Clinical trial NCT01563263: Confirmatory Phase II/III Study Assessing Efficacy, Immunogenicity and Safety of IC43
Official title: A Confirmatory Phase II/III Study Assessing Efficacy, Immunogenicity and Safety of IC43 Recombinant Pseudomonas Vaccine Intensive Care Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Pseudomonas Aeruginosa Infection
Keywords: IC43
Pseudomonas Aeruginosa
mechanically ventilated ICU patients
ICU patients
Lead sponsor: Valneva Austria GmbH
Sponsor class: INDUSTRY
First posted: 2012-03-26
Enrollment: 803
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: number of deaths until Day 28
timeFrame: until Day 28
Secondary outcomes:
measure: number of deaths in comparison on Day 14, 56 and 90
timeFrame: until Day 90
measure: number of deaths onDay 28, 56 and 90 in patients surviving Day 14 and receiving IC43 or placebo
timeFrame: until Day 90
measure: number of deaths on Day 14, 28, 56 and 90 in patients surviving Day 3 and receiving IC43 or placebo
timeFrame: until Day 90
measure: number of overall survival in all patients and in patients surviving Day 14
timeFrame: until Day 180
measure: number of deaths related to sepsis at Day 14, 28, 56 and 90 in patients receiving IC43 or placebo
timeFrame: until Day 90
measure: number of surviving subjects after Sepsis receiving IC43 or placebo
timeFrame: until Day 180
measure: number of deaths in patients in-ICU and in-hospital receiving IC43 or placebo until Day 14, 28, 56,90, 180
timeFrame: until Day 180
measure: 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
timeFrame: until Day 56
measure: 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
timeFrame: until Day 56
measure: Organ function in patients receiving IC43 or placebo during ICU stay
timeFrame: during ICU stay
measure: Days of ICU stay in patients receiving IC43 or placebo
timeFrame: Until Day 180
measure: 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
timeFrame: until Day 180
measure: Number of SAEs and AEs during the vaccination period up to 180 days after the first vaccination
timeFrame: until Day 180
measure: systemic tolerability
timeFrame: until Day 7
measure: number of local reactions at the injection site
timeFrame: until Day 180
measure: Composite measure of laboratory parameters
timeFrame: until Day 56
measure: systemic tolerability
timeFrame: until Day 7
measure: systemic tolerability
timeFrame: until Day 7
Other outcomes:
Locations:
city: Graz
country: Austria
facility: LKH - University Clinic Graz
city: Salzburg
country: Austria
facility: LKH Salzburg
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Vienna
country: Austria
facility: Krankenhaus Hietzing
city: Vienna
country: Austria
facility: Otto Wagner Spital
city: Vienna
country: Austria
facility: Wilhelminenspital & Kaiserin-Elisabeth-Spital
city: Brussels
country: Belgium
facility: ULB Hospital Erasme
city: Brussels
country: Belgium
facility: University Hospital Brussels
city: Brussels
country: Belgium
facility: Hospital Saint Luc
city: Genk
country: Belgium
facility: Ziekenhuis Oost Limburg
city: Ghent
country: Belgium
facility: University Hospital Ghent
city: Ottignies
country: Belgium
facility: Clinique St. Pierre
city: Brno
country: Czech Republic
facility: Faculty Hospital St. Ann
city: Hradec Krakove
country: Czech Republic
facility: Faculty Hospital
city: Olomouc
country: Czech Republic
facility: Fakultní nemocnice Olomouc
city: Prague
country: Czech Republic
facility: Faculty Hospital Kralovske Vinohrady
city: Prague
country: Czech Republic
facility: Faculty Hospital Motol
city: Praha
country: Czech Republic
facility: Central Military Hospital
city: Zlín
country: Czech Republic
facility: Krajská nemocnice T. Bati, a.s.
city: Aue
country: Germany
facility: HELIOS Klinikum Aue
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch
city: Berlin
country: Germany
facility: Charite-Universitätsmedizin Berlin
city: Cottbus
country: Germany
facility: Carl-Thiem-Klinikum Cottbus
city: Dessau-Roßlau
country: Germany
facility: Städtisches Klinikum Dessau
city: Dortmund
country: Germany
facility: Klinikum Dortmund
city: Dresden
country: Germany
facility: Neurologische Universitätsklinik
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt
city: Gotha
country: Germany
facility: Helios Kreikrankenhaus Gotha/Ohrdruf
city: Halle/Saale
country: Germany
facility: Bermannstrost BG Kliniken Halle
city: Homburg/Saar
country: Germany
facility: Saarland University Hospital
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
city: München
country: Germany
facility: Klinikum rechts der Isar
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal
city: Budapest
country: Hungary
facility: St. Imre Hospital
city: Budapest
country: Hungary
facility: Országos Korányi TBC és Pulmonológiai Intézet
city: Budapest
country: Hungary
facility: Uzsoki Hospital
city: Debrecen
country: Hungary
facility: Kenezy Korhaz Debrecen
city: Kazincbarcika
country: Hungary
facility: Debreceni Egyetem OEC Kazincbarcikai Korhaz
city: Kistarcsa
country: Hungary
facility: Flor Ferenc Korhaz Hospital
city: Pecs
country: Hungary
facility: University of Pecs
city: Pécs
country: Hungary
facility: Pécsi Tudományegyetem Neurológiai Klinika
city: Szeged
country: Hungary
facility: University of Szeged
city: Szekesfehervar
country: Hungary
facility: Fejer County Hospital
city: Badajoz
country: Spain
facility: Hospital Universitario Infanta Cristina
city: Barcelona
country: Spain
facility: Vall d'Hebron University Hospital
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario de Getafe
city: Santander Cantabria
country: Spain
facility: University Hospital Marques de Valdecilla
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Valencia
country: Spain
facility: Hospital Universitario y Policlínico La Fe
Study officials:
affiliation: Valneva Austria GmbH
name: Susanne Eder, Mag
role: STUDY_CHAIR
References:
citation: 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.