P3 Study to Assess Efficacy and Safety of Cefepime/Nacubactam and Aztreonam/Nacubactam Versus Best Available Therapy for Adults With Infection Due to Carbapenem Resistant Enterobacterales

NCT05905055 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: OP0595-6
• Study Type: interventional
• Target: 126
• Locations: 14 countries
• Sites: 54

Brief Summary

This study is a multi-center, randomized, single-blind, parallel-group study to assess the efficacy and safety, when nacubactam is coadministered with cefepime or aztreonam, compared with best available therapy (BAT), in the treatment of patients with cUTI, AP, HABP, VABP, and cIAI, due to Carbapenem Resistant Enterobacterales.

Conditions

Complicated Intra-abdominal Infection; Complicated Urinary Tract Infection; Acute Pyelonephritis; Hospital-acquired Bacterial Pneumonia; Ventilator-associated Bacterial Pneumonia

Keywords

nacubactam; OP0595; Integral-2

Outcome Measures

Primary Outcomes (1)

• The primary efficacy endpoint is the proportion of patients with overall treatment success at TOC across all infection types (ie, cUTI, AP, HABP, VABP, and cIAI), which is a composite endpoint derived from the efficacy outcomes of each infection type.

  For cUTI and AP, the composite clinical outcome of cure and the microbiological outcome of eradication are defined as the outcome of cure. For HABP and VABP, the clinical success is defined as the outcome of cure. For cIAI, the clincal success is defined as the outcome of cure.

  TOC (Test of Cure visit): 7 [±2] days after EOT (end of treatment) [Day 10 to 23 after the start of treatment]

Secondary Outcomes (21)

• The proportion of patients with overall treatment outcome of success across all infection types

  Outcome measurements were assessed at various visits: EA (Early Assessment): Day 3 to 5 days, EOT: (End of Treatment): Day 5 to Day 14, FUP (Follow-Up visit): Day 17 to Day 30

• The proportion of patients with a clinical outcome of cure per type of resistance

  TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]

• The proportion of patients with a microbiological outcome of eradication per type of pathogen and per type of resistance

  TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]

• The all-cause mortality rate at Day 28 by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types

  Day 28 (+ 2days)

• The proportion of patients with a clinical outcome of cure by each infection type (ie, cUTI/AP, HABP/VABP, or cIAI) and across all infection types

  TOC (Test of Cure visit):7 [±2] days after EOT [Day 10 to 23]

Study Arms (3)

co-administration of cefepime and nacubactam

EXPERIMENTAL

co-administration of 2 g cefepime and 1 g nacubactam q8h (60 min. infusion)

Drug: co-administration of cefepime and nacubactam

co-administration of aztreonam and nacubactam

EXPERIMENTAL

co-administration of 2 g aztreonam and 1g nacubactam q8h (60 min. infusion)

Drug: co-administration of aztreonam and nacubactam

BAT

ACTIVE COMPARATOR

Best Available Therapy

Drug: BAT

Interventions

BAT DRUG

Dosage of BAT will be based per site's standard of care

BAT

co-administration of cefepime and nacubactam DRUG

2 g cefepime and 1 g nacubactam every 8 hours for at least 5 days and up to 14 days via IV infusion over a period of 60 minutes

co-administration of cefepime and nacubactam

co-administration of aztreonam and nacubactam DRUG

2 g aztreonam and 1 g nacubactam every 8 hours for at least 5 days and up to 14 days via IV infusion over a period of 60 minutes

co-administration of aztreonam and nacubactam

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients at least 18 years of age (or age of legal consent, whichever is older) at the time of obtaining informed consent and who can be hospitalized throughout the Treatment Period;
• Weight at most 140 kg;
• The following criteria must be satisfied:
• a. For known CRE infection, meets either of the following (i or ii): i. Has a known CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence from CRE culture, susceptibility testing, and possible carbapenemase phenotypic testing (or possible molecular testing) within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; AND Has received no more than 24 hours of an antimicrobial agent to which the known CRE is known to be susceptible within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; OR ii. Has a known CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence from CRE culture, susceptibility testing, and possible carbapenemase phenotypic testing (or possible molecular testing) within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; AND Has documented clinical evidence of failure (ie, clinical deterioration or failure to improve) after at least 48 hours of treatment with an antimicrobial agent to which the known CRE is known to be susceptible within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; b. For suspected CRE infection, meets the following (i or ii): i. Has a suspected CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence which may be determined within 90 days prior to the first dose of study drug through rapid diagnostic tests, active surveillance cultures, other documentation of CRE colonization, or prior infection due to a CRE pathogen; AND Has received no more than 24 hours of empiric antimicrobial therapy for Gram negative organisms within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug； ii. Has a suspected CRE infection, alone or as a single isolate of a polymicrobial infection, based on evidence which may be determined within 90 days prior to the first dose of study drug through rapid diagnostic tests, active surveillance cultures, other documentation of CRE colonization, or prior infection due to a CRE pathogen; AND Has documented clinical evidence of failure (ie, clinical deterioration or failure to improve) after at least 48 hours of treatment with empiric antimicrobial therapy for Gram-negative organisms within 72 hours (or 96 hours for cIAI) prior to the first dose of study drug; Note: CRE is defined as Enterobacterales by susceptibility data of MIC at least 2 microg/mL to imipenem or meropenem OR imipenem or meropenem disk diffusion (zone diameter \< 22 mm). If MIC or disk diffusion data are not available in the local laboratory or before the availability of MIC or disk diffusion results, each site can use other methods and criteria in the institution (eg, phenotypic or molecular testing) as the initial evidence of CRE for enrollment. In any case, pathogen identification and susceptibility testing performed at the central laboratory will be used to determine CRE in the final study analysis.

You may not qualify if:

• Has a history of serious allergy, hypersensitivity (eg, anaphylaxis), or any serious allergic reaction to carbapenems, cephems, penicillins, other beta-lactam antibiotics, or any BLIs (eg, tazobactam, sulbactam, or clavulanic acid)
• Has known or suspected single or concurrent infection with Acinetobacter spp., metallo-β-lactamase (MBL) producing Pseudomonas aeruginosa, or other organisms that are not adequately covered by the study drug (eg, concurrent viral, mycobacterial, or fungal infection) and need to be managed with other anti-infectives; Note: Patients with qualifying Gram-negative pathogen co-infected with a Gram-positive pathogen may be administered narrow spectrum, open-label glycopeptide (eg, vancomycin), oxazolidinone (eg, linezolid), or daptomycin concomitantly with the study drug at the discretion of the Investigator. Patients with cIAI may receive metronidazole in addition to cefepime/nacubactam, aztreonam/nacubactam, or as part of BAT if anaerobic coverage is deemed necessary
• Has only a Gram-positive organism pathogen isolated from study-qualifying culture;

Sponsors & Collaborators

• Meiji Seika Pharma Co., Ltd.: lead

Study Sites (54)

Meiji Research Site

Changsha, China

Location

Meiji Research Site

Chongqing, China

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Meiji Research Site

Fuyang, China

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Meiji Research Site

Guangzhou, China

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Meiji Research Site

Hangzhou, China

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Meiji Research Site

Hefei, China

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Meiji Research Site

Nanjing, China

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Meiji Research Site

Nanning, China

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Meiji Research Site

Quanzhou, China

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Meiji Research Site

Shanghai, China

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Meiji Research Site

Shenzhen, China

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Meiji Research Site

Shijiazhuang, China

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Meiji Research Site

Wuxi, China

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Meiji Research Site

Xuzhou, China

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Meiji Research Site

Zagreb, Croatia

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Meiji Research Site

Kyjov, Czechia

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Meiji Research Site

Limoges, France

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Meiji Research Site

Nîmes, France

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Meiji Research Site

Paris, France

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Meiji Research Site

Strasbourg, France

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Meiji Research Site

Kutaisi, Georgia

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Meiji Research Site

Tbilisi, Georgia

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Meiji Research Site

Zestaponi, Georgia

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Meiji Research Site

Athens, Greece

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Meiji Research Site

Be’er Ya‘aqov, Israel

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Meiji Research Site

Ramat Gan, Israel

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Meiji Research Site

Tel Aviv, Israel

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Meiji Research Site

Nankoku, Kochi, Japan

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Meiji Research Site

Hiroshima, Japan

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Meiji Research Site

Kanazawa, Japan

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Meiji Research Site

Nagasaki, Japan

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Meiji Research Site

Nankoku, Japan

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Meiji Research Site

Ōta-ku, Japan

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Meiji Research Site

Shinjuku-ku, Japan

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Meiji Research Site

Toyoake, Japan

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Meiji Research Site

Daugavpils, Latvia

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Meiji Research Site

Liepāja, Latvia

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Meiji Research Site

Riga, Latvia

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Meiji Research Site

Valmiera, Latvia

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Meiji Research Site

Nitra, Slovakia

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Meiji Research Site

Svidník, Slovakia

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Meiji Research Site

Córdoba, Spain

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Meiji Research Site

Madrid, Spain

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Meiji Research Site

Kaohsiung City, Taiwan

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Meiji Research Site

Taichung, Taiwan

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Meiji Research Site

Taipei, Taiwan

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Meiji Research Site

Bangkok, Thailand

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Meiji Research Site

Chiang Mai, Thailand

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Meiji Research Site

Khon Kaen, Thailand

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Meiji Research Site

Ankara, Turkey (Türkiye)

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Meiji Research Site

Eskişehir, Turkey (Türkiye)

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Meiji Research Site

Istanbul, Turkey (Türkiye)

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Meiji Research Site

İzmit, Turkey (Türkiye)

Location

Meiji Research Site

Trabzon, Turkey (Türkiye)

Location

MeSH Terms

Interventions

nacubactam

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2023
• First Posted: June 15, 2023
• Study Start: September 22, 2023
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

CN (14); LA (4); SL (2); TU (5); GR (1); IL (3); CR (1); CZ (1); FR (4); ES (2); TW (3); TH (3); GE (3); JP (8)