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

• ClinicalTrials.gov Identifier: NCT02696902
• Recruitment Status: Completed
• First Posted: March 2, 2016
• Results First Posted: December 23, 2020
• Last Update Posted: February 4, 2021
• Sponsor: MedImmune LLC
• Collaborators: INNOVATIVE MEDICINES INITIATIVE and COMBACTE-MAGNET; Antibacterial Resistance Leadership Group; National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by (Responsible Party): MedImmune LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pseudomonas Aeruginosa	Drug: MEDI3902; Other: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 188 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: March 25, 2016
• Actual Primary Completion Date: December 4, 2019
• Actual Study Completion Date: December 4, 2019

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Nosocomial Pneumonia Caused by Pseudomonas Aeruginosa [ Time Frame: Day 1 through Day 22 ]
   Percentage of participants with nosocomial pneumonia caused by Pseudomonas aeruginosa is reported.
2. Number of Participants With Treatment-emergent Adverse Events (TEAEs) [ Time Frame: Day 1 through Day 50 ]
   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.
3. Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: Day 1 through Day 50 ]
   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.
4. Number of Participants With Treatment-emergent Adverse Events of Special Interest (TEAESI) [ Time Frame: Day 1 through Day 50 ]
   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.

Secondary Outcome Measures :

1. Maximum Observed Concentration (Cmax) of MEDI3902 [ Time Frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 ]
   The Cmax of MEDI3902 is reported.
2. Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of MEDI3902 [ Time Frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 ]
   The AUC0-inf of MEDI3902 is reported.
3. Clearance (CL) of MEDI3902 [ Time Frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 ]
   The CL of MEDI3902 from body after intrevanous administration of single dose is reported.
4. Percentage of Participants Maintaining MEDI3902 Serum Levels Above the Target Level (1.7 µg/mL) Through 21 Days Post Dose [ Time Frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, and Day 22 ]
   Percentage of participants maintaining MEDI3902 serum levels above the target level (1.7 µg/mL) through 21 days post dose is reported.
5. Terminal Elimination Half-life (t1/2) of MEDI3902 [ Time Frame: Day 1 (predose; 0 and 8 hours post dose), Day 2, Day 4, Day 8, Day 15, Day 22, Day 29, and Day 50 ]
   The t1/2 of MEDI3902 is reported.
6. Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI3902 Treatment [ Time Frame: Day 1 (predose), Day 15, Day 29, Day 50 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 99 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Colorado

Research Site

Englewood, Colorado, United States, 80113

United States, Florida

Research Site

Gainesville, Florida, United States, 32608

United States, Georgia

Research Site

Atlanta, Georgia, United States, 30322

Research Site

Augusta, Georgia, United States, 30912

United States, Maryland

Research Site

Annapolis, Maryland, United States, 21401

United States, Massachusetts

Research Site

Boston, Massachusetts, United States, 02111

United States, Michigan

Research Site

Detroit, Michigan, United States, 48202

United States, Ohio

Research Site

Cincinnati, Ohio, United States, 45267

Austria

Research Site

Innsbruck, Austria, 6020

Research Site

Wien, Austria, 1080

Belgium

Research Site

Bruges, Belgium, 8000

Research Site

Brussels, Belgium, 1020

Research Site

Brussels, Belgium, 1090

Research Site

Genk, Belgium, 3600

Research Site

Gent, Belgium, 9000

Research Site

Haine-Saint-Paul, Belgium, 7100

Research Site

Ottignies, Belgium, 1340

Croatia

Research Site

Slavonski Brod, Croatia, 35000

Czechia

Research Site

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

France

Research Site

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 Cedex 14, France, 75014

Research Site

Paris, France, 75015

Research Site

Paris, France, 75651

Research Site

Paris, France, 75679

Research Site

Pierre Benite, France, 69495

Research Site

Strasbourg, France, 67090

Research Site

Tours, France, 37000

Greece

Research Site

Athens, Greece, 10676

Research Site

Athens, Greece, 11521

Research Site

Athens, Greece, 11527

Research Site

Athens, Greece, 14233

Research Site

Athens, Greece, 14564

Research Site

Larissa, Greece, 41110

Research Site

Larissa, Greece, 41221

Research Site

Thessaloniki, Greece, 54634

Hungary

Research Site

Budapest, Hungary, 1121

Research Site

Kistarcsa, Hungary, 02143

Research Site

Vác, Hungary, 2600

Ireland

Research Site

Dublin, Ireland, 6

Israel

Research Site

Jerusalem, Israel, 91120

Research Site

Petach-Tikva, Israel, 4941492

Research Site

Ramat Gan, Israel, 5265601

Research Site

Tel Aviv, Israel, 6423906

Portugal

Research Site

Almada, Portugal, 2805-267

Research Site

Lisboa, Portugal, 1449-005

Research Site

Lisboa, Portugal, 1649-035

Research Site

Viana do Castelo, Portugal, 4904-858

Spain

Research Site

Barcelona, Spain, 08025

Research Site

Barcelona, Spain, 08036

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

Turkey

Research Site

Ankara, Turkey, 6100

Research Site

Istanbul, Turkey, 34890

Research Site

Trabzon, Turkey, 61080

United Kingdom

Research Site

Edgbaston, United Kingdom, B15 2GW

Research Site

London, United Kingdom, SE1 7EH

Research Site

London, United Kingdom, SE5 9RS

Sponsors and Collaborators

MedImmune LLC

INNOVATIVE MEDICINES INITIATIVE and COMBACTE-MAGNET

Antibacterial Resistance Leadership Group

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Director: MedImmune LLC; MedImmune LLC

  Study Documents (Full-Text)

Documents provided by MedImmune LLC:

Study Protocol  [PDF] June 6, 2018

Statistical Analysis Plan  [PDF] February 17, 2020

More Information

Additional Information:

Redacted CSP for CT.gov results 

D5470C00004 Redacted SAP for CT.gov results 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: MedImmune LLC
• ClinicalTrials.gov Identifier: NCT02696902
• Other Study ID Numbers: D5470C00004
• First Posted: March 2, 2016
• Results First Posted: December 23, 2020
• Last Update Posted: February 4, 2021
• Last Verified: January 2021

• 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

Keywords provided by MedImmune LLC:

Pseudomonas aeruginosa, Pneumonia

Additional relevant MeSH terms:

Pneumonia; Pseudomonas Infections; Healthcare-Associated Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes