A Study to Evaluate the Safest Dose Range for FEIBA in Hemophilia A Patients With Inhibitors on Emicizumab

• Status: Active, not recruiting
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: Male

Summary

Hemophilia A is a severe, life-long, genetic bleeding disorder characterized by a deficiency of factor VIII (FVIII), a crucial cofactor of the coagulation system. The mainstay of hemophilia treatment is factor replacement therapy with FVIII clotting factor concentrates (CFC) and these can be given episodically in response to bleeding or prophylactically to prevent bleeding. The main adverse effect of FVIII CFC is the development of neutralizing anti-drug antibodies termed inhibitors, and these render replacement therapy less effective if they are low titer inhibitors or completely ineffective if they are of the high titer variety. These so-called 'inhibitor patients' cannot rely on FVIII CFC for their treatment and are treated with other CFC called bypassing agents such as activated prothrombin complex concentrate (aPCC/Feiba). While these agents can be effective in some patients for prophylaxis, they are not as effective for bleed prevention as FVIII CFC for patients without inhibitors.Recently, emicizumab (Hemlibra, Roche), was developed and licensed for the prevention of bleeding in patients with hemophilia A with and without inhibitors. However, patients in the clinical trials for emicizumab have developed thrombotic adverse events and only patients who received doses of Feiba of >100 IU/kg/24 hours for more than 24 hours developed thrombosis.

As a result of the above data, recommendations have been to either avoid altogether in patients on emicizumab, or to be very cautious about using it to treat breakthrough bleeding. With this in mind, we propose to study the in vivo combination of Feiba in patients with inhibitors on emicizumab.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Children's Hospital Los Angeles
• Collaborator: Takeda
• Treatments: Anti-inhibitor coagulant complex; Factor VIII

Criteria

Inclusion Criteria:

1. Male patients with congenital hemophilia A of any severity and any age.

2. History of high titer factor VIII inhibitor (Bethesda unit >5)

3. Currently prescribed bypassing agent therapy for bleed management.

4. Current treatment with emicizumab for a minimum of 2 months without interruption.

Exclusion Criteria:

1. Active bleed requiring factor therapy at screening.

2. Treatment with rFVIIa or aPCC 7 days prior to screening.

3. Surgical procedure 14 days prior to screening.

4. Current use of any medication other than emicizumab that could affect the coagulation system e.g. aspirin, anticoagulants, etc.