Individualizing Hemophilia Bypassing Agent Therapy Utilizing Thromboelastography

Not Applicable

Withdrawn

• Conditions: Hemophilia a with Inhibitors
• Interventions: Other: Thromboelastography-Guided Treatment Regimen

• Registration Number: NCT03002480
• Lead Sponsor: Children's Hospital Los Angeles

Brief Summary

This pilot study will investigate the use of thromboelastograph (TEG) to determine the primary bypassing agent for the management of bleeding in children and adults severe hemophilia A patients with inhibitors.

The study will evaluate the TEG profile for each of the available bypassing agents (FEIBA and rFVIIa) in each participating patient, which will then determine which agent provides the most robust clot formation as measured by the TEG. This study will consist of screening visit and 2-4 pharmacokinetic studies to determine the "best" bypassing agent based on the TEG results. Patients will then be assigned that bypassing agent and dose for the treatment of their bleeding episodes (Prophylaxis or On-demand). Each patient will be then followed for a period of 6 months to monitor short-term safety of those patients whose bypassing agent was modified.

Detailed Description

Currently, there are no laboratory assays that can assess the pharmaceutical activity of the available agents known collectively as bypassing agents, which negatively impacts the treating physician's ability to manage these patients, leaving decisions on the dosing regimen to trial and error. Both agents, FEIBA and recombinant activated factor VII (rFVIIa), are approved for the treatment of bleeding in inhibitor patients with recommended dosing regimens that are based on clinical trials. However, a significant amount of "experimenting" with other dosing regimens is used by physicians and patients.

The goal of this project is to demonstrate that TEG is an excellent biomarker for predicting, managing and individualizing the treatment with FEIBA and rFVIIa of this rare and difficult to treat patient population.

Study Timeline

• Study First Submitted: 2016-12-19
• Study First Submitted QC: 2016-12-21
• Study First Posted: 2016-12-23
• Study Start: 2017-01
• Status Verified: 2018-01
• Last Update Submitted: 2018-01-26
• Last Update Posted: 2018-01-30
• Primary Completion: 2019-01
• Study Completion: 2019-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

Inclusion Criteria

1. Males, 4-60 years old, inclusive on Prophylaxis or On-Demand treatment
2. Diagnosis of Hemophilia with active titer inhibitors (> 0.6 BU)
3. Willing to alter their treatment regimen per study protocol

Exclusion Criteria

1. Bleeding disorder(s) other than hemophilia A with inhibitors
2. Thrombocytopenia (platelet count <100,000K/µL)
3. Any concurrent clinically significant major disease that, in the opinion of the investigator, would make the subject unsuitable for enrollment
4. Participation within the past 30 days in a clinical study involving investigational drugs
5. Planned major surgery within 30 days prior to screening or during the study period

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Severe Hemophilia A subjects w/ inhibitors	Thromboelastography-Guided Treatment Regimen	Males age 4-70 years diagnosed with severe hemophilia A with inhibitors who are currently treated with prophylaxis or on-demand treatment will be enrolled.

Primary Outcome Measures

Name	Time	Method
Elastic properties of a forming clot using thromboelastograph to determine best bypassing agent	6 months	This study will assess the feasibility of TEG-guided individualization of bypassing agent treatment of bleeding for severe hemophilia A patients with inhibitors.

Secondary Outcome Measures

Name	Time	Method
Thrombin generation assay measuring the formation of thrombin during clot formation	6 months	Thrombin generation assays will be performed to provide additional evidence supporting the TEG-guided individualization of bypassing agent treatment.
Number of participants with treatment-related adverse events	1 year	The study will monitor short-term safety of patients whose bypassing agent treatment has been modified.