Evaluation of the Efficacy and Safety of Intravenous Imipenem/Cilastatin/XNW4107 in Comparison With Recarbrio in Adults With HABP /VABP (REITAB-2)

February 15, 2023 updated by: Evopoint Biosciences Inc.

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 is 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

450

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • France
      • Argenteuil, France, 95100
        • Not yet recruiting
        • CH Victor Dupouy
        • Contact:
      • Paris, France, 75014
      • Paris, France, 75014
        • Not yet recruiting
        • Groupe Hospitalier Paris Saint-Joseph
        • Contact:
    • Alpes Maritimes
      • Nice, Alpes Maritimes, France, 06200
    • Alsace
      • Strasbourg, Alsace, France, 67000
        • Not yet recruiting
        • Hôpitaux universitaires de Strasbourg
        • Contact:
    • Bas-Rhin
      • Strasbourg, Bas-Rhin, France, 67091
        • Not yet recruiting
        • Nouvel Hopital CIVIL/ Medecine Intensive Reanimation
        • Contact:
    • Gard
      • Nîmes, Gard, France, 30029
    • Grand EST
      • Reims, Grand EST, France, 51100
        • Not yet recruiting
        • Chu Reims- Medical Icu
        • Contact:
    • ILE DE France
      • Suresnes, ILE DE France, France, 92150
        • Not yet recruiting
        • Hopital Foch
        • Contact:
    • Paris
      • Paris 18, Paris, France, 75018
    • Picardie
      • Amiens, Picardie, France, 80054
        • Not yet recruiting
        • intensive Unit Care CHU Amiens Picardie
        • Contact:
  • Israel
      • Hadera, Israel, 38100
        • Not yet recruiting
        • Hillel Yaffe Medical Center
        • Contact:
      • Haifa, Israel, 3339419
        • Not yet recruiting
        • Bnei-Zion Medical Center
        • Contact:
      • Haifa, Israel, 3525408
        • Not yet recruiting
        • Rambam Critical Care division
        • Contact:
      • Tel Aviv, Israel, 64239
        • Not yet recruiting
        • Tel Aviv Medical Center
        • Contact:
    • Center
      • Ramat Gan, Center, Israel, 5262100
        • Not yet recruiting
        • Sheba Medical Center
        • Contact:
    • Central
      • H̱olon, Central, Israel, 58100
        • Not yet recruiting
        • Wolfson medical center
        • Contact:
    • HaMercaz
      • Be'er Ya'aqov, HaMercaz, Israel, 70300
        • Not yet recruiting
        • Shamir Medical Center
        • Contact:
    • Western Galilee
      • Nahariya, Western Galilee, Israel, 2210001
        • Not yet recruiting
        • Galilee Medical Center / Department int med A
        • Contact:
  • Spain
      • Barcelona, Spain, 08041
        • Not yet recruiting
        • Hospital de la Santa Creu i Sant Pau
        • Contact:
      • Barcelona, Spain, 08003
        • Not yet recruiting
        • Hospital del Mar
        • Contact:
      • Barcelona, Spain, 08035
        • Not yet recruiting
        • Hospital Universitari Vall Hebron
        • Contact:
      • Barcelona, Spain, 08036
        • Not yet recruiting
        • Hospital Clinic of Barcelona
        • Contact:
      • Tarragona, Spain, 43007
        • Not yet recruiting
        • Hospital Universitario de Tarragona Joan XXIII
        • Contact:
    • Barcelona
      • Hospitalet de Llobregat, Barcelona, Spain, 08907
  • United States
    • Colorado
      • Denver, Colorado, United States, 80204
        • Not yet recruiting
        • Denver Health and Hospital Authority
        • Contact:
    • Connecticut
      • Hartford, Connecticut, United States, 37920
        • Active, not recruiting
        • Hartford Hospital
    • Florida
      • Miami, Florida, United States, 33136
        • Not yet recruiting
        • Jackson Memorial Hospital (JMH) - Ryder Trauma Center
        • Contact:
      • Tampa, Florida, United States, 33606
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Not yet recruiting
        • University of Maryland Medical Center
        • Contact:
    • Missouri
      • Springfield, Missouri, United States, 65807
    • New York
      • Buffalo, New York, United States, 14215
        • Not yet recruiting
        • VA Medical Center
        • Contact:
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Carolinas Medical Center
        • Contact:
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Recruiting
        • University Hospitals Cleveland Medical Center
        • Contact:
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • Recruiting
        • The University of Tennessee Medical Center
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients willing and able to provide written informed consent or where consent is provided by legally authorized representatives.
  2. Willing and able to comply with all study assessments and adhere to the protocol schedule.
  3. Male or female patients ≥18 years on the day of signing informed consent.
  4. Has HABP or VABP as defined below and requires treatment with IV antibiotic therapy.

  5. All patients must fulfill at least 1 of the following clinical criteria at Screening:

    • New onset or worsening of pulmonary symptoms or signs, such as cough, dyspnea, tachypnea, expectorated sputum production, or requirement for mechanical ventilation
    • Hypoxemia
    • Need for acute changes in the ventilator support system to enhance oxygenation, as determined by worsening oxygenation or needed changes in the amount of positive end-expiratory pressure
    • New onset of or increase in suctioned respiratory secretions, demonstrating evidence of inflammation and absence of contamination.

  6. All patients must have at least 1 of the following symptoms/signs/laboratory abnormalities at screening:

    1. Documented fever
    2. Hypothermia
    3. Leukocytosis with a total peripheral white blood cell (WBC) count ≥10,000 cells/mm³
    4. Leukopenia with total peripheral WBC count <4500 cells/mm³
    5. Greater than 15% immature neutrophils noted on peripheral blood smear.
  7. All patients must have a chest radiograph during Screening or have a previous chest radiograph within 48 hours prior to randomization showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia.
  8. All patients must have a suspected Gram-negative infection involving the lower respiratory tract.
  9. Agree to allow any bacterial isolates obtained from protocol-required specimens related to the current infection to be provided to the Central Microbiology Reference Laboratory for study- related microbiological testing, long-term storage, and other future testing.

Exclusion Criteria:

  1. If a Gram stain from a respiratory sample shows only Gram-positive cocci.
  2. Patients who have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia including COVID-19, or chemical pneumonia.
  3. Patients who have HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction.
  4. Have received effective systemic and inhaled Gram-negative antibacterial drug therapy for the index infection of HABP/VABP for a continuous duration of more than 24 hours during the previous 72 hours prior to randomization.
  5. Has a concurrent condition or infection that, in the investigator's judgment, would preclude evaluation of therapeutic response.
  6. Patients who have central nervous system infection.
  7. Documented presence of immunodeficiency or an immunocompromised condition including hematologic malignancy, bone marrow transplant, known history of human immunodeficiency virus infection with a CD4 count <200/mm³, or requiring frequent or prolonged use of systemic corticosteroids or other immunosuppressive drugs.
  8. Documented or severe hypersensitivity or previous severe adverse drug reaction, especially to any beta-lactam antibiotics, or any of the excipients used in the study drug formulations.
  9. History of a seizure disorder.
  10. Renal function at Screening as estimated glomerular filtrated rate <15 mL/min/1.73㎡, calculated using Modification of Diet in Renal Disease.
  11. Patient is receiving hemodialysis or peritoneal dialysis or micro-dialysis or continuous venovenous hemofiltration or continuous venovenous hemodialysis.

  12. Patient is anticipated to be treated with any of the following medications during the course of study therapy:

    1. Valproic acid or divalproex sodium
    2. Concomitant systemic (IV or oral) Gram-negative antibacterial agents in addition to those designated in the study treatment groups
    3. Concomitant systemic (IV or oral) antifungal or antiviral therapy for the index infection of HABP/VABP.
  13. Life expectancy is <3 days.
  14. Patients in refractory septic shock, defined as persistent hypotension despite adequate fluid resuscitation and vasopressive therapy at the time of randomization.
  15. Patients with 1 or more of the following laboratory abnormalities in baseline specimens: aspartate aminotransferase, alanine aminotransferase >3 × the upper limit of normal (ULN), total bilirubin level >2 × ULN (except for isolated hyperbilirubinemia due to known Gilbert's disease), neutrophils <500 cells/mm³, platelet count <40,000/mm³.
  16. History of active liver disease, cirrhosis.
  17. Patients with an APACHE II score of >30.
  18. Female patients of childbearing potential, who are unable or unwilling to use a highly effective method of birth control during the study and for at least 30 days following the last dose of study medication.
  19. A female who is pregnant or breastfeeding or has a positive pregnancy test at Screening.
  20. Patient is participating in any clinical study of any investigational medication (i.e., non-licensed medication) during the 30 days prior to randomization. COVID-19 vaccines that are given under emergency use authorization are not considered investigational agents.
  21. Any other condition or prior therapy, which, in the opinion of the investigator, would make the patient unsuitable for this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Imipenem/Cilastatin/XNW4107
Imipenem/Cilastatin 500mg/500mg in combination with XNW4107 250mg, Q6h (0.5h Infusion)
Drug: Combination of Imipenem/Cilastatin and XNW4107
Imipenem/Cilastatin 500mg/500mg and XNW4107 250mg for Injection
Active Comparator: Imipenem/Cilastatin/Relebactam
Imipenem/Cilastatin/Relebactam 1.25g Q6h (0.5h Infusion)
Drug: Imipenem/Cilastatin/Relebactam
Imipenem/Cilastatin/Relebactam 1.25 g for Injection
Other Names:
  • Recarbrio

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
all-cause mortality rate
Time Frame: Up to Day 14
The primary endpoint is the Day 14 all-cause mortality rate in the modified-intent-to-treat (MITT) population.
Up to Day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
all-cause mortality rate
Time Frame: Up to Day 28
Day 28 all-cause mortality rate in the MITT population
Up to Day 28
all-cause mortality rate
Time Frame: Up to Day 14 and Up to Day 28
Day 14 and Day 28 all-cause mortality rate in the micro-MITT, extended micro-MITT, Clinically evaluable(CE), Microbiologically evaluable(ME) and Carbapenem-resistant-MITT(CR-MITT) populations
Up to Day 14 and Up to Day 28
clinical success
Time Frame: Day 4; EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]
The proportion of patients with clinical success at Day 4, End of treatment(EOT), Test of cure(TOC) and Late follow-up(LFU) visits in the MITT, micro-MITT , extended micro-MITT, CE, ME, and CR-MITT populations
Day 4; EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]
microbiological success
Time Frame: EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days];
The proportion of patients with microbiological success at EOT and TOC visits in the micro-MITT , extended micro-MITT, and ME populations
EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days];
microbiological success
Time Frame: EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]
The proportion of patients with microbiological success at EOT, TOC and LFU visits in the CR-MITT population
EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]
By-Pathogen microbiological success
Time Frame: EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]
The proportion of patients with by-pathogen microbiological success at EOT, TOC, and LFU visits in the micro-MITT, extended micro-MITT, ME, and CR-MITT population
EOT: from treatment day 7 up to day 15; TOC: Day 21[±2 days]; LFU: Day 28[±3 days]
Adverse events
Time Frame: Up to LFU: Day 28[±3 days]
Incidence of all AEs, including SAEs
Up to LFU: Day 28[±3 days]

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Total number of days in hospital
Time Frame: Up to Day 28
Total number of days in hospital within 28 days after randomization for MITT population
Up to Day 28
Number of days in intensive care unit (ICU)
Time Frame: Up to Day 28
Number of days in intensive care unit (ICU) through 28 days after randomization for MITT population
Up to Day 28
Number of days on a ventilator and ventilator free days
Time Frame: Up to Day 28
Number of days on a ventilator and ventilator free days through 28 days after randomization for the subgroup of VABP patients includingand ventilated-HABP in the MITT population.
Up to Day 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Evopoint Biosciences Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 31, 2022

Primary Completion (Anticipated)

April 1, 2025

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

January 5, 2022

First Submitted That Met QC Criteria

January 10, 2022

First Posted (Actual)

January 24, 2022

Study Record Updates

Last Update Posted (Estimate)

February 16, 2023

Last Update Submitted That Met QC Criteria

February 15, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • XNW4107-302

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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