Cefepime-taniborbactam vs Meropenem in Adults With VABP or Ventilated HABP (CERTAIN-2)

A Phase 3 Study to Evaluate Cefepime-taniborbactam Compared to Meropenem in Adults With Ventilator Associated Bacterial Pneumonia (VABP) or Ventilated Hospital Acquired Bacterial Pneumonia (vHABP)

This is a Phase 3, randomized, multicenter, double-blind, non-inferiority study to evaluate the efficacy and safety of cefepime-taniborbactam compared to meropenem in patients ≥ 18 years of age with ventilated HABP or VABP.

Study Overview

• Status: Not yet recruiting
• Conditions: Hospital-acquired Pneumonia; Ventilator-associated Pneumonia
• Intervention / Treatment: Drug: Cefepime-taniborbactam; Drug: Meropenem

• Study Type: Interventional
• Enrollment (Estimated): 316
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Venatorx; Phone Number: 610-644-8935; Email: vnrxclinsci@venatorx.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female, ≥18 years of age.
• The patient or patient's legally authorized/acceptable representative (LAR) has voluntarily signed and dated the IRB/IEC approved ICF
• Meets the clinical diagnosis of ventilated HABP or VABP

• Have at least one of the following clinical criteria:

  1. New onset or worsening of pulmonary symptoms and signs
  2. New onset or worsening of purulent respiratory secretions
  3. Hypoxemia
  4. Need for acute changes in ventilator support

• Have at least one of the following clinical criteria:

  1. Documented fever (defined as body temperature ≥ 38°C [100.4°F]
  2. Hypothermia (defined as body temperature ≤ 35°C [95°F])
  3. White blood cell (WBC) ≥10,000 cells/mm3 or ≤4,500 cells/mm3
  4. >15% immature neutrophils (bands).
• Have new or worsening infiltrate on a pulmonary imaging study that is consistent with bacterial pneumonia within 48 hours prior to randomization.
• Have a lower respiratory tract specimen sent for Gram stain and quantitative culture within 36 hours prior to the first dose of study drug.

Exclusion Criteria:

• Receipt of effective antibacterial treatment for pneumonia for a continuous duration of >24 hours during the previous 72 hours prior to randomization.

• Pneumonia known or suspected to be caused by:

  1. A bacterial pathogen resistant to meropenem, as assessed by susceptibility testing or against which either one or both study drugs lack activity
  2. Viruses, atypical bacteria, or fungi
• Use of non-study systemic gram-negative therapy.
• Confounding respiratory conditions.
• Receiving extracorporeal membrane oxygenation (ECMO).
• Patients with refractory septic shock.
• Active immunosuppression.
• Has a history of serious hypersensitivity (e.g., anaphylaxis), serious allergy, or any serious reaction to cephalosporin, penicillin, carbapenem, or other β-lactam antibiotics.
• Female patients who are pregnant.
• Patients with eGFR <10 mL/min/1.73 m2 or are receiving or starting renal replacement therapy or expected to require renal replacement therapy during the treatment phase of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cefepime-taniborbactam; cefepime-taniborbactam (2g/0.5g) IV every 8 hours.	Drug: Cefepime-taniborbactam; Cefepime-taniborbactam administered 2.5g q8h intravenously (IV) over a 4-hour period for 7 days to 14 days at the investigator's discretion. Dose adjustments for renal function may apply.
Active Comparator: Meropenem; Comparator: meropenem (2g) IV every 8 hours.	Drug: Meropenem; Meropenem will be administered 2g q8h IV over 4 hours for 7 days to 14 days at the investigator's discretion. Dose adjustments for renal function may apply.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACM through Study Day 14	The primary endpoint is ACM, a binary variable, through Study Day 14. The primary endpoint is evaluated in the ITT population and is based on the patient's survival status through Study Day 14.	Evaluated on Day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACM through Study Day 28	ACM through Study Day 28; analyzed in ITT and MITT analysis populations.	Evaluated on Day 29-33
Safety Outcomes	Safety assessments include the incidence of TEAEs and SAEs, and discontinuation of study drug due to TEAEs.	From first dose up to Day 33

Collaborators and Investigators

• Sponsor: Venatorx Pharmaceuticals, Inc.
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Study Director: Carlos Fernando de Oliveira, MD, PhD, MSc, Venatorx Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: December 4, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Actual): December 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: VABP; Bacterial Pneumonia; Hospital Acquired Pneumonia; Ventilated Pneumonia; vHABP
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Cross Infection; Iatrogenic Disease; Healthcare-Associated Pneumonia; Pneumonia; Pneumonia, Bacterial; Pneumonia, Ventilator-Associated; Anti-Infective Agents; Anti-Bacterial Agents; Meropenem; Cefepime
• Other Study ID Numbers: VNRX-5133-301; 2022-502682-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No