Two clinical trials launching in December will use Octapharma USA’s Wilate, von Willebrand Factor/Coagulation Factor VIII Complex (Human) Lyophilized Powder for Solution for Intravenous Injection, in patients with hemophilia A.
Hemophilia A is an X-linked hereditary bleeding disorder that results from either reduced or absent levels of coagulation factor VIII (FVIII). One of the biggest challenges in the management of hemophilia is the development of inhibitors, an immune response to treatment with clotting factor concentrates that reduces the effectiveness of the factors and makes it more difficult to stop bleeding episodes, resulting in an increase in morbidity and resource utilization.
Immune tolerance induction (ITI), which involves the daily infusion of large doses of FVIII over many months and the use of immunosuppressive agents and other procedures, is used to eradicate the inhibitor and normalize drug parameters, so that patients can then be treated with human FVIII concentrates.
INITIATE (Individualized ITI Based on FVIII Protection by VWF) is a major multicenter clinical trial funded by Octapharma, that will investigate the potential of individualized immune tolerance induction (ITI) therapy to reduce the time it takes to eradicate inhibitors in hemophilia A treatment. The study titled “Individualized ITI Based on FVIII Protection by VWF (INITIATE),” will be co-led by Jonathan Ducore, MD, of the University of California Davis School of Medicine and Courtney Thornburg, MD, of the Rady Children’s Hospital-San Diego.
In one of the study arms, patients’ plasma will be analyzed against different lots of the company’s von Willebrand factor-coagulation factor VIII complex (human) (Wilate) in vitro prior to treatment initiation to determine the lot with the highest residual factor VIII activity left after incubation with patients’ plasma.
“Anti-FVIII inhibitor formation is the most serious complication of hemophilia A treatment today, occurring in up to 20 to 30 percent, or more, of those with severe hemophilia A,” Ducore said in a press release. “Use of FVIII is generally futile in this group, because the inhibitor will rapidly inactivate the infused concentrate. ITI can result in inhibitor resolution, but can take several years to achieve success. Preliminary studies have suggested that individualized lot selection (batch-matching) can shorten this time by 67 percent,” Ducore said.
The study will compare the time to inhibitor with the plasma-derived von Willebrand factor (VWF)/coagulation factor (FVIII) complex concentrate in patients with congenital hemophilia A, FVIII activity of or less than 2%, and a historical high-titer inhibitor [equal or more than 5 Bethesda Unit (BU), a measure of blood coagulation inhibitor activity].
Up to 120 patients will be randomly assigned to either this individualized lot selection or random lot selection, the currently standard practice in the United States for ITI. The primary endpoint is the time to inhibitor titer <0.6 BU, which is postulated to correlate with a reduction in bleeding rates, morbidity, care costs and better quality of life.
A second international, multicentre Phase 3 clinical trial (NCT02954575) will examine the efficacy, safety, properties, and effect on the immune system of Wilate in up to 55 previously treated patients with severe hemophilia A. The trial will be conducted at multi clinical centers across the United States and Europe. The primary endpoint is the reduction of total annualized bleeding rate at six months. The trial is not yet recruiting participants.