Role of Eosinophil Surface Markers in Clinical Response and Effect of Eosinophil Depletion in Antigen-Driven Eosinophilic Disease

Project: Research project

Project Details

Description

Background

Hypereosinophilic syndrome (HES) is a rare disease characterized by markedly elevated peripheral blood eosinophils or tissue eosinophilia that leads to end organ damage and can be life-threatening. Treatment options are limited. There is interest in using anti-eosinophil biologics (developed for asthma) to treat this rare disease.

At my previous position at the National Institutes of Health, I was involved in an investigator-initiated phase 2 clinical trial of anti-IL5Ra (benralizumab; Fasenra) for HES in collaboration with Astra Zeneca. The positive findings were recently published (Kuang et al NEJM 2019), and the company is pursuing a phase 3 multi-center trial for this medication in HES (NCT04191304).

Phase 3 Benralizumab for HES

In the previous phase 2 trial, a number of parameters were examined to assess whether they were predictors of clinical response in the patients, and only HES clinical subtype was found to be predictive (Kuang et al NEJM 2019). This will be examined/confirmed in the larger multi-center trial.

We are interested in understanding whether surface markers on the eosinophil, the targeted cell of the drug, play a role in patient clinical response. In the previous phase 2 study, only eosinophil expression of IL5Ra expression was examined (and was not predictive), but other activation or surface markers on the eosinophils remain to be explored.

In the previous trial, it was observed that patients with gastrointestinal manifestations of eosinophilic disease (HES/EGID overlap) had a differential response depending on whether they had evidence of food allergy or food-driven eosinophilic disease. This can be seen by examining for the presence of pathogenic effector Th2 cells by flow cytometry and change in inflammatory cytokine production. We are interested in understanding if this is confirmed in a larger cohort of patients from this multi-center phase 3 trial.

Scope of Work

We will collaborate on the multi-center study by analyzing coded patient samples that would be sent to us from a central processing facility or from the clinical sites.
StatusActive
Effective start/end date6/1/216/1/24

Funding

  • AstraZeneca UK Limited (Agmt 06/01/21)

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