Confirmatory Phase II/III Study Assessing Efficacy, Immunogenicity and Safety of IC43

• number of deaths in comparison on Day 14, 56 and 90 [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of deaths onDay 28, 56 and 90 in patients surviving Day 14 and receiving IC43 or placebo [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of deaths on Day 14, 28, 56 and 90 in patients surviving Day 3 and receiving IC43 or placebo [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of overall survival in all patients and in patients surviving Day 14 [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• number of deaths related to sepsis at Day 14, 28, 56 and 90 in patients receiving IC43 or placebo [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of surviving subjects after Sepsis receiving IC43 or placebo [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• number of deaths in patients in-ICU and in-hospital receiving IC43 or placebo until Day 14, 28, 56,90, 180 [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• percentage of patients with invasive infection with P. aeruginosa, such as bacteremia or P. aeruginosa urinary tract infection in patients receiving IC43 or placebo up to Day 56 after first vaccination [ Time Frame: until Day 56 ] [ Designated as safety issue: No ]
• percentage of patients with P. aeruginosa respiratory tract infection or P. aeruginosa respiratory tract colonization in patients receiving IC43 or placebo up to Day 56 after first vaccination [ Time Frame: until Day 56 ] [ Designated as safety issue: No ]
• Organ function in patients receiving IC43 or placebo during ICU stay [ Time Frame: during ICU stay ] [ Designated as safety issue: No ]
• Days of ICU stay in patients receiving IC43 or placebo [ Time Frame: Until Day 180 ] [ Designated as safety issue: No ]
• Immunogenicity at Day 7, 14, 28, 56 and 180 as determined by OprF/I specific IgG antibody titer measured by ELISA in patients receiving IC43 or placebo [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• Number of SAEs and AEs during the vaccination period up to 180 days after the first vaccination [ Time Frame: until Day 180 ] [ Designated as safety issue: Yes ]
• systemic tolerability [ Time Frame: until Day 7 ] [ Designated as safety issue: Yes ]
  blood pressure
• number of local reactions at the injection site [ Time Frame: until Day 180 ] [ Designated as safety issue: Yes ]
• safety laboratory parameters [ Time Frame: until Day 56 ] [ Designated as safety issue: Yes ]
• systemic tolerability [ Time Frame: until Day 7 ] [ Designated as safety issue: Yes ]
  pulse
• systemic tolerability [ Time Frame: until Day 7 ] [ Designated as safety issue: Yes ]
  body temperature

• number of deaths in comparison on Day 14, 56 and 90 [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of deaths onDay 28, 56 and 90 in patients surviving Day 14 and receiving IC43 or placebo [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of deaths on Day 14, 28, 56 and 90 in patients surviving Day 3 and receiving IC43 or placebo [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of overall survival in all patients and in patients surviving Day 14 [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• number of deaths related to sepsis at Day 14, 28, 56 and 90 in patients receiving IC43 or placebo [ Time Frame: until Day 90 ] [ Designated as safety issue: No ]
• number of surviving subjects after Sepsis receiving IC43 or placebo [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• number of deaths in patients in-ICU and in-hospital receiving IC43 or placebo until Day 14, 28, 56,90, 180 [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• percentage of patients with invasive infection with P. aeruginosa, such as bacteremia or P. aeruginosa urinary tract infection in patients receiving IC43 or placebo up to Day 56 after first vaccination [ Time Frame: until Day 56 ] [ Designated as safety issue: No ]
• percentage of patients with P. aeruginosa respiratory tract infection or P. aeruginosa respiratory tract colonization in patients receiving IC43 or placebo up to Day 56 after first vaccination [ Time Frame: until Day 56 ] [ Designated as safety issue: No ]
• Organ function in patients receiving IC43 or placebo during ICU stay [ Time Frame: during ICU stay ] [ Designated as safety issue: No ]
• Days of ICU stay in patients receiving IC43 or placebo [ Time Frame: Until Day 180 ] [ Designated as safety issue: No ]
• Immunogenicity at Day 7, 14, 28, 56 and 180 as determined by OprF/I specific IgG antibody titer measured by ELISA in patients receiving IC43 or placebo [ Time Frame: until Day 180 ] [ Designated as safety issue: No ]
• Number of SAEs and AEs during the vaccination period up to 180 days after the first vaccination [ Time Frame: until Day 180 ] [ Designated as safety issue: Yes ]
• systemic tolerability (blood pressure in mmHg, pulse in bpm, body temperature in °C) [ Time Frame: until Day 7 ] [ Designated as safety issue: Yes ]
  blood pressure, pulse, body temperature
• number of local reactions at the injection site [ Time Frame: until Day 180 ] [ Designated as safety issue: Yes ]
• safety laboratory parameters (unit depends on parameter) [ Time Frame: until Day 56 ] [ Designated as safety issue: Yes ]
  hematology: Hemoglobin, hematocrit, erythrocyte count, white blood count, platelets Chemistry: creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), c-reactive protein (CRP)

This is a confirmatory, randomized, placebo-controlled, multi-center, double-blinded phase II/III study. The study population consists of male or female ICU patients with a need for mechanical ventilation for more than 48 hours, aged between 18 and 80 years.

This is a confirmatory, randomized, placebo-controlled, multi-center, double-blinded phase II/III study. The study population consists of male or female ICU patients with a need for mechanical ventilation for more than 48 hours, aged between 18 and 80 years.

Eight-hundred patients will be enrolled at approximately 50 study centers. Informed consent (i.e., from the patient or from the patient's legally authorized representative) or waiver will be obtained according to regional requirements prior to any study related procedures. Patients will be randomized to receive either IC43 100 mcg or placebo and will receive the first vaccination on Day 0. The second vaccination will be applied on Day 7. In case ICU discharge occurs before Day 7, immunization will be done at the hospital ward.

• Biological: IC43
  100 mcg
  Other Name: Pseudomonas Aeruginosa
• Drug: Placebo
  phosphate buffered saline (PBS) solution containing 0,9 % NaCl
  Other Name: phosphate buffered saline (PBS)

• Active Comparator: IC43 100 mcg
  IC43 100 mcg intramuscular injection, IC43 is a recombinant Pseudomonas aeruginosa fusion protein
  Intervention: Biological: IC43
• Placebo Comparator: Placebo
  phosphate buffered saline solution containing 0,9 % NaCL
  Intervention: Drug: Placebo

Inclusion Criteria:

• male or female patients admitted to an ICU with need for mechanical ventilation for at least 48 hours, aged between 18 and 80 years at Visit 0
• written informed consent or waiver according to the national regulations
• no childbearing potential or negative pregnancy test

Exclusion Criteria:

• SOFA < 4 on Day 0
• Patients <6 months post organ transplantation
• readmission to ICU during the current total hospital stay on Day 0
• patients admitted to ICU within 2 days after surgery
• patients admitted to ICU due to trauma
• elective surgery until Day 28 after first vaccination