Clinical trial NCT05204563: Imipenem/Cilastatin-XNW4107 Versus Imipenem/Cilastatin/Relebactam for Treatment of Participants With Bacterial Pneumonia (XNW4107-302, REITAB-2)
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hospital Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia
Lead sponsor: Evopoint Biosciences Inc.
Sponsor class: INDUSTRY
First posted: 2022-01-24
Enrollment: 450
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Has HABP or VABP as defined below and requires treatment with IV antibiotic therapy. Fulfills clinical criteria, with onset of criteria occurring after more than 48 hours of hospitalization or within 7 days after discharge from a hospital (for HABP); or at least 48 hours after mechanical ventilation (for VABP)
2. Fulfills clinical criteria with symptoms or signs of cough, expectorated sputum production, dyspnea, worsening oxygenation, increase in respiratory secretions, fever/ hypothermia..
3. Fulfills laboratory test criteria with Leukocytosis/ Leukocytosis/ increase in immature neutrophils
4. Fulfill radiograph criteria with presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia in X-ray/ Chest CT.
5. Female subjects of childbearing potential, who are willing to birth control during the study and for at least 30 days following the last dose of study medication. Male subjects with female sexual partners of childbearing potential are eligible for inclusion if they agree to use birth control for 90 days following the last dose of study medication. Male subjects must agree not to donate sperm

Exclusion Criteria:

1. Gram stain from a respiratory sample shows only Gram-positive cocci.
2. Have known or suspected community-acquired bacterial pneumonia, atypical pneumonia, viral pneumonia including Coronavirus disease, or chemical pneumonia.
3. Have HABP/VABP caused by an obstructive process, including lung cancer or other known obstruction.
4. Have received effective antibacterial drug therapy for the index infection of HABP/VABP for more than 24 hours during the previous 72 hours .
5. Have central nervous system infection.
6. Documented presence of immunodeficiency or an immunocompromised condition
7. 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.
8. History of a seizure disorder requiring ongoing treatment with anti-convulsive therapy or prior treatment with anti-convulsive therapy within the last 3 years.
9. eGFR \<15 mL/min/1.73㎡.
10. Patient is receiving hemodialysis or peritoneal dialysis.
11. Anticipated to be treated with any of Valproic acid or divalproex sodium, concomitant systemic Gram-negative antibacterial agents, or concomitant systemic antifungal or antiviral therapy for the index infection of HABP/VABP.
12. Life expectancy is \<3 days.
13. Patients in refractory septic shock
14. Patients with 1 or more of laboratory abnormalities in baseline specimens.
15. History of active liver disease or cirrhosis.
16. APACHE II score of \>30.
17. A female who is pregnant or breastfeeding or has a positive pregnancy test at Screening.

Primary outcomes:
measure: Day 14 all-cause mortality rate
timeFrame: Up to Day 14
Secondary outcomes:
measure: Day 28 all-cause mortality rate
timeFrame: Up to Day 28
measure: The proportion of subjects with clinical success at Day 4
timeFrame: Day 4
measure: The proportion of subjects with clinical success at EOT
timeFrame: at end of treatment (EOT) of each patient, up to 14 days
measure: The proportion of subjects with clinical success at TOC
timeFrame: at test-of-cure (TOC), up to 14 days
measure: The proportion of subjects with clinical success at LFU
timeFrame: at Late Follow-up (LFU), up to 31 days
measure: The proportion of subjects with overall success at EOT
timeFrame: at end of treatment (EOT), up to 14 days
measure: The proportion of subjects with overall success at TOC
timeFrame: at test of cure (TOC), up to 14 days
measure: The proportion of subjects with overall success at LFU
timeFrame: at Late Follow-up (LFU), up to 31 days
Other outcomes:
Locations:
city: Denver
country: United States
facility: Denver Health and Hospital Authority
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Miami
country: United States
facility: Jackson Memorial Hospital (JMH) - Ryder Trauma Center
state: Florida
city: Tampa
country: United States
facility: USF-TGH
state: Florida
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Springfield
country: United States
facility: Cox Health
state: Missouri
city: Buffalo
country: United States
facility: VA medical center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Knoxville
country: United States
facility: The University of Tennessee Medical Center
state: Tennessee
city: Nice
country: France
facility: CHU de Nice
state: Alpes Maritimes
city: Strasbourg
country: France
facility: Hôpitaux Universitaires de Strasbourg
state: Alsace
city: Strasbourg
country: France
facility: Nouvel Hopital CIVIL/ Medecine Intensive Reanimation
state: Bas-Rhin
city: Nîmes
country: France
facility: Chu Nimes
state: Gard
city: Reims
country: France
facility: Chu Reims- Medical Icu
state: Grand Est
city: Suresnes
country: France
facility: Hôpital Foch
state: Ile de France
city: Paris 18
country: France
facility: APHP
state: Paris
city: Amiens
country: France
facility: intensive Unit Care CHU Amiens Picardie
state: Picardie
city: Argenteuil
country: France
facility: CH victor dupouy
city: Paris
country: France
facility: Cochin
city: Paris
country: France
facility: Groupe Hospitalier Paris Saint-Joseph
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
state: Center
city: H̱olon
country: Israel
facility: Wolfson Medical Center
state: Central
city: Be'er Ya'aqov
country: Israel
facility: Shamir Medical Center
state: HaMercaz
city: Nahariya
country: Israel
facility: Galilee Medical Center / Department int med A
state: Western Galilee
city: Hadera
country: Israel
facility: Hillel Yaffe Medical Center
city: Haifa
country: Israel
facility: Bnei-Zion Medical Center
city: Haifa
country: Israel
facility: Rambam Critical Care division
city: Tel Aviv
country: Israel
facility: Tel Aviv Medical Center
city: Hospitalet de Llobregat
country: Spain
facility: Bellvitge University Hospital
state: Barcelona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall Hebron
city: Barcelona
country: Spain
facility: Hospital Clínic of Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Tarragona
country: Spain
facility: Hospital Universitario de Tarragona Joan XXIII
Study officials:
affiliation: Evopoint Biosciences USA, Inc.)
name: Jason Le
role: STUDY_CHAIR
References: