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

Jean Chastre, Bruno François, Marc Bourgeois, Apostolos Komnos, Ricard Ferrer, Galia Rahav, Nicolas De Schryver, Alain Lepape, Iftihar Koksal, Charles-Edouard Luyt, Miguel Sánchez-García, Antoni Torres, Philippe Eggimann, Despoina Koulenti, Thomas L. Holland, Omar Ali, Kathryn Shoemaker, Pin Ren, Julien Sauser, Alexey RuzinDavid E. Tabor, Ahmad Akhgar, Yuling Wu, Yu Jiang, Antonio DiGiandomenico, Susan Colbert, Drieke Vandamme, Frank Coenjaerts, Surbhi Malhotra-Kumar, Leen Timbermont, Antonio Oliver, Olivier Barraud, Terramika Bellamy, Marc Bonten, Herman Goossens, Colin Reisner, Mark T. Esser, Hasan S. Jafri, Michael Joannidis, Walter Klimscha, Elisabeth De Waele, Jacques Devriendt, Vincent Huberlant, Pieter Depuydt, Sam Van Boxstael, Mladen Peric, Jasminka Kopic, Michal Hanauer, Tomas Hruby, Vladimir Sramek, Petr Svoboda, Tomas Vymazal, Martin Novacek, Djillali Annane, Jean-Paul Mira, Bertrand Souweine, Pierre-François Dequin, Ferhat Meziani, François Stephan, Saad Nseir, Sebastien Gibot, Carole Schwebel, Gaetan Plantefeve, Jean-Luc Diehl, Christian Richard, Christian Lamer, Kada Klouche, Samir Jaber, Epaminondas Zakynthinos, Georgios Filntisis, Spyros Zakynthinos, Antonia Koutsoukou, Georgios Saroglou, Charikleia Nikolaou, Glykeria Vlachogianni, Ioannis Pnevmatikos, Konstantinos Mandragos, Ildiko Kremer, Zsolt Dezso Rozgonyi, Zsuzsa Marjanek, Ignacio Martin-Loeches, Pierre Singer, Vernon Van Heerden, Yehuda Carmeli, Pedro Povoa, Antonio AlvarezSeoane, Pedro Moura, Filipe Gonzalez, Paula Ramirez, Antonio Torres Marti, Lorena Oteiza, Dolores Escudero, Enrique Piacentini, Paula Vera-Artazcoz, Luis Tamayo, Miguel Angel Gonzalez Gallego, Borja Suberviola Canas, Iglesias Figueira, Rafael Leon, Volkan Korten, Murat Akova, Duncan Wyncoll, Tony Whitehouse, Phil Hopkins, Malcolm Sim, Yoav Golan, Marcus Zervos, Jose Vazquez, Kartikeya Cherabuddi, George Smulian, Nadine Rouphael, James Welker, Mathew Sims, David Van Duin, Todd McCarthy, Christopher Polk

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Background: Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomial pneumonia was assessed in PA-colonised mechanically ventilated subjects. Methods: EVADE (NCT02696902) was a phase 2, randomised, parallel-group, double-blind, placebo-controlled study in Europe, Turkey, Israel, and the USA. Subjects ≥ 18 years old, mechanically ventilated, tracheally colonised with PA, and without new-onset pneumonia, were randomised (1:1:1) to MEDI3902 500, 1500 mg (single intravenous dose), or placebo. The primary efficacy endpoint was the incidence of nosocomial PA pneumonia through 21 days post-dose in MEDI3902 1500 mg versus placebo, determined by an independent adjudication committee. Results: Even if the initial sample size was not reached because of low recruitment, 188 subjects were randomised (MEDI3902 500/1500 mg: n = 16/87; placebo: n = 85) between 13 April 2016 and 17 October 2019. Out of these, 184 were dosed (MEDI3902 500/1500 mg: n = 16/85; placebo: n = 83), comprising the modified intent-to-treat set. Enrolment in the 500 mg arm was discontinued due to pharmacokinetic data demonstrating low MEDI3902 serum concentrations. Subsequently, enrolled subjects were randomised (1:1) to MEDI3902 1500 mg or placebo. PA pneumonia was confirmed in 22.4% (n = 19/85) of MEDI3902 1500 mg recipients and in 18.1% (n = 15/83) of placebo recipients (relative risk reduction [RRR]: − 23.7%; 80% confidence interval [CI] − 83.8%, 16.8%; p = 0.49). At 21 days post-1500 mg dose, the mean (standard deviation) serum MEDI3902 concentration was 9.46 (7.91) μg/mL, with 80.6% (n = 58/72) subjects achieving concentrations
Idioma originalAnglès
RevistaCritical Care
Volum26
Número1
DOIs
Estat de la publicacióPublicada - 2022

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