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

NCT06694701 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: EMBRACE2024-515255-38-00
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 24

Brief Summary

EMBRACE is a double-blind, randomized, placebo-controlled, phase IIa study that will be conducted in multiple Intensive Care Units (ICUs) and departments of Internal Medicine across Greece. It aims to investigate if treatment with emapalumab, a monoclonal antibody which blocks IFNγ, may improve the outcome of patients with sepsis driven by the IDS (endotype of IFNγ-driven sepsis) endotype. EMBRACE also aims to identify the best dosing regimen of emapalumab for the management of IDS.

Conditions

Sepsis

Keywords

Severe infections; IFNγ; IFNγ-Drive Sepsis; emapalumab; interferon-gamma

Outcome Measures

Primary Outcomes (1)

• Decrease of SOFA score by the end-of-treatment

  The study primary endpoint is the decrease of SOFA score by the end-of-treatment (EOT). This is defined as either a) at least 1.4 points decrease of mean SOFA score calculated between days 1 and EOT from SOFA score of day 0; OR b) at least 2 points decrease of SOFA at EOT from day 0.

  From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.

Secondary Outcomes (9)

• The rate of serious TEAEs and non-serious TEAEs

  From enrollment to the end of observation of each of the study participants, which is 120 days plus or minus 3 days, after each participant's enrollment.

• The number of doses required in each group to achieve the SOFA score response by the EOT.

  From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.

• The change of the SOFA score from day 0 until day 7

  From enrollment (day 0) to 8 days after enrollment (day 7).

• 28-day mortality

  From enrollment to 28 days after enrollment.

• The change of the SOFA score from 0 until day 28

  From enrollment to 28 days after enrollment.

Other Outcomes (5)

• Comparison between the three groups of treatment for the proteomic profile over treatment

  From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.

• The comparisons between the three groups of treatment for the change of the transcriptomic profile over treatment

  From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.

• The diagnostic performance of the point-of-care SepsisLoop for SII compared to the absolute count of HLA-DR receptor on CD45/CD14-monocytes.

  From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Standard-of-care (SoC) treatment and placebo drug.

Drug: Placebo

Emapalumab Group 1

ACTIVE COMPARATOR

SoC treatment and a low dose of emapalumab.

Drug: Emapalumab-Izsg

Emapalumab Group 2

ACTIVE COMPARATOR

SoC treatment and a high dose of emapalumab.

Drug: Emapalumab-Izsg

Interventions

Emapalumab-Izsg DRUG

The drug is administered at a dose of 6mg/kg of body weight on day 0 and repeated dosing of 3mg/kg of body weight is provisioned for days 3, 6, 9, 12, 15, 19, 23 and 27 provided that the stopping rule does not apply.

Also known as: Emapalumab Group 1

Emapalumab Group 1

Placebo DRUG

250ml of 0.9% sodium chloride. The drug is administered on day 0 and repeated dosing is provisioned for days 3, 6, 9, 12, 15, 19, 23 and 27 provided that the stopping rule does not apply

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Hellenic Institute for the Study of Sepsis: lead

Study Sites (24)

1st Department of Internal Medicine, Thriasio Elefsis General Hospital

Elefsina, Attica, Greece

Location

Clinic of Intensive Care and Pulmonary Diseases, Aghioi Anargyroi Kifissia General Oncologic Hospital

Kifissia, Attica, Greece

Location

Intensive Care Unit, University General Hospital of Heraklion

Heraklion, Crete, Greece

Location

Intensive Care Unit, Alexandroupolis University General Hospital

Alexandroupoli, Greece

Location

3rd University Department of Internal Medicine, Sotiria Chest Diseases Athens General Hospital

Athens, Greece

Location

4th Department of Internal Medicine, ATTIKON University General Hospital

Athens, Greece

Location

Intensive Care Unit I, KAT Attica General Hospital

Athens, Greece

Location

Intensive Care Unit of 1st University Department Respiratory Medicine, Sotiria Chest Diseases Athens General Hospital

Athens, Greece

Location

Intensive Care Unit of Center for Respiratory Failure, Sotiria Chest Diseases Athens General Hospital

Athens, Greece

Location

Intensive Care Unit, Asklipieio Voulas General Hospital

Athens, Greece

Location

Intensive Care Unit, Ippokrateio Athens General Hospital

Athens, Greece

Location

Intensive Care Unit, Korgialeneio-Benakeio HRC Athens General Hospital

Athens, Greece

Location

Intensive Care Unit, Laiko Athens General Hospital

Athens, Greece

Location

New Multivalent Intensive Care Unit, Sotiria Chest Diseases Athens General Hospital

Athens, Greece

Location

Ηigh Dependency Unit of Department of Clinical Therapeutics, Alexandra Athens General Hospital

Athens, Greece

Location

Intensive Care Unit, Patras University General Hospital

Pátrai, Greece

Location

1st Intensive Care Unit, G. Papanikolaou Thessaloniki General Hospital

Thessaloniki, Greece

Location

Department of Anesthesiology and Intensive Care, AHEPA Thessaloniki University General Hospital

Thessaloniki, Greece

Location

Intensive Care Unit, 424 General Military Training Hospital

Thessaloniki, Greece

Location

Intensive Care Unit, Aghios Dimitrios Thessaloniki General Hospital

Thessaloniki, Greece

Location

Intensive Care Unit, G. Gennimatas Thessaloniki General Hospital

Thessaloniki, Greece

Location

Intensive Care Unit, Ippokrateio Thessaloniki General Hospital

Thessaloniki, Greece

Location

Intensive Care Unit, Papageorgiou Thessaloniki General Hospital

Thessaloniki, Greece

Location

Intensive Care Unit, Theageneio Thessaloniki Cancer Hospital

Thessaloniki, Greece

Location

MeSH Terms

Conditions

Sepsis; Infections

Condition Hierarchy (Ancestors)

Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Evangelos Giamarellos-Bourboulis

  Hellenic Institute for the Studies of Sepsis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2024
• First Posted: November 19, 2024
• Study Start: March 22, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: November 19, 2025

Record last verified: 2025-03

Locations

GR (24)