Hemophilia A With Inhibitor

Phase IV multi-center, US-centric, open-label, safety study enrolling participants with Hemophilia A or B with inhibitors, 12 years of age and older, who are either on long term prophylactic treatment (e.g., emicizumab) at risk of experiencing a breakthrough bleeding event (BE), or who are not on prophylactic treatment who may need to control a BE.

The goal of this clinical trial is to learn how well Altuviiio (efanesoctacog alpha) works for Immune Tolerance Induction (ITI) while using Hemlibra (emicizumab) to prevent bleeds. Participants will be given Altuviiio for their ITI therapy and also be treated with Hemlibra as standard of care prophylaxis to prevent bleeding. The research doctor will decide how much and how often the participant will get Hemlibra. Participants will need to attend visits for checkups and tests. These visits are divided into 4 periods: 1. A screening period - 1 visit up to 8 weeks before the Treatment Period starts 2. ITI Treatment Period - 1 Baseline Visit plus Interim visits that occur every 4 weeks for up to 52 weeks. (Some of the interim visits may be done via phone) 3. Tapering Period - 5 visits at weeks 2, 4, 8, 12 and 16 4. Ongoing Monitoring Period - 4 visits at weeks 20, 30, 40 and 50

Hemophilia A is a blood coagulation disorder caused by deficient or dysfunctional clotting factor VIII (FVIII) leading to incomplete haemostasis. Patients with severe Hemophilia A are predisposed to recurrent bleeding episodes (BEs) in joints and soft tissues that culminate in debiltating arthropathy and long-term morbidity. Prophylaxis with plasma-derived or recombinant FVIII concentrates effectively restores FVIII levels in patients with Hemophilia A, and significantly reduces the risk of bleeding. A critical concern for patients receiving FVIII replacement therapy is the development of neutralising antibodies (inhibitors) against the treatment. Inhibitors develop in up to 40% of patients with severe Hemophilia A when first exposed to FVIII treatment, typically within the first 20-30 exposure days (EDs) although a residual risk remains until after 75 EDs. Inhibitors preclude the use of FVIII replacement therapy for prevention and treatment of bleeding. Eradication of inhibitors therefore remains an important objective for Hemophilia A patients with inhibitors. Immune tolerance induction (ITI) therapy is the only clinically proven strategy for inhibitor eradication, and at least one attempt should be offered to patients with inhibitors. However, while ITI is well-studied and has a 60- 80% success rate, treatment regimens can be expensive and burdensome to patients. There are limited data on the use of different dose regimen of FVIII ITI in China. The INITIATE Study was designed to observe treatment strategies in patients with hemophilia A with inhibitors, with a focus on evaluating the safety and effectiveness of different dose regimens of ITI. The INITIATE Study includes multiple groups to explore factors that may affect ITI outcomes, and to explore the effects of different treatment methods on patient ITI biomarkers (genomics, transcriptomics, proteins (antibodies).

To evaluate the time of response, sustained remission rate, and relapse rate of CD38 monoclonal antibody (Daratumumab) combined with SCT800 (rFVIII) in the treatment of hemophilia A adolescents and adults with high titer inhibitors.

The goal of this multicentre, prospective, open-label, cross-over clinical study is to determine whether individualized PK-guided dosing of emicizumab is non-inferior to conventional dosing of emicizumab in the prevention of bleeding in congenital haemophilia A patients.