Study of Recombinant Porcine Factor VIII (FVIII) in Hemophilia and Inhibitors to FVIII
The ability of a new recombinant porcine coagulation factor VIII, B-domain deleted (called "OBI-1"), to control the non-life- or limb-threatening bleeding episodes patients with hemophilia A commonly develop is being evaluated. Patients with congenital hemophilia A and a low-titer (<20 Bethesda units [Bu]) inhibitory antibody to OBI-1, who meet the inclusion/exclusion criteria, will receive OBI-1 to treat their soft tissue or joint bleeding episode. At least the first two treatment episodes will be performed in the controlled setting of the hemophilia center/clinic/office, where any side effects can be observed. If the patient continues to meet the inclusion/exclusion criteria, has had no serious or severe adverse reactions to OBI-1, and has been in a home care program, the investigator may permit the patient to self-administer OBI-1 at home to treat subsequent bleeding episodes. The study will continue at least until 12 or more patients have received at least 24 treatment episodes in the aggregate.
Drug: recombinant porcine coagulation factor VIII (OBI-1)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An Open-Label Study of the Hemostatic Activity, Pharmacokinetics and Safety of OBI-1 (B-Domain Deleted Recombinant Porcine FVIII), When Administered by Intravenous Injection, to Control Non-Life and Non-Limb Threatening Bleeding Episodes in Congenital Hemophilia A Patients With an Inhibitor to Human FVIII|
- The percentage of successful treatment episodes, defined as having achieved control of the bleeding episode within One Loading Dose and 8 or fewer Treatment Doses, with a dose limit of 1000 U/kg in 24 hours
- Adverse events and serious adverse events observed throughout course of study
- Pattern of inhibitory antibody response to OBI-1 following treatments
- The percentage of patients who continue to qualify because their anti-OBI-1 titer remains at 20 Bu or less
- Pharmacokinetics of OBI-1 when it is administered for treatment of a qualifying bleeding episode, in the absence of an inhibitory antibody to OBI-1
|Study Start Date:||May 2005|
|Study Completion Date:||June 2007|
The primary objective of the study is to evaluate the hemostatic activity of OBI-1 to control a bleeding episode in hemophilia A patients with inhibitors who are experiencing a non-life and/or non-limb threatening bleeding episode.
The secondary objectives of this study will be to assess the:
- safety of OBI-1,
- serial anti-OBI-1 and anti-human factor VIII (fVIII) inhibitor antibody responses following therapeutic administration of OBI-1, and
- pharmacokinetics of OBI-1 administered to control a bleeding episode.
After qualifying for the study at a Screening visit, patients will come to the investigator for treatment of a qualifying bleeding episode. After baseline blood samples are taken for inhibitor titer, a Loading Dose of OBI-1, calculated to inactivate the inhibitor, will be administered intravenously. After a blood sample is drawn to measure inhibitor titer and fVIII level, a Treatment Dose of 50 U/kg is administered. Serial blood samples will be drawn for fVIII levels for pharmacokinetics. At 6-hour intervals, additional Treatment doses, at increasing dose levels up to 150 U/kg, may be given if needed. Follow-up safety evaluations, beginning at Day 14, are scheduled; inhibitor titers against human fVIII and OBI-1 will be measured to assess continuing eligibility.
A second qualifying bleeding episode will be treated as the first, but without pharmacokinetic samples. If the patient's inhibitor titer against OBI-1 rises to > 20 Bu, further treatments with OBI-1 will be suspended until the titer decreases to 20 Bu or lower. Third and subsequent treatment episodes may be self-administered by the patient, under strict supervision of the investigator, in home care.
The study will continue until at least 12 patients have received at least 24 treatments, unless the Data Safety Monitoring Committee (DSMC) recommends a change in dosing calculations sooner.
|United States, Pennsylvania|
|Blue Bell, Pennsylvania, United States, 19422|
|Principal Investigator:||Josef N Mueksch, MD, MBA||Octagen Corporation|