Effort to Prevent Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa in Mechanically Ventilated Subjects (EVADE)

A Phase 2 Proof-of-concept Study to Evaluate the Efficacy and Safety of MEDI3902 in Mechanically Ventilated Patients for the Prevention of Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa

Clinical trial looking to evaluate the efficacy and safety of MEDI3902 in mechanically ventilated participants for the prevention of nosocomial pneumonia caused by Pseudomonas aeruginosa.

Study Overview

• Status: Completed
• Conditions: Pseudomonas Aeruginosa
• Intervention / Treatment: Drug: MEDI3902; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 188
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Research Site
  • Wien, Austria, 1080
    • Research Site
• Belgium
  • Bruges, Belgium, 8000
    • Research Site
  • Brussels, Belgium, 1090
    • Research Site
  • Brussels, Belgium, 1020
    • Research Site
  • Genk, Belgium, 3600
    • Research Site
  • Gent, Belgium, 9000
    • Research Site
  • Haine-Saint-Paul, Belgium, 7100
    • Research Site
  • Ottignies, Belgium, 1340
    • Research Site
• Croatia
  • Slavonski Brod, Croatia, 35000
    • Research Site
• Czechia
  • Brno, Czechia, 656 91
    • Research Site
  • Decin, Czechia, 405 99
    • Research Site
  • Kolin, Czechia, 280 02
    • Research Site
  • Kyjov, Czechia, 697 01
    • Research Site
  • Teplice, Czechia, 415 29
    • Research Site
• France
  • Argenteuil, France, 95107
    • Research Site
  • Clermont-ferrand, France, 63003
    • Research Site
  • Garches, France, 92380
    • Research Site
  • La Tronche, France, 38700
    • Research Site
  • Le Kremlin Bicetre, France, 94275
    • Research Site
  • Le Plessis Robinson, France, 92350
    • Research Site
  • Lille Cedex, France, 59037
    • Research Site
  • Limoges, France, 87042
    • Research Site
  • Montpellier Cedex 5, France, 34295
    • Research Site
  • Nancy, France, 54035
    • Research Site
  • Paris, France, 75015
    • Research Site
  • Paris, France, 75679
    • Research Site
  • Paris, France, 75651
    • Research Site
  • Paris Cedex 14, France, 75014
    • Research Site
  • Pierre Benite, France, 69495
    • Research Site
  • Strasbourg, France, 67090
    • Research Site
  • Tours, France, 37000
    • Research Site
• Greece
  • Athens, Greece, 11527
    • Research Site
  • Athens, Greece, 14564
    • Research Site
  • Athens, Greece, 14233
    • Research Site
  • Athens, Greece, 10676
    • Research Site
  • Athens, Greece, 11521
    • Research Site
  • Larissa, Greece, 41110
    • Research Site
  • Larissa, Greece, 41221
    • Research Site
  • Thessaloniki, Greece, 54634
    • Research Site
• Hungary
  • Budapest, Hungary, 1121
    • Research Site
  • Kistarcsa, Hungary, 02143
    • Research Site
  • Vác, Hungary, 2600
    • Research Site
• Ireland
  • Dublin, Ireland, 6
    • Research Site
• Israel
  • Jerusalem, Israel, 91120
    • Research Site
  • Petach-Tikva, Israel, 4941492
    • Research Site
  • Ramat Gan, Israel, 5265601
    • Research Site
  • Tel Aviv, Israel, 6423906
    • Research Site
• Portugal
  • Almada, Portugal, 2805-267
    • Research Site
  • Lisboa, Portugal, 1649-035
    • Research Site
  • Lisboa, Portugal, 1449-005
    • Research Site
  • Viana do Castelo, Portugal, 4904-858
    • Research Site
• Spain
  • Barcelona, Spain, 08036
    • Research Site
  • Barcelona, Spain, 08025
    • Research Site
  • Cordoba, Spain, 14004
    • Research Site
  • Getafe, Spain, 28905
    • Research Site
  • Madrid, Spain, 28040
    • Research Site
  • Oviedo, Spain, 33011
    • Research Site
  • San Sebastián de los Reyes, Spain, 28702
    • Research Site
  • Santander, Spain, 39008
    • Research Site
  • Tarragona, Spain, 43007
    • Research Site
  • Terrassa, Spain, 08221
    • Research Site
  • Valencia, Spain, 46026
    • Research Site
  • Valladolid, Spain, 47012
    • Research Site
• Turkey
  • Ankara, Turkey, 6100
    • Research Site
  • Istanbul, Turkey, 34890
    • Research Site
  • Trabzon, Turkey, 61080
    • Research Site
• United Kingdom
  • Edgbaston, United Kingdom, B15 2GW
    • Research Site
  • London, United Kingdom, SE5 9RS
    • Research Site
  • London, United Kingdom, SE1 7EH
    • Research Site
• United States
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Research Site
  • Florida
    • Gainesville, Florida, United States, 32608
      • Research Site
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Research Site
    • Augusta, Georgia, United States, 30912
      • Research Site
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Research Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Research Site
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Colonized with P aeruginosa, expected to require prolonged intubation and mechanical ventilation, without any evidence of active pneumonia.

Exclusion Criteria:

P aeruginosa disease at randomisation; lung injury score consistent with pneumonia; current lung disease; currently receiving protocol-specified Anti-P aeruginosa antibiotics, moribund participants.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MEDI3902 500 mg; Participants will receive a single intravenous (IV) dose of 500 mg MEDI3902.	Drug: MEDI3902; Participants will receive a single IV dose of MEDI3902 500 mg and 1500 mg in MEDI3902 500 mg arm and MEDI3902 1500 mg arm, respectively.
PLACEBO_COMPARATOR: Placebo; Participants will receive a single IV dose of placebo matched to MEDI3902.	Other: Placebo; Participants will receive a single IV dose of placebo matched to MEDI3902.
EXPERIMENTAL: MEDI3902 1500 mg; Participants will receive a single IV dose of 1500 mg MEDI3902.	Drug: MEDI3902; Participants will receive a single IV dose of MEDI3902 500 mg and 1500 mg in MEDI3902 500 mg arm and MEDI3902 1500 mg arm, respectively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa	Percentage of participants with nosocomial pneumonia caused by Pseudomonas aeruginosa is reported.	Day 1 through Day 22
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.	Day 1 through Day 50
Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs)	An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.	Day 1 through Day 50
Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI)	An AESI is one of scientific and medical interest specific event for understanding of the study drug and may require close monitoring and rapid communication by the investigator to the sponsor. An AESI may be serious or non-serious.	Day 1 through Day 50

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Concentration (Cmax) of MEDI3902	The Cmax of MEDI3902 is reported.	Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3902	The AUC0-inf of MEDI3902 is reported.	Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Clearance (CL) of MEDI3902	The CL of MEDI3902 from body after intrevanous administration of single dose is reported.	Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Percentage of Participants Maintaining MEDI3902 Serum Levels Above the Target Level (1.7 µg/mL) Through 21 Days Post Dose	Percentage of participants maintaining MEDI3902 serum levels above the target level (1.7 µg/mL) through 21 days post dose is reported.	Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, and Day 22
Terminal Elimination Half-life (t1/2) of MEDI3902	The t1/2 of MEDI3902 is reported.	Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50
Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment	Number of participants with positive ADA to MEDI3902 treatment is reported. Persistent positive is defined as positive at >= 2 post-baseline assessments or positive at last post-baseline assessment. Transient positive is defined as negative at last post-baseline assessment and positive at only one post-baseline assessment or at >= 2 post-baseline assessments.	Day 1 (predose), Day 15, Day 29, Day 50

Collaborators and Investigators

• Sponsor: MedImmune LLC
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Antibacterial Resistance Leadership Group; INNOVATIVE MEDICINES INITIATIVE and COMBACTE-MAGNET

Publications and helpful links

General Publications

• Chastre J, Francois B, Bourgeois M, Komnos A, Ferrer R, Rahav G, De Schryver N, Lepape A, Koksal I, Luyt CE, Sanchez-Garcia M, Torres A, Eggimann P, Koulenti D, Holland TL, Ali O, Shoemaker K, Ren P, Sauser J, Ruzin A, Tabor DE, Akhgar A, Wu Y, Jiang Y, DiGiandomenico A, Colbert S, Vandamme D, Coenjaerts F, Malhotra-Kumar S, Timbermont L, Oliver A, Barraud O, Bellamy T, Bonten M, Goossens H, Reisner C, Esser MT, Jafri HS; COMBACTE-MAGNET EVADE Study Group. Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial. Crit Care. 2022 Nov 15;26(1):355. doi: 10.1186/s13054-022-04204-9.

Helpful Links

• Redacted CSP for CT.gov results
• D5470C00004 Redacted SAP for CT.gov results

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 25, 2016
• Primary Completion (ACTUAL): December 4, 2019
• Study Completion (ACTUAL): December 4, 2019

Study Registration Dates

• First Submitted: February 11, 2016
• First Submitted That Met QC Criteria: February 25, 2016
• First Posted (ESTIMATE): March 2, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 4, 2021
• Last Update Submitted That Met QC Criteria: January 19, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Pseudomonas aeruginosa, Pneumonia
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pseudomonas Infections
• Other Study ID Numbers: D5470C00004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes