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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01178294
• Date of registration: 06/08/2010
• Prospective Registration: Yes
• Primary sponsor: Baxalta now part of Shire
• Public title: Study of Modified Recombinant Factor VIII (OBI-1) in Subjects With Acquired Hemophilia A
• Scientific 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
• Date of first enrolment: November 10, 2010
• Target sample size: 29
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01178294
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

Canada, France, Germany, Hungary, India, Italy, Sweden, United Kingdom, United States

Contacts

• Name: Study Director
• Affiliation: Shire

Key inclusion & exclusion 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Acquired Hemophilia A

Intervention(s)

Biological: OBI-1

Primary Outcome(s)

Percentage of Serious Bleeding Episodes Responsive to OBI-1 [Time Frame: 24 hours after initiation of treatment]

Secondary Outcome(s)

Number of Participants Who Developed de Novo Anti-OBI-1 Antibody Titers [Time Frame: Through 90 days ± 7 days following final OBI-1 dose]

Overall Percentage of Serious Bleeding Episodes Successfully Controlled With OBI-1 Therapy, as Assessed by the Investigator [Time Frame: At the time of final treatment dosing (varied from participant to participant depending on bleeding episodes)]

Correlation Between Response to OBI-1 Therapy at Specified Time Points and Eventual Control of Serious Bleeding Episodes at 24 Hours [Time Frame: 24 hours]

PK Analysis- Volume of Distribution (Vd) at Steady State [Time Frame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

Number of Participants Who Developed an Anti-host Cell Protein Baby Hamster Kidney (BHK) Antibody Titer [Time Frame: Through 90 days ± 7 days following final OBI-1 dose]

Total Dose of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes [Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant)]

Correlation Between Positive Response to OBI-1 Therapy at 8 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours [Time Frame: 24 hours]

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

Correlation Between Response to OBI-1 Therapy at 16 Hours and Eventual Control of Serious Bleeding Episodes at 24 Hours [Time Frame: 24 hours]

Frequency of Infusions of OBI-1 Required to Successfully Control Qualifying Bleeding Episodes [Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant)]

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 [Time Frame: 8 hours]

PK Analysis- Area Under the Concentration-time Curve (AUC) From Time 0 to the Last Measurable Concentration [Time Frame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

Total Number of Infusions of OBI-1 Required to Successfully Control 'Qualifying' Bleeding Episodes [Time Frame: Time of successful control of qualifying bleeding episode (varied from participant to participant)]

Pharmacokinetics (PK) Analysis- Plasma Clearance [Time Frame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 hours]

PK Analysis- Terminal Half-life [Time Frame: Pre-infusion 15-20 minutes, Post-infusion 1, 3, 6, 12, 18, 24 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 [Time Frame: 16 hours]

Secondary ID(s)

OBI-1-301

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 21/12/2015
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01178294