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Treatment with emapalumab for sepsis driven by interferon-gamma

Emapalumab Treatment For Anticipated Clinical Benefit In Sepsis Driven By The Interferon-Gamma Endotype (The EMBRACE Trial)

Phase 2 Interventional Hellenic Institute for the Study of Sepsis · NCT06694701

This study is testing if a new drug called emapalumab can help people with sepsis caused by interferon-gamma feel better and improve their chances of recovery.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment75 (estimated)
Ages18 Years and up
SexAll
SponsorHellenic Institute for the Study of Sepsis Academic / other
Drugs / interventionstocilizumab, emapalumab, baricitinib
Locations24 sites (Elefsina, Attiki and 23 other locations)
Trial IDNCT06694701 on ClinicalTrials.gov

What this trial studies

The EMBRACE trial is a double-blind, randomized, placebo-controlled phase IIa study conducted in multiple ICUs and internal medicine departments across Greece. It aims to evaluate the efficacy of emapalumab, a monoclonal antibody that blocks interferon-gamma (IFNγ), in improving outcomes for patients with sepsis driven by the IFNγ endotype. The study will compare two different dosing regimens of emapalumab against a placebo to determine which regimen is most effective in reducing the SOFA score and achieving pharmacodynamic goals. This trial seeks to provide proof-of-concept for the therapeutic potential of emapalumab in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older diagnosed with various types of pneumonia or infections that meet the criteria for sepsis as defined by the Sepsis-3 guidelines.

Not a fit: Patients with sepsis not driven by the interferon-gamma endotype or those with contraindications to emapalumab may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival rates and clinical outcomes for patients suffering from sepsis driven by the interferon-gamma endotype.

How similar studies have performed: While this approach is novel in the context of sepsis driven by the interferon-gamma endotype, other studies have explored the use of monoclonal antibodies in sepsis with varying degrees of success.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Provide written informed consent
* Adults (≥18 years) of male or female sex
* Diagnosis of community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), intrabdominal infection (IAI), acute pyelonephritis (AP), primary bloodstream infection (BSI) and viral respiratory infections.
* Sepsis defined by the Sepsis-3 definitions. This is defined as any new infection which is accompanied by an increase of the total baseline SOFA score by at least 2 points. The total baseline SOFA score is calculated by the medical comorbidities and by the evaluation of clinical variables before the sepsis episode in the case of hospital-acquired sepsis. In the case of patients with unknown baseline SOFA score, sepsis is defined as any new infection accompanied by total SOFA score 2 or more.
* Willingness to use effective contraceptive methods during the period from the start of the study drug to 6 months after the administration of the last dose of the study drug, in patients of reproductive age.
* Serological documentation of IDS defined as detectable blood IFNγ and CXCL9 more than 2,200 pg/ml. IFNγ and CXCL9 are measured in the central study lab by an enzyme immunosorbent assay.
* Absence of sepsis-induced immunoparalysis (SII). This is defined as ≥8000 of HLA-DR receptors on CD45/CD14-monocytes measured by flow-cytometry in the central lab using the BD™ fluorescence assay9.

Exclusion Criteria:

* Body weight more than 104 kg
* Intake of any other biological during the last 30 days prior screening except for the intake of anakinra or tocilizumab for patients with active infection by SARS-CoV-2
* Intake of any Janus kinase inhibitors during the last 30 days prior screening except for the intake of baricitinib for patients with active infection by SARS-CoV-2
* Known active infection by Mycobacterium tuberculosis or other mycobacteria. These patients may be enrolled in the trial if treatment against infection by Mycobacterium tuberculosis or other mycobacteria has been initiated
* Known active infection by VZV (varicella zoster virus) or by Histoplasma capsulatum or by Leishmania spp. These patients may be enrolled in the trial if treatment against infection by VZV or Histoplasma capsulatum has been initiated
* Known active infection by the hepatitis B virus, by the hepatitis C virus and by cytomegalovirus
* Vaccination the last 12 weeks before screening with BCG vaccine
* Vaccination with any live or attenuated live vaccine (other than BCG) the last 12 weeks before screening
* Known allergy or hypersensitivity reactions to emapalumab
* Patients living with the human immunodeficiency virus (HIV)
* Patients with stage IV solid or hematologic malignancy
* Patients with neutropenia (less than 1,000 neutrophils/mm3)
* Patients transplanted for solid organ or stem cells
* Pregnancy or lactation
* Participation in any other interventional trial the last 28 days prior to day 1

Where this trial is running

Elefsina, Attiki and 23 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions SepsisSevere infectionsIFNγIFNγ-Drive Sepsisemapalumabinterferon-gamma
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.