Hemophilia Inhibitor Clinical Trials (INHIBIT) Platform

This is a multi-center, randomized Phase III Clinical Trials Platform (INHIBIT) in which hemostatic agents will be compared using adaptive design to prevent and eradicate inhibitors in patients with severe hemophilia A. This adaptive design is necessary as randomized trials in rare diseases are otherwise not possible. The INHIBIT Trial Platform includes one Inhibitor Prevention Trial and one Inhibitor Eradication Trial that will be conducted at up to 41 U.S. hemophilia treatment centers (HTCs) affiliated with universities. The Inhibitor Prevention Trial is a 48-week randomized phase III trial in which 66 previously untreated patients (PUPs) (children \< 6 yr) with severe hemophilia A will be enrolled and randomized to preemptive weekly Eloctate vs. Emicizumab to prevent inhibitor formation, defined as anti-FVIII \> 5.0 BU. The Inhibitor Eradication Trial is a 48-week randomized phase III trial in which 90 previously-treated patients (PTPs) with severe hemophilia A and high-responding inhibitors (anti-VIII \>5.0 B.U.), including subjects developing inhibitors during the Prevention Trials and adults or children of any age at the same HTCs refractory to or never previously tolerated, will be enrolled and randomized to Eloctate ITI god plus weekly Emicizumab vs. Eloctate ITI alone to eradicate inhibitor formation, defined as anti-FVIII\<0.6 B.U. Blood draws will be minimized to 6 timepoints, pre, 4, 12, 24, 36, and 48 weeks, and validated for small volumes, 3.8 cc (¾ tsp) each. The Inhibit Trials Platform is considered greater than minimal risk as study drug is given before the first bleed and special inhibitor studies are obtained.