1T 2M4, Canada

Location

Apollo Hospitals

Chennai, Tamil Nadu, 600006, India

Location

Royal Free Hospital-Katharine Dormandy Haemophilia Centre and Thrombosis Unit

London, England, NW3 2QG, United Kingdom

Location

Basingstoke and North Hampshire NHS Foundation Trust

Basingstoke, Hampshire/England, RG249NA, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 25623166 RESULT

• 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.

  PMID: 39228858 DERIVED

MeSH Terms

Conditions

Factor 8 deficiency, acquired; Hemophilia A; Blood Coagulation Disorders; Coagulation Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Limitations and Caveats

Due to the low number of subjects available for evaluation, statistical tests could only be performed for the primary outcome measure. The results of all other outcome measures are descriptive.

Results Point of Contact

• Title: Study Director
• Organization: Shire

ClinicalTransparency@shire.com

+1 866 842 5335

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2010
• First Posted: August 10, 2010
• Study Start: November 10, 2010
• Primary Completion: July 1, 2013
• Study Completion: October 9, 2013
• Last Updated: May 13, 2021
• Results First Posted: December 21, 2015

Record last verified: 2021-04

Locations

CA (1); IN (1); US (8); GB (2)