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

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

Detailed Description
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This is a confirmatory, randomized, placebo-controlled, multi-center, double-blinded phase II/III study. The study population consists of male or female intensive care unit (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.

Official Title
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A Confirmatory Phase II/III Study Assessing Efficacy, Immunogenicity and Safety of IC43 Recombinant Pseudomonas Vaccine Intensive Care Patients

Conditions
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Pseudomonas Aeruginosa Infection

Intervention / Treatment
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* Biological: IC43
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female patients admitted to an intensive care unit (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: Sequential Organ Failure Assessment (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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IC43 100 mcg<br>IC43 100 mcg intramuscular injection, IC43 is a recombinant Pseudomonas aeruginosa fusion protein | Biological: IC43<br>* 100 mcg<br>* Other names: Pseudomonas Aeruginosa;|
| Placebo Comparator: Placebo<br>phosphate buffered saline solution containing 0,9 % NaCL | Drug: Placebo<br>* phosphate buffered saline (PBS) solution containing 0,9 % NaCl<br>* Other names: phosphate buffered saline (PBS);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of deaths until Day 28 |  | until Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of deaths in comparison on Day 14, 56 and 90 |  | until Day 90 | 
| number of deaths onDay 28, 56 and 90 in patients surviving Day 14 and receiving IC43 or placebo |  | until Day 90 | 
| number of deaths on Day 14, 28, 56 and 90 in patients surviving Day 3 and receiving IC43 or placebo |  | until Day 90 | 
| number of overall survival in all patients and in patients surviving Day 14 |  | until Day 180 | 
| number of deaths related to sepsis at Day 14, 28, 56 and 90 in patients receiving IC43 or placebo |  | until Day 90 | 
| number of surviving subjects after Sepsis receiving IC43 or placebo |  | until Day 180 | 
| number of deaths in patients in-ICU and in-hospital receiving IC43 or placebo until Day 14, 28, 56,90, 180 |  | until Day 180 | 
| 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 |  | until Day 56 | 
| 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 |  | until Day 56 | 
| Organ function in patients receiving IC43 or placebo during ICU stay |  | during ICU stay | 
| Days of ICU stay in patients receiving IC43 or placebo |  | Until Day 180 | 
| 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 |  | until Day 180 | 
| Number of SAEs and AEs during the vaccination period up to 180 days after the first vaccination |  | until Day 180 | 
| systemic tolerability | blood pressure | until Day 7 | 
| number of local reactions at the injection site |  | until Day 180 | 
| Composite measure of laboratory parameters |  | until Day 56 | 
| systemic tolerability | pulse | until Day 7 | 
| systemic tolerability | body temperature | until Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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IC43, Pseudomonas Aeruginosa, mechanically ventilated ICU patients, ICU patients