Severe Hepatitis Intervention With Emapalumab for Liver Disease

NCT07744919 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: SHIELD
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to see whether a medicine called emapalumab, a monoclonal antibody, is safe and works well for patients aged 1 year and older who have indeterminate severe hepatitis with T-cell activation and have not responded well to steroids or still need them. This study has a Screening Cohort and an Intervention Cohort. The Screening Cohort will enroll patients with severe hepatitis of all etiologies to observe and collect research samples. Patients enrolled on the Screening Cohort will be asked to participate on the Intervention Cohort if they develop steroid-refractory/ dependent indeterminate severe hepatitis (iSH-T). Additionally, patients may bypass the Screening Cohort and enroll directly in the Intervention Cohort if they already meet its eligibility criteria. Patients in the Intervention Cohort will be treated with emapalumab.

Conditions

Hepatitis

Keywords

Hepatitis; Emapalumab; iSH-T; anti-IFN-gamma monoclonal antibody; Severe Hepatitis Associated with T-Cell Activation; Severe Hepatitis; Steroid-refractory hepatitis; steroid-dependent hepatitis; relapse hepatitis; Severe Hepatic Injury

Outcome Measures

Primary Outcomes (1)

• Incidence of Liver Failure

  INR \>2 on two consecutive occasions without hepatic encephalopathy (HE), or INR ≥1.5 with evidence of HE

  30, 90, and 180 days after the start of emapalumab

Secondary Outcomes (18)

• Complete Response (CR)

  throughout study participation/ up to 180 days

• Cytokine and Chemokine Profiling

  through study participation/ up to 180 days

• Emapalumab Immunologic Effects

  through study completion/ up to 180 days

• Incidence and Severity of Adverse Events

  from first emapalumab dose through study completion, up to 180 days

• Population Summary Measure

  throughout study participation/ up to 180 days

Study Arms (1)

Intervention Cohort

EXPERIMENTAL

Participants on the Intervention Cohort will receive a combination of immunomodulatory regimen using emapalumab and methylprednisolone (or prednisone equivalent), aimed at controlling severe immune-mediated hepatitis and preventing progression to liver failure. Participants will be monitored closely for clinical improvement, laboratory normalization, and adverse events throughout the 56-day treatment period, with continued follow-up through Day 180 to assess long-term outcomes, including relapse, liver failure, survival, and safety.

Drug: Emapalumab

Interventions

Emapalumab DRUG

Participants on the Intervention Cohort will receive a combination of immunomodulatory regimen using emapalumab and methylprednisolone (or prednisone equivalent), aimed at controlling severe immune-mediated hepatitis and preventing progression to liver failure.

Intervention Cohort

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age: Participants must be ≥ 1 year of age at the time of screening.
• Evidence of Severe Hepatic Injury of all etiology (not just iSH/ iSH-T): Serum alanine aminotransferase (ALT) ≥ 1000 U/L documented within 7 days prior to enrollment.

You may not qualify if:

• Any condition impairing informed consent/assent or protocol compliance
• Steroid-refractory, steroid-dependent, or relapse of hepatitis after stopping steroids and have an Indeterminate etiology of hepatitis based on standard of care, age appropriate evaluation
• Age: ≥ 1 year
• ALT ≥ 1000 U/L prior to initiation of any immune modulatory therapy
• Evidence of T-cell activation at initial diagnosis, as indicated by one of the following:
• sIL2R \> 2× upper limit of normal (ULN)
• CXCL9 \> 5× ULN
• CD8+ T-cell infiltration in the liver
• INR \< 2.0 without evidence of hepatic encephalopathy
• Patients with known Liver failure (defined as INR \>2 on two consecutive occasions without hepatic encephalopathy (HE), or INR ≥1.5 with evidence of HE)
• Evidence of chronic liver disease or parenchymal nodularity as demonstrated on imaging (US, CT, or MRI)
• Evidence of hepatic encephalopathy
• Severe acquired aplastic anemia at presentation
• Organ dysfunction assessment defined below:
• Renal dysfunction: eGFR \< 30 mL/min/1.73m² or

Sponsors & Collaborators

• Children's Healthcare of Atlanta: lead
• Sobi, Inc.: collaborator

Study Sites (1)

Arthur M. Blank Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Hepatitis

Interventions

Emapalumab

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Central Study Contacts

Shanmuganathan Chandrakasan, MD

CONTACT

404-727-8877; Shanmuganathan.Chandrakasan@emory.edu

Maria Frazer

CONTACT

4047856162; maria.frazer@choa.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2026
• First Posted: August 4, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): September 1, 2031
• Study Completion (Estimated): September 1, 2032
• Last Updated: August 4, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will share

Locations

US (1)