Novel nebulized phage cocktail in CF patients with chronic P. aeruginosa pulmonary infection: a Ph1b/2a randomized, double-blind, placebo-controlled trial

Le résumé fourni par la source

Objectives: Pseudomonas aeruginosa (PsA) causes pulmonary infections in cystic fibrosis (CF) patients, despite use of elexacaftor/tezacaftor/ivacaftor (ETI). This study assessed the safety and efficacy of BX004-A (phage cocktail) in CF subjects with chronic PsA pulmonary infection. Methods: This Ph1b/2a randomized, double-blind, placebo-controlled, multicenter trial assessed nebulized BX004-A in 43 adult CF subjects with FEV1≥40% and chronic PsA pulmonary infection, on inhaled antibiotics. In Part 1 (n=9), subjects were randomized (3:1) to BX004-A or placebo x7d. In Part 2 (n=34), subjects were randomized (2:1) to twice daily BX004-A or placebo x10d. Results: In Part 1, the mean sputum PsA colony forming unit (CFU/g) reduction at D15 (vs baseline) was -1.42 log (BX004-A) vs -0.28 log (placebo). In Part 2, in subjects with quantitative sputum PsA CFU at baseline, 3/21 (14.3%) on BX004-A had a negative PsA sputum culture at D10 vs 0/10 (0%) on placebo. In subjects on continuous inhaled antibiotics (rather than cycling/alternating), on ETI and with FEV1 <70%, mean sputum PsA CFU reduction at D10 was -3.84 log (BX004-A) vs -1.03 log (placebo), with a relative FEV1 of +8.89% at D17 between groups (change from baseline +5.66% in BX004-A vs -3.23% in placebo). Phage was detected in the sputum of all subjects on BX004-A, with no treatment-related phage resistance. During therapy, there were no adverse events of special interest or serious adverse events. Conclusions: BX004-A showed favorable safety and notable microbiologic and clinical efficacy. Next study will assess longer treatment.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.