[Translation] A multicenter, randomized, double-blind, controlled phase III clinical study to evaluate the efficacy and safety of imipenem/cilastatin-XNW4107 for injection compared with imipenem/cilastatin/relebactam in the treatment of adult hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia

主要目的：评估IMI-XNW4107组与IMI/REL组相比，随机化后至D14，在MITT人群中的全因死亡率。次要目的 :1.有效性：评估IMI-XNW4107组与IMI/REL组相比，(1)随机化后至D28，在MITT人群中的全因死亡率。(2)随机化至D14和至D28，在micro-MITT，扩展micro-MITT，CE，ME和CR-MITT人群中的全因死亡率。(3)在D4，EOT，TOC和LFU时，在MITT，micro-MITT，扩展micro-MITT，CE，ME和CR-MITT人群中的临床疗效。(4)在EOT，TOC和LFU访视时，在micro-MITT，扩展的micro-MITT，ME和CR-MITT人群中的微生物学疗效。(5)在EOT，TOC和LFU访视时，在micro-MITT，扩展的micro-MITT，ME和CR-MITT人群中，按病原体分类的微生物学疗效(6)在EOT, TOC和LFU访视时，在micro-MITT，扩展的micro-MITT，ME和CR-MITT人群中的综合疗效。 2.安全性和耐受性。 3.药代动力学。探索性目的：医疗保健资源利用情况。

[Translation]

Primary Objectives: To evaluate all-cause mortality in the MITT population from randomization to D14 in the IMI-XNW4107 group compared with the IMI/REL group. Secondary Objectives: 1. Efficacy: To evaluate (1) all-cause mortality in the MITT population from randomization to D28 in the IMI-XNW4107 group compared with the IMI/REL group. (2) all-cause mortality in the micro-MITT, extended micro-MITT, CE, ME, and CR-MITT populations from randomization to D14 and to D28. (3) clinical efficacy at D4, EOT, TOC, and LFU in the MITT, micro-MITT, extended micro-MITT, CE, ME, and CR-MITT populations. (4) microbiological efficacy at the EOT, TOC, and LFU visits in the micro-MITT, extended micro-MITT, ME, and CR-MITT populations. (5) Microbiological efficacy by pathogen at EOT, TOC, and LFU visits in micro-MITT, extended micro-MITT, ME, and CR-MITT populations (6) Composite efficacy at EOT, TOC, and LFU visits in micro-MITT, extended micro-MITT, ME, and CR-MITT populations. 2. Safety and tolerability. 3. Pharmacokinetics. Exploratory objectives: Healthcare resource utilization.

Start Date31 Mar 2023

Sponsor / Collaborator

Evopoint Biosciences Co., Ltd.Startup

NCT05204368 / Not yet recruitingPhase 3

A Multicenter, Randomized, Double-Blind, Double-Dummy, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Meropenem in Hospitalized Adults With Complicated Urinary Tract Infections, Including Acute Pyelonephritis.(EudraCT no. 2022-000061-40)

This is A Multicenter, Randomized, Double-Blind, Double-Dummy, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/Funobactam in Comparison with Meropenem in Hospitalized Adults with Complicated Urinary Tract Infections, including Acute Pyelonephritis.

Start Date30 Mar 2023

Sponsor / Collaborator

Evopoint Biosciences AU Pty Ltd

NCT05204563 / RecruitingPhase 3

A Multicenter, Randomized, Double-Blind, Comparative, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Imipenem/Cilastatin/Relebactam in Adults With Hospital-Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia (EudraCT no. 2022-000081-18) (EUCTR no. 2022-501952-27-00) (IND no. 146614)

This study aims to compare treatment with Imipenem/Cilastatin-XNW4107 (IMI-XNW4107) with imipenem/cilastatin/relebactam (IMI/REL) in participants with hospital-acquired or ventilator-associated bacterial pneumonia (HABP or VAPB, respectively). The primary hypothesis is that IMI-XNW4107 is non-inferior to IMI/REL in all-cause mortality.

Start Date31 Jul 2022

Sponsor / Collaborator

Evopoint Biosciences AU Pty Ltd

100 Clinical Results associated with Funobactam

100 Translational Medicine associated with Funobactam

100 Patents (Medical) associated with Funobactam

Literatures (Medical) associated with Funobactam

05 Sep 2023·The Journal of antimicrobial chemotherapy

Imipenem/funobactam (formerly XNW4107) in vivo pharmacodynamics against serine carbapenemase-producing Gram-negative bacteria: a novel modelling approach for time-dependent killing.

Article

Author: Liu, Xiao ; Wu, Yuchuan ; Chen, Xi ; Berry, Angela V ; Abdelraouf, Kamilia ; Fratoni, Andrew J ; Nicolau, David P

BACKGROUNDImipenem/funobactam (formerly XNW4107) is a novel β-lactam/β-lactamase inhibitor with activity against MDR Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacterales strains. Using a neutropenic murine thigh infection model, we aimed to determine the pharmacokinetic/pharmacodynamic (PK/PD) index, relative to funobactam exposure, that correlated most closely with the in vivo efficacy of imipenem/funobactam combination and the magnitude of index required for efficacy against serine carbapenemase-producing clinical strains.METHODSDose-fractionation was conducted against three strains. Imipenem human-simulated regimen (HSR, 500 mg q6h 1 h infusion) efficacy in combination with escalating funobactam exposures against seven A. baumannii, four P. aeruginosa and four Klebsiella pneumoniae (imipenem/funobactam MICs 0.25-16 mg/L) was assessed as 24 h change in log10cfu/thigh.RESULTSIncreased funobactam fractionation enhanced efficacy, indicating time-dependent killing. Changes in log10cfu/thigh versus %fT > MIC were poorly predictive of efficacy; bactericidal activity was observed at %fT > MIC = 0%. Across different threshold plasma funobactam concentrations (CTs), %fT > CT(1 mg/L) had the highest correlation with efficacy. Normalizing the %fT > CT = 1 mg/L index to the respective isolate imipenem/funobactam MIC ([%fT > CT]/MIC) allowed integration of the isolate's susceptibility, which further enhanced the correlation. Median (%fT > CT[1 mg/L])/MIC values associated with 1-log reductions were 9.82 and 9.90 for A. baumannii and P. aeruginosa, respectively. Median (%fT > CT[1 mg/L])/MIC associated with stasis was 55.73 for K. pneumoniae. Imipenem/funobactam 500/250 mg q6h 1 h infusion HSR produced >1-log kill against 6/7 A. baumannii, 4/4 P. aeruginosa and stasis against 4/4 K. pneumoniae.CONCLUSIONSImipenem/funobactam showed potent in vivo efficacy against serine carbapenemase-producers. The novel PK/PD index (%fT > CT)/MIC appeared to best describe in vivo activity.

01 Dec 2022·Journal of Global Antimicrobial Resistance

In vitro and in vivo activities of a novel β-lactamase inhibitor combination imipenem/XNW4107 against recent clinical Gram-negative bacilli from China

Article

Author: Xue, Feng ; Zhong, Wei ; Zheng, Bo ; Wang, Qing ; Lv, Yuan ; Yan, Mengyao ; Wu, Yuchuan ; Zhang, Jia ; Chen, Xi ; Li, Yun ; Liu, Xiao

OBJECTIVESXNW4107 is a novel β-lactamase inhibitor that possesses broad activity against serine-β-lactamases. XNW4107 in combination with imipenem exhibited potent in vitro activity against carbapenem-resistant bacteria and particularly against carbapenem-resistant Acinetobacter baumannii. This study aimed to evaluate the in vitro and in vivo antibacterial activities of imipenem/XNW4107.METHODSThe minimum inhibitory concentrations, minimum bactericidal concentrations, time-kill curves, post-antibiotic effects, and spontaneous frequency of resistance were used to investigate the imipenem/XNW4107 in vitro activity. A mouse systemic infection model was used to evaluate the imipenem/XNW4107 in vivo efficacy.RESULTSMIC₉₀ of imipenem/XNW4107 against imipenem-nonsusceptible A. baumannii (n = 106) was 8 mg/L, which was 16-fold lower than the MIC₉₀ of imipenem; the resistance rate decreased from 90% to 20% applying the CLSI imipenem breakpoint. MIC₉₀ of imipenem/XNW4107 against imipenem-resistant Klebsiella pneumoniae (n = 54) was 2 mg/L, which was 128-fold lower than the MIC₉₀ of imipenem; 80% imipenem-nonsusceptible Pseudomonas aeruginosa (n = 101) exhibited MICs of imipenem/XNW4107 from 2 to 8 mg/L, which were 4- to 8-fold lower than the MICs of imipenem. Imipenem/XNW4107 was bactericidal against A. baumannii, K. pneumoniae, and Escherichia coli. The time-kill curves showed that increasing concentrations did not result in progressively increased killing at concentrations >4 × MIC. Imipenem/XNW4107 has a low potential for resistance development in tested strains except for K. pneumoniae. Imipenem/XNW4107 provided good protection against imipenem-resistant A. baumannii and K. pneumoniae in vivo.CONCLUSIONSThe broad-spectrum profile and potent in vitro and in vivo antibacterial activities support imipenem/XNW4107 as a promising investigational candidate.

100 Deals associated with Funobactam

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Gram-Negative Bacterial Infections	Phase 3	US	Evopoint Biosciences Co., Ltd.Startup	06 Oct 2022
Pneumonia, Ventilator-Associated	Phase 3	CN	Evopoint Biosciences Co., Ltd.Startup	14 Sep 2022
Hospital acquired bacterial pneumonia	Phase 3	ES	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
Hospital acquired bacterial pneumonia	Phase 3	FR	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
Hospital acquired bacterial pneumonia	Phase 3	US	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
Hospital acquired bacterial pneumonia	Phase 3	IL	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
VABP	Phase 3	US	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
VABP	Phase 3	ES	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
VABP	Phase 3	FR	Evopoint Biosciences AU Pty Ltd	31 Jul 2022
VABP	Phase 3	IL	Evopoint Biosciences AU Pty Ltd	31 Jul 2022

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