# NATIENS: A Phase III Randomized Double Blinded Study to Determine the Mechanisms and Optimal Management of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

> **NIH NIH U01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $3,535,017

## Abstract

PROJECT SUMMARY
 Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are severe, life-threatening
immunologically mediated adverse drug reactions representing the same disease across a spectrum of severity.1
There is currently no evidence-based standard of care treatment for SJS/TEN. Preventive efforts have been
fueled by strong associations between the HLA Class I allele HLA-B*15:02 which has led to implementation of
cost-effective pre-treatment genetic screening programs in many Southeast Asian countries.2,3 However, the
lower prevalence (<1%) and negative predictive value of this HLA allele in European American, Hispanic
American, and African American populations, and the lack of currently defined HLA associations with drugs
commonly used and associated with SJS/TEN in the United States has left many evidence gaps and
implementation hurdles.4 The scientific premise of this study is that the most efficacious treatment will
impact cellular immune responses mediating, related biomarkers and clinical outcomes of SJS/TEN. We
have assembled the North American Therapeutics in Epidermal Necrolysis Syndrome (NATIENS) study,
a group of 22 sites across the United States to conduct the first multicenter double-blind double dummy
randomized controlled assessment of cyclosporine or etanercept or supportive care. The controlled
design will afford the opportunity to collect and assay multiple samples in each treatment arm, in both
the acute and convalescent phase, with the aim to discover new strategies for prevention, early
diagnosis and targeted treatment. We will use integrated multi-omic, single-cell and high-throughput
in-vitro screening approaches to determine the genetic basis, immunopathology and antigen specificity
of drug-induced SJS/TEN. In Specific Aim 1 we will establish the most clinically effective therapy for SJS/TEN
through the NATIENS multi-centered, double-blind double-dummy randomized controlled trial with a planned
accrual of 267 patients over 5 enrollment years to determine whether etanercept and/or cyclosporine have
benefit over supportive care for the measured primary outcome of complete re-epithelialization. In Specific Aim
2 we will use genome-wide sequencing, high-resolution HLA sequencing, transcriptomic, and cytokine profiling
to identify genetic and biological markers that predict risk and outcome for SJS/TEN. In Specific Aim 3 We will
study the immune phenotype of cells in the skin, blister fluid and peripheral blood in acute SJS/TEN based on
single-cell RNA and protein expression. Using the dominantly represented T-cell receptor (TCR) in the blister
fluid we will use a high throughput in-vitro screening approach to identify specific epitopes recognized by CD8+
T cells at the site of SJS/TEN tissue damage.5 Our study will be the first to examine in a double-blind
randomized controlled design both management and mechanisms of SJS/TEN. This will lead to new ways
to prevent, diagnosis and treat SJS/TEN, and will cr...

## Key facts

- **NIH application ID:** 10217036
- **Project number:** 5U01AI154659-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Elizabeth Phillips
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,535,017
- **Award type:** 5
- **Project period:** 2020-07-15 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10217036

## Citation

> US National Institutes of Health, RePORTER application 10217036, NATIENS: A Phase III Randomized Double Blinded Study to Determine the Mechanisms and Optimal Management of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis (5U01AI154659-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10217036. Licensed CC0.

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