SepsisPhase 2EMBRACENCT06694701
Emapalumab Treatment For Anticipated Clinical Benefit In Sepsis Driven By The Interferon-Gamma Endotype (The EMBRACE Trial)
A Phase 2 study testing Emapalumab-Izsg in people with Sepsis, run by Hellenic Institute for the Study of Sepsis at 24 sites in Greece.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis
- What is being tested?
- Emapalumab-Izsg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 75 participants
- Where
- 24 sitesGreece
- Study dates
- 22 Mar 2025to Nov 2026
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
24 sites in 1 country.
24 sites in 1 country
Greece24 sites
Intensive Care Unit, Alexandroupolis University General Hospital
Alexandroupoli
3rd University Department of Internal Medicine, Sotiria Chest Diseases Athens General Hospital
Athens
4th Department of Internal Medicine, ATTIKON University General Hospital
Athens
Intensive Care Unit I, KAT Attica General Hospital
Athens
Intensive Care Unit of 1st University Department Respiratory Medicine, Sotiria Chest Diseases Athens General Hospital
Athens
Intensive Care Unit of Center for Respiratory Failure, Sotiria Chest Diseases Athens General Hospital
Athens
Intensive Care Unit, Asklipieio Voulas General Hospital
Athens
Intensive Care Unit, Ippokrateio Athens General Hospital
Athens
Intensive Care Unit, Korgialeneio-Benakeio HRC Athens General Hospital
Athens
Intensive Care Unit, Laiko Athens General Hospital
Athens
New Multivalent Intensive Care Unit, Sotiria Chest Diseases Athens General Hospital
Athens
Ηigh Dependency Unit of Department of Clinical Therapeutics, Alexandra Athens General Hospital
Athens
1st Department of Internal Medicine, Thriasio Elefsis General Hospital
Elefsina, Attica
Intensive Care Unit, University General Hospital of Heraklion
Heraklion, Crete
Clinic of Intensive Care and Pulmonary Diseases, Aghioi Anargyroi Kifissia General Oncologic Hospital
Kifissia, Attica
Intensive Care Unit, Patras University General Hospital
Pátrai
1st Intensive Care Unit, G. Papanikolaou Thessaloniki General Hospital
Thessaloniki
Department of Anesthesiology and Intensive Care, AHEPA Thessaloniki University General Hospital
Thessaloniki
Intensive Care Unit, 424 General Military Training Hospital
Thessaloniki
Intensive Care Unit, Aghios Dimitrios Thessaloniki General Hospital
Thessaloniki
Intensive Care Unit, G. Gennimatas Thessaloniki General Hospital
Thessaloniki
Intensive Care Unit, Ippokrateio Thessaloniki General Hospital
Thessaloniki
Intensive Care Unit, Papageorgiou Thessaloniki General Hospital
Thessaloniki
Intensive Care Unit, Theageneio Thessaloniki Cancer Hospital
Thessaloniki
About this study
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.
Read the detailed description
The EMBRACE trial aims to generate proof-of-concept if treatment with emapalumab, a monoclonal antibody which blocks IFNγ signaling, may improve the outcome of patients with sepsis driven by the IDS endotype. In EMBRACE, two different dose regimens of emapalumab are administered in order to: a) investigate which dose regimen may provide most of efficacy in the decrease of SOFA score, a new endpoint for sepsis suggested already by others; b) investigate which dose regimen better attains the pharmacodynamic goal of emapalumab defined as the decrease of blood CXCL9; and c) compare the efficacy of the two dose regimens with placebo treated patients.
- Conditions
- Sepsis
- Being tested
- Emapalumab-Izsg, Placebo
- Keywords
- Severe infections, IFNγ, IFNγ-Drive Sepsis, emapalumab, interferon-gamma
- Medical subject headings
- Sepsis, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emapalumab-IzsgDrug
Also called Emapalumab Group 1
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.
Emapalumab-IzsgDrug
Also called Emapalumab Group 2
The drug is administered at a dose of 6mg/kg of body weight on day 0, 6mg/kg of body weight on day 3, 6mg/kg of body weight on day 6 and repeated dosing of 3mg/kg of body weight is provisioned for days 9, 12, 15, 19, 23 and 27 provided that the stopping rule does not apply.
PlaceboDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Standard-of-care (SoC) treatment and placebo drug. Receives: Drug: Placebo |
| Emapalumab Group 1 | Active comparator | SoC treatment and a low dose of emapalumab. Receives: Drug: Emapalumab-Izsg |
| Emapalumab Group 2 | Active comparator | SoC treatment and a high dose of emapalumab. Receives: Drug: Emapalumab-Izsg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Comparison of the rate of serious TEAEs and non-serious TEAEs between the three groups of treatment.
Measured: 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.
Measured: 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
Comparison of the change of the SOFA score from day 0 until day 7
Measured: From enrollment (day 0) to 8 days after enrollment (day 7).
28-day mortality
Measured: From enrollment to 28 days after enrollment.
The change of the SOFA score from 0 until day 28
Comparison of the change of the SOFA score from 0 until day 28
Measured: From enrollment to 28 days after enrollment.
The change of the SOFA score from 0 until EOT
Comparison of the change of the SOFA score from 0 until EOT
Measured: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
The pharmacokinetics of emapalumab
Comparison of the pharmacokinetics of emapalumab
Measured: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
The need to stop the study drug due to drop of the number of HLA-DR receptors on CD14-monocytes.
Comparison of the need to stop the study drug due to drop of the number of HLA-DR receptors on CD14-monocytes.
Measured: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
The circulating concentrations of IL-6, ferritin, IFNγ and CXCL9 over the days of treatment
Comparison of the circulating concentrations of IL-6, ferritin, IFNγ and CXCL9 over the days of treatment
Measured: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2024
- Study start22 Mar 2025
- Primary completionNov 2026 (estimated)
- Study completionNov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hellenic Institute for the Study of Sepsis
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Evangelos Giamarellos-Bourboulis, Study chair, Hellenic Institute for the Studies of Sepsis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06694701
- Sponsor's protocol ID
- EMBRACE
- Other IDs
- 2024-515255-38-00
- Acronym
- EMBRACE
- Status last verified
- Mar 2025
- First submitted
- 13 Nov 2024
- Last updated
- 19 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Emapalumab Treatment For Anticipated Clinical Benefit In Sepsis Driven By The Interferon-Gamma Endotype (The EMBRACE Trial)
- ClinicalTrials.gov ID
- NCT06694701
- Acronym / sponsor ID
- EMBRACE / EMBRACE
- Conditions
- Sepsis
- Keywords
- Severe infections, IFNγ, IFNγ-Drive Sepsis, emapalumab, interferon-gamma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Hellenic Institute for the Study of SepsisUniversity, hospital or other
- Study start
- 22 Mar 2025 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Nov 2026 (estimated)
- First posted
- 19 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The EMBRACE trial aims to generate proof-of-concept if treatment with emapalumab, a monoclonal antibody which blocks IFNγ signaling, may improve the outcome of patients with sepsis driven by the IDS endotype. In EMBRACE, two different dose regimens of emapalumab are administered in order to: a) investigate which dose regimen may provide most of efficacy in the decrease of SOFA score, a new endpoint for sepsis suggested already by others; b) investigate which dose regimen better attains the pharmacodynamic goal of emapalumab defined as the decrease of blood CXCL9; and c) compare the efficacy of the two dose regimens with placebo treated patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboStandard-of-care (SoC) treatment and placebo drug. |
| Emapalumab Group 1 | Active comparator | Drug: Emapalumab-IzsgSoC treatment and a low dose of emapalumab. |
| Emapalumab Group 2 | Active comparator | Drug: Emapalumab-IzsgSoC treatment and a high dose of emapalumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Emapalumab-IzsgAlso: Emapalumab Group 1The 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. | Drug | Emapalumab Group 1 |
| Emapalumab-IzsgAlso: Emapalumab Group 2The drug is administered at a dose of 6mg/kg of body weight on day 0, 6mg/kg of body weight on day 3, 6mg/kg of body weight on day 6 and repeated dosing of 3mg/kg of body weight is provisioned for days 9, 12, 15, 19, 23 and 27 provided that the stopping rule does not apply. | Drug | Emapalumab Group 2 |
| Placebo250ml 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 | Drug | Placebo |
Primary outcome
Decrease of SOFA score by the end-of-treatment
Time frame: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
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.
9 secondary outcomes
The rate of serious TEAEs and non-serious TEAEs
Time frame: 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.
Time frame: 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
Time frame: From enrollment (day 0) to 8 days after enrollment (day 7).
28-day mortality
Time frame: From enrollment to 28 days after enrollment.
The change of the SOFA score from 0 until day 28
Time frame: From enrollment to 28 days after enrollment.
The change of the SOFA score from 0 until EOT
Time frame: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
The pharmacokinetics of emapalumab
Time frame: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
The need to stop the study drug due to drop of the number of HLA-DR receptors on CD14-monocytes.
Time frame: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
The circulating concentrations of IL-6, ferritin, IFNγ and CXCL9 over the days of treatment
Time frame: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Evangelos Giamarellos-Bourboulis study chair
Hellenic Institute for the Studies of Sepsis
24 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Emapalumab-Izsg in people with Sepsis, run by Hellenic Institute for the Study of Sepsis at 24 sites in Greece.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 24 sites in Greece. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Decrease of SOFA score by the end-of-treatment (time frame: From enrollment to the end of treatment of the study drug for each of the study participants, ranging from 2 to 29 days.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2025.