RANDOMIZED, ACTIVE-CONTROLLED STUDY TO EVALUATE THE EFFICACY AND SAFETY OF INTRAVENOUS SULBACTAM-ETX2514 IN THE TREATMENT OF PATIENTS WITH INFECTIONS CAUSED BY ACINETOBACTER BAUMANNII-CALCOACETICUS COMPLEX

Not Applicable

Recruiting

• Conditions: -J181 Lobar pneumonia, unspecified-A415 Sepsis due to other Gram-negative organisms; Sepsis due to other Gram-negative organisms; Lobar pneumonia, unspecified; A415; J181

• Registration Number: PER-011-19
• Lead Sponsor: ENTASIS THERAPEUTICS, INC,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-07-18
• Study Completion: 2021-07-07
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 24

Inclusion Criteria

General Inclusion Criteria:
1. A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patient’s legally authorized representative may consent on behalf of the study patient, as permitted by local law and institutional Standard Operating Procedures;
2. Male or female older than 18 years of age;
3. A confirmed diagnosis of a serious infection and the expectation, in the judgment of the Investigator, that the patient’s infection will require treatment with IV antibiotics;
4. A known infection caused by ABC (bacteremia, HABP, VABP, cUTI or AP, or surgical or post-traumatic wound infections) as either a single pathogen or member of a polymicrobial infection based on evidence from culture or, if available, rapid diagnostic test from a sample collected within 72 hours prior to randomization (HABP/VABP patients), AND 1 of the following:
a. Has received no more than 48 hours of effective empiric therapy prior to enrollment;
OR
b. Is clinically failing prior treatment regimens (ie, clinical deterioration or failure to improve after at least 48 hours of antibiotic treatment);
Note: Rapid testing of respiratory specimens utilizing FilmArray 2.0 BPP technology may be used to enable early identification of ABC pneumonia. Patients can be randomized based on the results of the BPP rapid test while awaiting results of cultures from the local laboratory. However, if the respiratory sample does not grow ABC in the local
microbiology laboratory culture, these patients will be withdrawn from the study drug treatment.
5. Expectation, in the judgment of the Investigator, that the patient will survive at least 72 hours with effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study;
6. Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use 2 highly effective methods of contraception (ie, condom, combined oral contraceptive, implant, injectable, indwelling intrauterine device, or a vasectomized partner) from Screening until at least 30 days after administration of the last
dose of study drug; and
7. Male participants must be willing to use condoms during sexual intercourse from Screening until at least 90 days after administration of the last dose of study drug.

Part A-Specific Inclusion Criteria
1. APACHE II score between 10 and 30, inclusive, OR SOFA score more than or equal to 7 at the time of diagnosis of infection. Patients who might be eligible for Part A and are not being treated in an intensive care unit and cannot have an APACHE II or SOFA score performed should have a qSOFA score more than or equal to 2 for enrollment in Part A; and
2. Diagnosed with HABP, VABP, and/or bacteremia according to protocol section 4.1.2

Part B-Specific Inclusion Criteria
1. Has an infection caused by ABC organisms known to be resistant to colistin (defined as MIC more or equal to 4 mg/L by a non-agar based method);
For known colistin-resistant infections, the following must be satisfied:
a. Has a known resistant infection based on evidence from culture and susceptibility testing by a non-agar based method within 72 hours prior to randomization, alone or as a single organism of a polymicrobial infe

Exclusion Criteria

Exclusion criteria
1. Presence of suspected or confirmed deep-seated infection, including lung abscess in patients with pneumonia, that is not planned on being drained within 24 hours after randomization;
2. Evidence of active concurrent community-acquired pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumophila, respiratory syncytial virus, influenza and parainfluenza viruses, Middle East respiratory syndrome coronavirus, etc
3. Presence of suspected or confirmed osteomyelitis, endocarditis, or meningitis, as determined by history and/or physical examination;
4. Irremovable implantable device or line thought to be the potential source of infection;
5. Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) more than 60 mmHg AND having a serum lactate >2 mmol/L (18 mg/dL) despite adequate volume resuscitation;
6. For patients to be enrolled with the primary indication of HABP or VABP, any of the following conditions:
a. Diagnosis of ventilator-associated tracheobronchitis; or
b. Inability to provide proper respiratory specimens for culture. Respiratory samples from expectorated or induced sputum should show <10 squamous epithelial cells and >25 polymorphonuclear neutrophils per 100per field;
7. For patients to be enrolled with the primary indication of cUTI or AP, any of the urologic conditions listed in section 4.2 item 7
8. Moribund patients or patients with evidence of immediately life-threatening disease where, in the opinion of the Investigator, the patient is unlikely to survive more than 72 hours after Day 1;
9. Pregnant or breastfeeding women;
10. APACHE II score >30 at the time of diagnosis of infection
11. Receiving chronic hemodialysis or peritoneal dialysis;
12. Known seizure disorder requiring current treatment with antiseizure medication that, in the opinion of the Investigator, would prohibit the patient from complying with the protocol.
13. Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study;
14. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy;
15. Aspartate aminotransferase (AST) or ALT >3 upper limit of normal (ULN) AND total bilirubin >2 ULN at Screening;
16. Requirement at the time of randomization for any reason, or likely to require during the patient’s participation in the study (from randomization through the LFU Visit), for additional systemic antimicrobial therapy (including Gram negative antibacterial, antiviral, antimycobacterial, or antifungal therapy) other than study drug, with the exception of a single oral dose of any antifungal treatment for vaginal candidiasis
17. Requirement for inhaled antibiotics;
18. Known history of human immunodeficiency virus infection and known recent CD4 count <200/mm3 within the last year or presence of significant immunologic disease or dysfunction
19. Presence of neutropenia (absolute neutrophil count <500/mm3) obtained from a local laboratory at Screening;
20. A QT interval corrected using Fridericia’s formula (QTcF) more than 480 msec
21. History of significant hypersensitivity or allergic reaction to any BL, any contra

Study & Design

• Study Type: Interventional
• Study Design: Not specified