Clinical trial • Phase II • Infectious Disease|Respiratory

EMAPALUMAB for Sepsis

Phase II trial of EMAPALUMAB for Sepsis.

Overview

Trial Therapeutic Area
Infectious Disease|Respiratory
Trial Disease
Sepsis
Trial Stage
Phase II
Drug Modality
Monoclonal antibody|Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
02-07-2024
First CTIS Authorization Date
21-10-2024

Trial design

Sodium Chloride Injection/ DEMO 0,9% w/v (placebo) administered by intravenous infusion; product record lists dose units ml with max daily amount 250 ml, max total amount 2250 ml, max treatment period 28 days.-controlled Phase II trial across 29 sites in Greece.

Comparator
Sodium Chloride Injection/ DEMO 0,9% w/v (placebo) administered by intravenous infusion; product record lists dose units ml with max daily amount 250 ml, max total amount 2250 ml, max treatment period 28 days.
Biomarker Stratified
True, biomarkers: blood IFNγ and CXCL9; IDS defined as detectable IFNγ and CXCL9 >2,200 pg/ml (patients must have serological documentation of IDS).
Target Sample Size
75
Trial Duration For Participant
28

Eligibility

Recruits 75 Vulnerable population flag selected in the registry. Inclusion requires "Provide written informed consent" and participants are adults (≥18 years). Subject information and informed consent forms are available in Greek and English (multiple ICF documents listed). No explicit statement in the provided data about assent or legally authorised representative/proxy consent procedures is available..

Pregnancy Exclusion
Pregnancy or lactation
Vulnerable Population
Vulnerable population flag selected in the registry. Inclusion requires "Provide written informed consent" and participants are adults (≥18 years). Subject information and informed consent forms are available in Greek and English (multiple ICF documents listed). No explicit statement in the provided data about assent or legally authorised representative/proxy consent procedures is available.

Inclusion criteria

  • {"criterion_text":"- Provide written informed consent\n- Adults (≥18 years) of male or female sex\n- 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.\n- 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.\n- 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.\n- 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\n- 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 assay."}

Exclusion criteria

  • {"criterion_text":"- 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\n- Participation in any other interventional trial the last 28 days prior to day 0\n- 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\n- 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\n- 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.\n- Vaccination the last 12 weeks before screening with BCG vaccine\n- Body weight more than 125 kg\n- Vaccination with any live or attenuated live vaccine (other than BCG) the last 12 weeks before screening\n- Known allergy or hypersensitivity reactions to emapalumab\n- Patients living with the human immunodeficiency virus (HIV)\n- Patients with stage IV solid or hematologic malignancy\n- Known active infection by the hepatitis B virus, by the hepatitis C virus and by cytomegalovirus\n- Patients with neutropenia (less than 1,000 neutrophils/mm3)\n- Patients transplanted for solid organ or stem cells\n- Pregnancy or lactation"}

Endpoints

Primary endpoints

  • {"endpoint_text":"- 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.","definition_or_measurement_approach":"Decrease in SOFA score measured from day 0 to EOT. Option (a) compares the mean SOFA between days 1 and EOT vs day 0 (≥1.4 point decrease) or (b) absolute decrease of ≥2 points at EOT versus day 0."}
  • {"endpoint_text":"- Patients dying before the EOT are considered not meeting the primary endpoint. EOT is defined as the day of end of treatment of the study drug for each of the study participants. For patients requiring dosing by day 27, the decrease of the SOFA score is evaluated on day 28.","definition_or_measurement_approach":"Deaths prior to EOT count as failure to meet the primary endpoint. EOT defined as day of end of study drug treatment; for patients dosed through day 27 the SOFA change is assessed on day 28."}

Secondary endpoints

  • {"endpoint_text":"- The number of doses required in each group to achieve the SOFA score response by the EOT","definition_or_measurement_approach":"Count of administered doses per group required to meet the SOFA response criteria by EOT."}
  • {"endpoint_text":"- 28-day mortality","definition_or_measurement_approach":"All-cause mortality measured at 28 days."}

Recruitment

Planned Sample Size
75
Recruitment Window Months
24
Consent Approach
Written informed consent is required (inclusion criterion: "Provide written informed consent"). Participants are adults (≥18 years). Subject information and informed consent forms are available in Greek and English (multiple ICF documents listed). The provided data does not specify proxy consent, assent, or other language versions beyond Greek and English.

Geography

Total Number Of Sites
29
Total Number Of Participants
75

Greece

Earliest CTIS Part Ii Submission Date
12-09-2024
Latest Decision Or Authorization Date
20-10-2025
Processing Time Days
403
Number Of Sites
29
Number Of Participants
75

Sites

Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
New Multivalent Intensive Care Unit
Principal Investigator Name
Maria Daganou
Principal Investigator Email
mdaganou@hotmail.com
Contact Person Name
Maria Daganou
Contact Person Email
mdaganou@hotmail.com
Site Name
Ippokratio General Hospital Of Thessaloniki
Department Name
Intensive Care Unit
Principal Investigator Name
Eleni Mouloudi
Principal Investigator Email
elmoulou@yahoo.gr
Contact Person Name
Eleni Mouloudi
Contact Person Email
elmoulou@yahoo.gr
Site Name
424 Military General Training Hospital
Department Name
Intensive Care Unit
Principal Investigator Name
Ioannis Katsiadramis
Principal Investigator Email
ikatsiadramis@yahoo.gr
Contact Person Name
Ioannis Katsiadramis
Contact Person Email
ikatsiadramis@yahoo.gr
Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
1st Department of Internal and Pulmonary Medicine
Principal Investigator Name
Nikoleta Rovina
Principal Investigator Email
nikrovina@med.uoa.gr
Contact Person Name
Nikoleta Rovina
Contact Person Email
nikrovina@med.uoa.gr
Site Name
General Hospital Of Eleusina Thriasio
Department Name
1st Department of Internal Medicine
Principal Investigator Name
Styliani Sympardi
Principal Investigator Email
lianasympa@hotmail.com
Contact Person Name
Styliani Sympardi
Contact Person Email
lianasympa@hotmail.com
Site Name
Ippokratio General Hospital Of Thessaloniki
Department Name
2nd Propaedeutic Department of Internal Medicine
Principal Investigator Name
Michail Doumas
Principal Investigator Email
michalisdoumas@yahoo.co.uk
Contact Person Name
Michail Doumas
Contact Person Email
michalisdoumas@yahoo.co.uk
Site Name
General Hospital Of Thessaloniki Papageorgiou
Department Name
Intensive Care Unit
Principal Investigator Name
Domniki Liatsi
Principal Investigator Email
domliatsi@yahoo.gr
Contact Person Name
Domniki Liatsi
Contact Person Email
domliatsi@yahoo.gr
Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
1st Department of Internal and Pulmonary Medicine
Principal Investigator Name
Zafeiria Mastora
Principal Investigator Email
nikrovina@med.uoa.gr
Contact Person Name
Zafeiria Mastora
Contact Person Email
nikrovina@med.uoa.gr
Site Name
University General Hospital Of Ioannina
Department Name
Intensive Care Unit
Principal Investigator Name
Ioannis Koulouras
Principal Investigator Email
vpkoulouras@yahoo.gr
Contact Person Name
Ioannis Koulouras
Contact Person Email
vpkoulouras@yahoo.gr
Site Name
Kat Attica General Hospital
Department Name
Intensive Care Unit I
Principal Investigator Name
Maria Theodorakopoulou
Principal Investigator Email
mariatheodor10@gmail.com
Contact Person Name
Maria Theodorakopoulou
Contact Person Email
mariatheodor10@gmail.com
Site Name
Theageneio Cancer Hospital
Department Name
Intensive Care Unit
Principal Investigator Name
Souzana Anisoglou
Principal Investigator Email
souzanis@freemail.gr
Contact Person Name
Souzana Anisoglou
Contact Person Email
souzanis@freemail.gr
Site Name
General Hospital Of Athens Korgialenio Benakio H.R.C.
Department Name
Intensive Care Unit
Principal Investigator Name
Maria Patrani
Principal Investigator Email
mpatrani@gmail.com
Contact Person Name
Maria Patrani
Contact Person Email
mpatrani@gmail.com
Site Name
General Hospital Of Thessaloniki O Agios Dimitrios
Department Name
Intensive Care Unit
Principal Investigator Name
Glykeria Vlachogianni
Principal Investigator Email
glykav@otenet.gr
Contact Person Name
Glykeria Vlachogianni
Contact Person Email
glykav@otenet.gr
Site Name
University General Hospital Attikon
Department Name
4th Department of Internal Medicine
Principal Investigator Name
Evangelos Giamarellos-Bourboulis
Principal Investigator Email
egiamarel@med.uoa.gr
Contact Person Name
Evangelos Giamarellos-Bourboulis
Contact Person Email
egiamarel@med.uoa.gr
Site Name
University General Hospital Of Alexandroupoli
Department Name
Intensive Care Unit
Principal Investigator Name
Vasileios Papaioannou
Principal Investigator Email
vapapa@med.duth.gr
Contact Person Name
Vasileios Papaioannou
Contact Person Email
vapapa@med.duth.gr
Site Name
University General Hospital Of Alexandroupoli
Department Name
2nd Department of Internal Medicine
Principal Investigator Name
Periklis Panagopoulos
Principal Investigator Email
ppanago@med.duth.gr
Contact Person Name
Periklis Panagopoulos
Contact Person Email
ppanago@med.duth.gr
Site Name
General Hospital Of Thessloniki G Gennimatas
Department Name
Intensive Care Unit
Principal Investigator Name
Eleni Antoniadou
Principal Investigator Email
eleni.antoniadou@gmail.com
Contact Person Name
Eleni Antoniadou
Contact Person Email
eleni.antoniadou@gmail.com
Site Name
Asklepieion Voulas General Hospital
Department Name
Intensive Care Unit
Principal Investigator Name
Aikaterini Ioakeimidou
Principal Investigator Email
katioakim@gmail.com
Contact Person Name
Aikaterini Ioakeimidou
Contact Person Email
katioakim@gmail.com
Site Name
General University Hospital Of Patras
Department Name
Intensive Care Unit
Principal Investigator Name
Vasileios Karamouzos
Principal Investigator Email
vkaramouzos@hotmail.com
Contact Person Name
Vasileios Karamouzos
Contact Person Email
vkaramouzos@hotmail.com
Site Name
University General Hospital Of Heraklion
Department Name
Intensive Care Unit
Principal Investigator Name
Evmorfia Kondyli
Principal Investigator Email
kondylie@uoc.gr
Contact Person Name
Evmorfia Kondyli
Contact Person Email
kondylie@uoc.gr
Site Name
Hippokration Hospital
Department Name
Intensive Care Unit
Principal Investigator Name
Georgios Kofinas
Principal Investigator Email
georgekofinas@gmail.com
Contact Person Name
Georgios Kofinas
Contact Person Email
georgekofinas@gmail.com
Site Name
Laiko General Hospital Of Athens
Department Name
Intensive Care Unit
Principal Investigator Name
Elissavet Paramythiotou
Principal Investigator Email
lparamyth61@hotmail.com
Contact Person Name
Elissavet Paramythiotou
Contact Person Email
lparamyth61@hotmail.com
Site Name
Geniko Nosokomeio Thessalonikis George Papanikolaou
Department Name
1st Intensive Care Unit
Principal Investigator Name
Athina Lavrentieva
Principal Investigator Email
alavrenti@gmail.com
Contact Person Name
Athina Lavrentieva
Contact Person Email
alavrenti@gmail.com
Site Name
General Hospital Of Thessaloniki Papageorgiou
Department Name
3rd Department of Internal Medicine
Principal Investigator Name
Vasileios Kotsis
Principal Investigator Email
vkotsis@auth.gr
Contact Person Name
Vasileios Kotsis
Contact Person Email
vkotsis@auth.gr
Site Name
Thoracic General Hospital Of Athens I Sotiria
Department Name
3rd Department of Internal Medicine
Principal Investigator Name
Garifalia Poulakou
Principal Investigator Email
gpoulakou@gmail.com
Contact Person Name
Garifalia Poulakou
Contact Person Email
gpoulakou@gmail.com
Site Name
Sismanogleio General Hospital
Department Name
Intensive Care Unit
Principal Investigator Name
Aikaterini Sakagianni
Principal Investigator Email
sakagianni@sismanoglio.gr
Contact Person Name
Aikaterini Sakagianni
Contact Person Email
sakagianni@sismanoglio.gr
Site Name
Alexandra Hospital
Department Name
Ηigh Dependency Unit of Department of Clinical Therapeutics
Principal Investigator Name
Georgios Dimopoulos
Principal Investigator Email
gdimop@med.uoa.gr
Contact Person Name
Georgios Dimopoulos
Contact Person Email
gdimop@med.uoa.gr
Site Name
University General Hospital Of Thessaloniki Ahepa
Department Name
Department of Anesthesiology and Intensive Care
Principal Investigator Name
Eleni Argyriadou
Principal Investigator Email
argiriadouhelena@hotmail.gr
Contact Person Name
Eleni Argyriadou
Contact Person Email
argiriadouhelena@hotmail.gr
Site Name
General Oncological Hospital Of Kifissia Agioi Anargyroi
Department Name
Clinic of Intensive Care and Pulmonary Diseases
Principal Investigator Name
Pavlos Myrianthefs
Principal Investigator Email
pmiriant@nurs.uoa.gr
Contact Person Name
Pavlos Myrianthefs
Contact Person Email
pmiriant@nurs.uoa.gr

Sponsor

Primary sponsor

Full Name
Hellenic Institute For The Study Of Sepsis
Organisation Type
Laboratory/Research/Testing facility
Country Of Registered Address
Greece

Investigational products

Investigational Product Name
EMAPALUMAB
Active Substance
EMAPALUMAB
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
No marketing authorisation number recorded
Orphan Designation
Yes
Maximum Dose
Max daily 10 mg/kg; max total 37 mg/kg
Investigational Product Name
Sodium Chloride Injection/ DEMO 0,9% w/v
Active Substance
SODIUM CHLORIDE
Modality
Small molecule
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation: 24901/09 (Greece)
Maximum Dose
Max daily 250 ml; max total 2250 ml

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