Safety and Efficacy Study of Cefepime/VNRX-5133 in Patients With Complicated Urinary Tract Infections

Study Overview
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Brief Summary
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This study will assess the safety and efficacy of cefepime/VNRX-5133 compared with meropenem in both eradication of bacteria and in symptomatic response in patients with cUTIs.

Official Title
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A Phase 3, Randomized, Double-blind, Active Controlled Noninferiority Study Evaluating the Efficacy, Safety, and Tolerability of Cefepime/VNRX-5133 in Adults With Complicated Urinary Tract Infections (cUTI), Including Acute Pyelonephritis

Conditions
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Urinary Tract Infections, Acute Pyelonephritis

Intervention / Treatment
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* Drug: Cefepime/VNRX-5133 (taniborbactam)
* Drug: Meropenem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male and female Documented diagnosis of pyuria Documented diagnosis of cUTI or Acute Pyelonephritis (AP) Exclusion Criteria: Receipt of effective antibacterial drug therapy for cUTI for more than 24 hours during the previous 72 hours prior to randomization A urine culture result is resistant to meropenem or a gram negative pathogen is not identified or more than 2 microorganisms are isolated or a confirmed fungal UTI is identified Required use of nonstudy systemic bacterial therapy Suspected or confirmed prostatitis or urinary tract symptoms attributable to sexually transmitted disease Patients with perinephric or renal abscess Patients with renal transplantation or receiving hemodialysis or peritoneal dialysis Abnormal labs

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cefepime/VNRX-5133 (taniborbactam)<br>Cefepime/VNRX-5133 administered q8h intravenously (IV) over a 2-hour period. | Drug: Cefepime/VNRX-5133 (taniborbactam)<br>* Cefepime/VNRX-5133 administered q8h intravenously (IV) over a 2-hour period for 7 days (up to 14 days for patients with bacteremia). Patients will also receive meropenem placebo administered via IV over 30 minutes.<br>|
| Active Comparator: Meropenem<br>Meropenem will be administered q8h IV over 30 minutes. | Drug: Meropenem<br>* Meropenem will be administered q8h IV over 30 minutes for 7 days (up to 14 days for patients with bacteremia). Patients will also receive cefepime/VNRX-5133 placebo administered via IV over a 2-hour period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of microbiological eradication and symptomatic clinical success in the microbiological intent-to-treat (microITT) population at test of cure (TOC) | Microbiologic eradication is defined as demonstration that any gram negative bacterial pathogen found at study entry (≥10^5 CFU/mL) is eradicated to <10^3 CFU/mL. Symptomatic clinical success is defined as symptomatic resolution or return to pre-morbid baseline of all UTI-core symptoms and patient is alive, and patient has not received additional antibacterial therapy for cUTI. | Days 19-23 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Microbiological and symptomatic success at test of cure (TOC) | The proportion of patients with both microbiological success and symptomatic clinical success at TOC in the extended microITT population. | Days 19-23 | 
| Clinical and microbiological success at end of treatment (EOT) and last follow-up (LFU) | The proportion of patients with both microbiological success and symptomatic clinical success at EOT and LFU. | 24 hours after last IV dose, Days 28-35 | 
| Per-patient microbiological success at EOT, TOC and LFU | The proportion of patients with per-patient microbiological success at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 
| Patients with symptomatic clinical success at EOT, TOC and LFU | The proportion of patients with symptomatic clinical success at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 
| Investigator opinion of clinical success at TOC | The proportion of patients with clinical success based on investigator opinion at TOC. | Days 19-23 | 
| Per-pathogen microbiological success at EOT, TOC and LFU | The proportion of patients with per-pathogen microbiological success at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 
| Microbiological and clinical success in cefepime-resistant pathogens at EOT, TOC and LFU | The proportion of patients with both microbiological success and symptomatic clinical success among those with cefepime-resistant pathogens at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 
| Per-patient microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU | The proportion of patients with per-patient microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 
| Per-pathogen microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU | The proportion of patients with per-pathogen microbiological success among those with cefepime-resistant pathogens at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 
| Symptomatic clinical success among those with cefepime-resistant pathogens at EOT, TOC and LFU cefepime-resistant pathogens | The proportion of patients with symptomatic clinical success among those with cefepime-resistant pathogens at EOT, TOC and LFU. | Within 24 hours of last IV dose, Days 19-23, Days 28-35 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bacterial Infections, Cefepime, Meropenem, Complicated Urinary Tract Infections, Anti-Infective Agents, β-Lactamase Inhibitors, VNRX-5133 (taniborbactam)