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

NCT04205175 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: 19 00367
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemophilia A With Inhibitor

Outcome Measures

Primary Outcomes (1)

• Thrombin generation

  Thrombin generation capacity of the patients will be measured after every Feiba infusion with Thrombin Generation Assay.

  The goal is to complete all study procedures within 12 months.

Interventions

Feiba DRUG

This is a single center, open label, dose escalation study of in vivo administration of Feiba in congenital hemophilia A patients with inhibitors who are on emicizumab.

Eligibility Criteria

• Gender Eligibility Details: Since Hemophilia is a X-linked bleeding disorder occurring mostly in males we expected to mostly enroll male-identified subjects.
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male patients with congenital hemophilia A of any severity and any age.
• History of high titer factor VIII inhibitor (Bethesda unit \>5)
• Currently prescribed bypassing agent therapy for bleed management.
• Current treatment with emicizumab for a minimum of 2 months without interruption.

You may not qualify if:

• Active bleed requiring factor therapy at screening.
• Treatment with rFVIIa or aPCC 7 days prior to screening.
• Surgical procedure 14 days prior to screening.
• Current use of any medication other than emicizumab that could affect the coagulation system e.g. aspirin, anticoagulants, etc.

Sponsors & Collaborators

• Children's Hospital Los Angeles: lead
• Takeda: collaborator

Study Sites (1)

Childrens Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

MeSH Terms

Interventions

anti-inhibitor coagulant complex

Study Officials

• Guy Young, MD

  professor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, professor

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 19, 2019
• Study Start: July 1, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 1, 2022
• Last Updated: March 9, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)