Clinical trial NCT05281718: Factor IX as Adjunctive Therapy to Emicizumab (EMIX)
Official title: An in Vitro Pilot Study of the Role of Factor IX as an Alternative to Bypassing Agents in the Treatment of Breakthrough Bleeds in Patients With Hemophilia A and Inhibitors Treated With Emicizumab.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Hemophilia A
Keywords: Hemophilia A with inhibitors
In vitro
Emicizumab
Lead sponsor: Tulane University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
First posted: 2022-03-16
Enrollment: 12
Sex: MALE
Minimum age (years): 12
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open Label
Primary purpose: BASIC_SCIENCE

Brief summary: This trial will enroll patients with severe hemophilia A. Experiments will be run in vitro by spiking patients' blood with different molecules (currently used and theoretically proposed as adjunctive therapy to emicizumab), therefore no more than minimal direct risk to patients is expected. This is a pilot preclinical study.

Detailed description: The study aims to determine the hemostatic effect of different Factor IX (FIX) concentrates when added to the plasma of patients on emicizumab prophylaxis and compare it to the hemostatic effect obtained with the addition of bypassing agents (activated prothrombin complex aPCC, and recombinant VIIa rVIIA, recombinant porcine FVIII).

The investigators will study the hemostatic effect using Thrombin Generation assay (CAT) in the presence of different concentrations of FIX concentrates. The investigators will compare the hemostatic effect of added FIX to the effect of added bypassing agents (activated prothrombin complex aPCC, and recombinant VIIa rVIIA, recombinant porcine FVIII)

Plasma will be collected from patients with hemophilia A and inhibitors treated with Emicizumab, a group of plasma samples will be spiked with different concentrations of Factor IX. Thrombin generation profiles will be obtained using CAT.

Another group of plasma samples will be spiked with different concentrations of by passing agents (activated prothrombin complex aPCC, and recombinant VIIa rVIIA, recombinant porcine FVIII). Thrombin generation profiles will be obtained using CAT.

Eligibility criteria: Inclusion Criteria:

* Signed Informed Consent/Assent Form
* Male patients, Age 12 years and older at time of signing Informed Consent Form
* Ability to comply with the study protocol, in the investigator's judgment
* Diagnosis of severe hemophilia A and are receiving emicizumab prophylaxis, on a weekly maintenance regimen

Exclusion Criteria:

* Not able to sign consent
* Not willing to provide extra blood for the experiments.
* Patients carrying the diagnoses of other coagulopathies in addition to hemophilia A
* Patients that have received any hemostatic agent within 5 half-lives of the blood draw. This applies to any agent that might have been used for any reason prior to the blood draw and might affect the global hemostasis.

Primary outcomes:
measure: Determine the homeostatic effect of adding Factor IX concentrate to the plasma of patients with Hemophilia A with inhibitors on emicizumab using peak thrombin
timeFrame: 1 Year
measure: Determine the hemostatic effect of Factor IX concentrates and recombinant porcine FVIII when added to the plasma of patients with Hemophilia A with inhibitors on emicizumab using peak thrombin
timeFrame: 1 Year
measure: Determine the homeostatic effect of adding Factor IX concentrate to the plasma of patients with Hemophilia A with inhibitors on emicizumab using Endogenous Thrombin Potential (ETP)
timeFrame: 1 Year
measure: Determine the hemostatic effect of Factor IX concentrates and recombinant porcine FVIII when added to the plasma of patients with Hemophilia A with inhibitors on emicizumab using Endogenous Thrombin Potential (ETP)
timeFrame: 1 Year
Secondary outcomes:
Other outcomes:
Locations:
city: Metairie
country: United States
facility: Tulane University Lakeside Hospital and Clinics
state: Louisiana
city: New Orleans
country: United States
facility: University Medical Center New Orleans
state: Louisiana
Study officials:
affiliation: Tulane University
name: Maissa Janbain, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: