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

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

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.

Study Overview

• Status: Completed
• Conditions: Pseudomonas Aeruginosa Infection
• Intervention / Treatment: Biological: IC43; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 803
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8036
    • LKH - University Clinic Graz
  • Salzburg, Austria, 5050
    • LKH Salzburg
  • Vienna, Austria, 1090
    • Medical University of Vienna
  • Vienna, Austria, 1130
    • Krankenhaus Hietzing
  • Vienna, Austria, 1140
    • Otto Wagner Spital
  • Vienna, Austria, 1160
    • Wilhelminenspital & Kaiserin-Elisabeth-Spital
• Belgium
  • Brussels, Belgium, 1090
    • University Hospital Brussels
  • Brussels, Belgium, 1070
    • Ulb Hospital Erasme
  • Brussels, Belgium, 1200
    • Hospital Saint Luc
  • Genk, Belgium, 3600
    • Ziekenhuis Oost Limburg
  • Ghent, Belgium, 9000
    • University Hospital Ghent
  • Ottignies, Belgium, 1340
    • Clinique St. Pierre
• Czech Republic
  • Brno, Czech Republic, 65691
    • Faculty Hospital St. Ann
  • Hradec Krakove, Czech Republic, 50005
    • Faculty Hospital
  • Olomouc, Czech Republic
    • Fakultni nemocnice Olomouc
  • Prague, Czech Republic, 15006
    • Faculty Hospital Motol
  • Prague, Czech Republic, 10034
    • Faculty Hospital Kralovske Vinohrady
  • Praha, Czech Republic, 16902
    • Central Military Hospital
  • Zlín, Czech Republic
    • Krajská nemocnice T. Bati, a.s.
• Germany
  • Aue, Germany, 08280
    • Helios Klinikum Aue
  • Berlin, Germany, 13125
    • Helios Klinikum Berlin-Buch
  • Berlin, Germany, 13353
    • Charite-Universitatsmedizin Berlin
  • Cottbus, Germany, 03048
    • Carl-Thiem-Klinikum Cottbus
  • Dessau-Roßlau, Germany, 06847
    • Städtisches Klinikum Dessau
  • Dortmund, Germany, 44145
    • Klinikum Dortmund
  • Dresden, Germany, 01307
    • Neurologische Universitätsklinik
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Gotha, Germany, 99867
    • Helios Kreikrankenhaus Gotha/Ohrdruf
  • Halle/Saale, Germany, 06112
    • Bermannstrost BG Kliniken Halle
  • Homburg/Saar, Germany, 66421
    • Saarland University Hospital
  • Kiel, Germany, 24105
    • Universitätsklinikum Schleswig-Holstein
  • München, Germany, 81675
    • Klinikum rechts der Isar
  • Wuppertal, Germany, 42283
    • Helios Klinikum Wuppertal
• Hungary
  • Budapest, Hungary, 1115
    • St. Imre Hospital
  • Budapest, Hungary, 1122
    • Orszagos Koranyi Tbc es Pulmonologiai Intezet
  • Budapest, Hungary, 1145
    • Uzsoki Hospital
  • Debrecen, Hungary, 4043
    • Kenezy Korhaz Debrecen
  • Kazincbarcika, Hungary, 3700
    • Debreceni Egyetem OEC Kazincbarcikai Korhaz
  • Kistarcsa, Hungary, 2143
    • Flor Ferenc Korhaz Hospital
  • Pecs, Hungary, 7623
    • University of Pecs
  • Pécs, Hungary
    • Pecsi Tudomanyegyetem Neurologiai Klinika
  • Szeged, Hungary, 6725
    • University of Szeged
  • Szekesfehervar, Hungary, 8000
    • Fejer County Hospital
• Spain
  • Badajoz, Spain
    • Hospital Universitario Infanta Cristina
  • Barcelona, Spain, 08035
    • Vall D'Hebron University Hospital
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28905
    • Hospital Universitario de Getafe
  • Santander Cantabria, Spain, 39008
    • University Hospital Marqués de Valdecilla
  • Valencia, Spain, 46022
    • Hospital Universitario Dr. Peset
  • Valencia, Spain
    • Hospital Universitario y Policlínico La Fe

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Valneva Austria GmbH
• Investigators: Study Chair: Susanne Eder, Mag, Valneva Austria GmbH

Publications and helpful links

General Publications

• Adlbrecht C, Wurm R, Depuydt P, Spapen H, Lorente JA, Staudinger T, Creteur J, Zauner C, Meier-Hellmann A, Eller P, Laenen MV, Molnar Z, Varkonyi I, Schaaf B, Hejja M, Sramek V, Schneider H, Kanesa-Thasan N, Eder-Lingelbach S, Klingler A, Dubischar K, Wressnigg N, Rello J. Efficacy, immunogenicity, and safety of IC43 recombinant Pseudomonas aeruginosa vaccine in mechanically ventilated intensive care patients-a randomized clinical trial. Crit Care. 2020 Mar 4;24(1):74. doi: 10.1186/s13054-020-2792-z.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: March 14, 2012
• First Submitted That Met QC Criteria: March 22, 2012
• First Posted (Estimate): March 26, 2012

Study Record Updates

• Last Update Posted (Estimate): March 31, 2016
• Last Update Submitted That Met QC Criteria: March 29, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Pseudomonas Aeruginosa; ICU patients; IC43; mechanically ventilated ICU patients
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pseudomonas Infections
• Other Study ID Numbers: IC43-202