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

Phase 2

Completed

• Conditions: Pseudomonas Aeruginosa Infection
• Interventions: Biological: IC43; Drug: Placebo

• Registration Number: NCT01563263
• Lead Sponsor: Valneva Austria GmbH

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.

Study Timeline

• Study Start: 2012-03
• Study First Submitted: 2012-03-14
• Study First Submitted QC: 2012-03-22
• Study First Posted: 2012-03-26
• Primary Completion: 2015-08
• Study Completion: 2015-12
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-29
• Last Update Posted: 2016-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 803

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IC43 100 mcg	IC43	IC43 100 mcg intramuscular injection, IC43 is a recombinant Pseudomonas aeruginosa fusion protein
Placebo	Placebo	phosphate buffered saline solution containing 0,9 % NaCL

Primary Outcome Measures

Name	Time	Method
number of deaths until Day 28	until Day 28

Secondary Outcome Measures

Name	Time	Method
number of deaths on Day 14, 28, 56 and 90 in patients surviving Day 3 and receiving IC43 or placebo	until Day 90
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
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
number of deaths in comparison on Day 14, 56 and 90	until Day 90
number of overall survival in all patients and in patients surviving Day 14	until Day 180
Composite measure of laboratory parameters	until Day 56
Number of SAEs and AEs during the vaccination period up to 180 days after the first vaccination	until Day 180
number of local reactions at the injection site	until Day 180
number of deaths onDay 28, 56 and 90 in patients surviving Day 14 and receiving IC43 or placebo	until Day 90
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
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
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
systemic tolerability	until Day 7	body temperature

Trial Locations

Locations (50)

Faculty Hospital Kralovske Vinohrady; 🇨🇿 Prague, Czech Republic

HELIOS Klinikum Wuppertal; 🇩🇪 Wuppertal, Germany

University of Pecs; 🇭🇺 Pecs, Hungary

Vall d'Hebron University Hospital; 🇪🇸 Barcelona, Spain

University Hospital Marques de Valdecilla; 🇪🇸 Santander Cantabria, Spain

Hospital Universitario de Getafe; 🇪🇸 Madrid, Spain

LKH Salzburg; 🇦🇹 Salzburg, Austria

Kenezy Korhaz Debrecen; 🇭🇺 Debrecen, Hungary

ULB Hospital Erasme; 🇧🇪 Brussels, Belgium

Krajská nemocnice T. Bati, a.s.; 🇨🇿 Zlín, Czech Republic

University Hospital Brussels; 🇧🇪 Brussels, Belgium

Ziekenhuis Oost Limburg; 🇧🇪 Genk, Belgium

Medical University of Vienna; 🇦🇹 Vienna, Austria

Pécsi Tudományegyetem Neurológiai Klinika; 🇭🇺 Pécs, Hungary

University Hospital Ghent; 🇧🇪 Ghent, Belgium

Faculty Hospital; 🇨🇿 Hradec Krakove, Czech Republic

St. Imre Hospital; 🇭🇺 Budapest, Hungary

University of Szeged; 🇭🇺 Szeged, Hungary

LKH - University Clinic Graz; 🇦🇹 Graz, Austria

Krankenhaus Hietzing; 🇦🇹 Vienna, Austria

Otto Wagner Spital; 🇦🇹 Vienna, Austria

Wilhelminenspital & Kaiserin-Elisabeth-Spital; 🇦🇹 Vienna, Austria

Hospital Saint Luc; 🇧🇪 Brussels, Belgium

Clinique St. Pierre; 🇧🇪 Ottignies, Belgium

Faculty Hospital St. Ann; 🇨🇿 Brno, Czech Republic

Fakultní nemocnice Olomouc; 🇨🇿 Olomouc, Czech Republic

Faculty Hospital Motol; 🇨🇿 Prague, Czech Republic

HELIOS Klinikum Aue; 🇩🇪 Aue, Germany

Central Military Hospital; 🇨🇿 Praha, Czech Republic

HELIOS Klinikum Berlin-Buch; 🇩🇪 Berlin, Germany

Charite-Universitätsmedizin Berlin; 🇩🇪 Berlin, Germany

Carl-Thiem-Klinikum Cottbus; 🇩🇪 Cottbus, Germany

HELIOS Klinikum Erfurt; 🇩🇪 Erfurt, Germany

Städtisches Klinikum Dessau; 🇩🇪 Dessau-Roßlau, Germany

Neurologische Universitätsklinik; 🇩🇪 Dresden, Germany

Klinikum Dortmund; 🇩🇪 Dortmund, Germany

Helios Kreikrankenhaus Gotha/Ohrdruf; 🇩🇪 Gotha, Germany

Saarland University Hospital; 🇩🇪 Homburg/Saar, Germany

Bermannstrost BG Kliniken Halle; 🇩🇪 Halle/Saale, Germany

Universitätsklinikum Schleswig-Holstein; 🇩🇪 Kiel, Germany

Klinikum rechts der Isar; 🇩🇪 München, Germany

Országos Korányi TBC és Pulmonológiai Intézet; 🇭🇺 Budapest, Hungary

Debreceni Egyetem OEC Kazincbarcikai Korhaz; 🇭🇺 Kazincbarcika, Hungary

Uzsoki Hospital; 🇭🇺 Budapest, Hungary

Flor Ferenc Korhaz Hospital; 🇭🇺 Kistarcsa, Hungary

Fejer County Hospital; 🇭🇺 Szekesfehervar, Hungary

Hospital Universitario Infanta Cristina; 🇪🇸 Badajoz, Spain

Hospital Universitario Dr. Peset; 🇪🇸 Valencia, Spain

Hospital Universitario y Policlínico La Fe; 🇪🇸 Valencia, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain