Imipenem/Cilastatin-XNW4107 Versus Imipenem/Cilastatin/Relebactam for Treatment of Participants With Bacterial Pneumonia (XNW4107-302, REITAB-2)

Phase 3

Recruiting

• Conditions: Hospital Acquired Bacterial Pneumonia or Ventilator-Associated Bacterial Pneumonia
• Interventions: Drug: Imipenem/Cilastatin/Relebactam; Drug: Combination of Imipenem/Cilastatin and XNW4107

• Registration Number: NCT05204563
• Lead Sponsor: Evopoint Biosciences Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-05
• Study First Submitted QC: 2022-01-10
• Study First Posted: 2022-01-24
• Study Start: 2022-07-31
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-06
• Last Update Posted: 2023-03-08
• Primary Completion: 2025-04
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 450

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imipenem/Cilastatin/Relebactam	Imipenem/Cilastatin/Relebactam	Imipenem/Cilastatin/Relebactam 1.25g Q6h (0.5h Infusion)
Imipenem/Cilastatin/XNW4107	Combination of Imipenem/Cilastatin and XNW4107	Imipenem/Cilastatin 500mg/500mg in combination with XNW4107 250mg, Q6h (0.5h Infusion)

Primary Outcome Measures

Name	Time	Method
Day 14 all-cause mortality rate	Up to Day 14	all-cause mortality rate at day 14

Secondary Outcome Measures

Name	Time	Method
The proportion of subjects with clinical success at LFU	at Late Follow-up (LFU), up to 31 days	The proportion of subjects with clinical success at LFU
Day 28 all-cause mortality rate	Up to Day 28	all-cause mortality rate at day 28
The proportion of subjects with clinical success at Day 4	Day 4	The proportion of subjects with clinical success at Day 4
The proportion of subjects with clinical success at EOT	at end of treatment (EOT) of each patient, up to 14 days	The proportion of subjects with clinical success at EOT
The proportion of subjects with clinical success at TOC	at test-of-cure (TOC), up to 14 days	The proportion of subjects with clinical success at TOC
The proportion of subjects with overall success at EOT	at end of treatment (EOT), up to 14 days	The proportion of subjects with overall success at EOT
The proportion of subjects with overall success at TOC	at test of cure (TOC), up to 14 days	The proportion of subjects with overall success at TOC
The proportion of subjects with overall success at LFU	at Late Follow-up (LFU), up to 31 days	The proportion of subjects with overall success at LFU

Trial Locations

Locations (35)

Jackson Memorial Hospital (JMH) - Ryder Trauma Center; 🇺🇸 Miami, Florida, United States

Groupe Hospitalier Paris Saint-Joseph; 🇫🇷 Paris, France

Hôpital Foch; 🇫🇷 Suresnes, ILE DE France, France

CHU de Nice; 🇫🇷 Nice, Alpes Maritimes, France

Chu Reims- Medical Icu; 🇫🇷 Reims, Grand EST, France

Carolinas Medical Center; 🇺🇸 Charlotte, North Carolina, United States

Hospital Universitario de Tarragona Joan XXIII; 🇪🇸 Tarragona, Spain

Denver Health and Hospital Authority; 🇺🇸 Denver, Colorado, United States

Cochin; 🇫🇷 Paris, France

Hospital Clínic of Barcelona; 🇪🇸 Barcelona, Spain

intensive Unit Care CHU Amiens Picardie; 🇫🇷 Amiens, Picardie, France

Bellvitge University Hospital; 🇪🇸 Hospitalet de Llobregat, Barcelona, Spain

Shamir Medical Center; 🇮🇱 Be'er Ya'aqov, HaMercaz, Israel

Hospital del Mar; 🇪🇸 Barcelona, Spain

Hospital Universitari Vall Hebron; 🇪🇸 Barcelona, Spain

University of Maryland Medical Center; 🇺🇸 Baltimore, Maryland, United States

Cox Health; 🇺🇸 Springfield, Missouri, United States

USF-TGH; 🇺🇸 Tampa, Florida, United States

CH victor dupouy; 🇫🇷 Argenteuil, France

Wolfson Medical Center; 🇮🇱 H̱olon, Central, Israel

Hospital de la Santa Creu i Sant Pau; 🇪🇸 Barcelona, Spain

Chu Nimes; 🇫🇷 Nîmes, Gard, France

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

The University of Tennessee Medical Center; 🇺🇸 Knoxville, Tennessee, United States

VA medical center; 🇺🇸 Buffalo, New York, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Hôpitaux Universitaires de Strasbourg; 🇫🇷 Strasbourg, Alsace, France

Nouvel Hopital CIVIL/ Medecine Intensive Reanimation; 🇫🇷 Strasbourg, Bas-Rhin, France

Galilee Medical Center / Department int med A; 🇮🇱 Nahariya, Western Galilee, Israel

Hillel Yaffe Medical Center; 🇮🇱 Hadera, Israel

APHP; 🇫🇷 Paris 18, Paris, France

Sheba Medical Center; 🇮🇱 Ramat Gan, Center, Israel

Tel Aviv Medical Center; 🇮🇱 Tel Aviv, Israel

Bnei-Zion Medical Center; 🇮🇱 Haifa, Israel

Rambam Critical Care division; 🇮🇱 Haifa, Israel