E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Nosocomial Pseudomonas aeruginosa infections in mechanically ventilated ICU patients |
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E.1.1.1 | Medical condition in easily understood language |
Pseudomonas aeruginosa infections in mechanically ventilated ICU patients |
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E.1.1.2 | Therapeutic area | Diseases [C] - Bacterial Infections and Mycoses [C01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061471 |
E.1.2 | Term | Pseudomonas infection |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To show the superiority of IC43 with regard to overall mortality on Day 28 after first vaccination in mechanically ventilated ICU patients. |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of IC43 on overall mortality - up to 56 and 90 days after first vaccination - on Day 14, 28, 56 and Day 90 in subjects surviving Day 3 - on Day 28 , 56 and Day 90 in subjects surviving Day 14 To investigate the effect of IC43 on - overall survival - patients with history of a hepatobiliary disorder: overall mortality on day 28 and overall survival - sepsis‐related mortality - in-hospital mortality rates To analyze the impact of IC43 on sequential organ function assessments (SOFA) compared to placebo To compare incidence rates of - invasive P. aeruginosa (P.a.) infection in ICU patients receiving IC43 vs placebo - P. a. respiratory tract infection or colonization in ICU patients receiving IC43 vs placebo To investigate the - length of ICU stay in patients receiving IC43 vs placebo - immunogenicity of IC43 in mechanically ventilated ICU patients - safety and tolerability of IC43 during a period of up to 180 days after the first vaccination |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 (e.g., by the patient or his/her legally authorized representative) or waiver according to the national regulations
No childbearing potential or negative pregnancy test |
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E.4 | Principal exclusion criteria |
SOFA < 4 on Day 0
Patients < 6 months post organ transplantation
Expected plasmapheresis or immunoadsorption
Readmission to ICU during the current total hospital stay on Day 0
Patients admitted to ICU within 48 hours after surgery or due to trauma at Day 0
Elective surgery until Day 28 after first vaccination |
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E.5 End points |
E.5.1 | Primary end point(s) |
Day 28 all cause mortality in patients receiving IC43 or placebo |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints : 1) Day 14,56 and 90 all cause mortality in patients receiving IC43 or placebo 2) Day 28, 56 and 90 all cause mortality in patients surviving Day 14 and receiving IC43 or placebo 3) Day 14, 28, 56 and 90 all cause mortality in patients surviving Day 3 and receiving IC43 or placebo 4) Overall survival in all patients and in patients surviving Day 14 5) Day 28 all cause mortality in patients with documented medical history of a hepatobiliary disorder receiving IC43 or placebo 6) Overall survival in patients with documented medical history of a hepatobiliary disorder 7) Sepsis‐related mortality at Day 14, 28, 56 and 90 in patients receiving IC43 or placebo 8) Sepsis‐related survival in patients receiving IC43 or placebo 9) In‐ICU and in‐hospital mortality in patients receiving IC43 or placebo until Day 14, 28, 56, 90, 180 10) Percentage of patients with invasive infection with P. aeruginosa, such as bacteremia (determined as positive blood culture) or P. aeruginosa urinary tract infection in patients receiving IC43 or placebo within 28 and 56, 90 and 180 days after first vaccination 11) Percentage of patients with P. aeruginosa respiratory tract infection (pneumonia or tracheobronchitis) or P. aeruginosa respiratory tract colonization in patients receiving IC43 or placebo within 28 and 56, 90 and 180 days after first vaccination 12) Organ function (Sequential Organ Failure Assessment [SOFA] scores) in patients receiving IC43 or placebo during ICU stay 13) Length of ICU stay in patients receiving IC43 or placebo
Immunogenicity endpoints: 1) 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
Safety endpoints: 1) Rate of serious adverse events and adverse events during the vaccination period up to 180 days after the first vaccination 2) Systemic tolerability (Vital signs: blood pressure, pulse, body temperature) 3) Local tolerability (local injection site reactions) 4) Safety laboratory parameters (hematology, serum chemistry) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Efficacy endpoints : 1) Day 14, 56 and 90 2) Day 28, 56 and 90 3) Day 14, 28, 56 and 90 4) Day 14 5) Day 28 6) Day 180 7) Day 14, 28, 56 and 90 8) Day 180 9) Day 14, 28, 56, 90, 180 10) Day 28, 56, 90, 180 11) Day 28, 56, 90, 180 12) Day 180 13) Day 180
Immunogenicity endpoints: 1) Day 7, 14, 28, 56 and 180
Safety endpoints: 1) 180 days 2) Day 180 3) Day 180 4) Day 180
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Mortality, Immunogenicity |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 50 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |