Emapalumab Treatment For Anticipated Clinical Benefit In... | NCT06694701

ID	Type	Description	Link
2024-515255-38-00	EU Trial (CTIS) Number

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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

Name	Type	Description	Arm Group Labels	Other Names
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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Measure	Description	Time Frame
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.	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.

Other Outcomes

Measure	Description	Time Frame
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

Eligibility Module

Eligibility 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

ID	Term
D018805	Sepsis
D007239	Infections

ID	Term
D018746	Systemic Inflammatory Response Syndrome
D007249	Inflammation
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms