# Type-2 or Not Type-2:  That is the (Therapeutic) Question

> **NIH NIH UG1** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $408,516

## Abstract

Severe, exacerbation-prone asthma impacts 5-10% of the asthma population and continues to have
substantial human and economic impact, with nearly 2 million emergency room visits and 0.5 million
hospitalizations per year. Evidence from the Severe Asthma Research Program (SARP) supports the
heterogeneity of severe asthma, with substantial evidence to suggest differentiation of these patients into 2
broad categories based on biomarker evidence for the presence/absence of Type(T)-2 (IL-4, 5, -13) associated
inflammation. Concurrent industry sponsored clinical trials have further supported this broad differentiation,
with evidence for substantial efficacy of T2-targeted biologic therapies including those targeted to IL-4/13 and
IL-5 pathways in T2Hi asthma patients. However, the best biomarkers to predict response to T2-targeted
therapies are not yet clear. Given their enormous costs, it is critical to better understand and identify those
who most need these medications, which ones to utilize first and in which patients. It is even more unclear
whether specific biomarkers in patients with no (using current biomarker) evidence for T2 inflammation exist or
whether they predict targeted biologic approaches for these patients. The adaptive design trial proposed here
will utilize currently accepted biomarkers, as well as additional exploratory bio-imaging and genetic markers to
predict the most efficacious and safe approaches for these broad (but then more specific) T2-phenotypes. We
therefore hypothesize that an adaptive trial design integrating T2 (and non-T2) biomarkers, targeted therapies
and clinically relevant outcomes will improve the understanding of the pathobiology of severe asthma
patients on medium to high dose inhaled corticosteroids (ICS), with or without long acting 𝛽𝛽2 agonists (LABA)
phenotypes and bring the most efficacious (and safest) medication to each severe asthma patient. We
propose a multiphase adaptive trial design in 800 poorly controlled, exacerbating and/or severe asthmatic
and/or oral corticosteroids (OCS). The 1st (run-in) phase will establish each participant's baseline over a 3-6
month period of time, while repeatedly measuring established and exploratory biomarkers. The data from this
run-in phase will be used to assign the patient to a T2Hi or -Lo molecular phenotype and inform the modeling
of predictive factors to be applied during the targeted treatment phase. The targeted treatment phase will
consist of 3 treatments, adaptively applied to the two broad T2 phenotypes, with the intention to support the
importance of potential T2 sub-phenotypes, such as a T2Hi/Mast cell-Hi and T2Lo/Metabolic. The 3
treatments will differ by starting T2 phenotype, but the primary endpoint for each intervention will be treatment
failure defined by a biomarker and clinical index. T2Hi interventions will sequentially include a CRTH2
antagonist, an anti-IL-4Receptor(R) antibody and a soluble TNF-α receptor, while T2Lo interventions will
includ...

## Key facts

- **NIH application ID:** 10221034
- **Project number:** 5UG1HL139098-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Sally E Wenzel
- **Activity code:** UG1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $408,516
- **Award type:** 5
- **Project period:** 2017-09-23 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10221034

## Citation

> US National Institutes of Health, RePORTER application 10221034, Type-2 or Not Type-2:  That is the (Therapeutic) Question (5UG1HL139098-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10221034. Licensed CC0.

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