|Age:||18 years or older|
|Keywords:||Acinetobacter baumannii-calcoaceticus Complex, infection|
|Type:||Drug study, Phase 3|
The study team will make sure you qualify to take part in the study. Qualified participants will receive detailed information about the study. This may include a list of study-related tests and procedures.
Patients who meet all of the following general inclusion criteria, in addition to the specific inclusion criteria listed below for Parts A and B, will be eligible to participate in the study:
A signed informed consent form. 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;
Male or female 18 years of age;
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 intravenous (IV) antibiotics;
A known infection caused by ABC (bacteremia, HABP, VABP, complicated urinary tract infection [cUTI] or acute pyelonephritis [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 (ie, prior to first dose of study drug); 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 Biofire® FilmArray® 2.0 Pneumonia Panel (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
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;
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
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.
Patients who meet any of the following criteria will be excluded from participation in the study:
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; Note: Patients with an empyema who will have drainage within 24 hours of Screening and who are expected to be able to be treated with 14 or fewer days of antibiotics are allowed.
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;
Presence of suspected or confirmed osteomyelitis, endocarditis, or meningitis, as determined by history and/or physical examination;
Irremovable implantable device or line thought to be the potential source of infection;
Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) 60 mmHg; Note: Patients who can maintain an MAP 60 mmHg on a reasonable dose of pressors or are weaning off of pressors may be considered. Patients who require more than the maximal dose of 2 vasopressors to maintain an MAP 60 mmHg are ineligible. If vasopressors are weaned to below these levels, patient enrollment can be reconsidered.
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 100 field;
For patients to be enrolled with the primary indication of cUTI or AP, any of the following urologic conditions: a. Likely to receive ongoing antibacterial drug prophylaxis after treatment of cUTI (eg, patients with vesico-uretal reflux); b. Suspected or confirmed prostatitis; c. Requirement for bladder irrigation with antibiotics or for antibiotics to be administered directly via urinary catheter; d. Previous or planned cystectomy or ileal loop surgery; e. Uncomplicated urinary tract infection (eg, female patients with urinary frequency, urgency, or pain or discomfort without systemic symptoms or signs of infection); f. Complete, permanent obstruction of the urinary tract; g. Suspected or confirmed perinephric or renal corticomedullary abscess; h. Polycystic kidney disease; or i. Any recent history of trauma to the pelvis or urinary tract;
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;
Pregnant or breastfeeding women;
APACHE II score >30 at the time of diagnosis of infection; Note: For Part B, an APACHE II or SOFA score is only required if able to be calculated. A qSOFA score must be calculated for all patients without an APACHE II score. Glasgow coma score for APACHE II calculation should be the best response prior to initiation of sedation/neuromuscular blockade, even if sedation has been in use for >24 hours.
Receiving chronic hemodialysis or peritoneal dialysis; Note: Short-term renal replacement therapy and acute intermittent hemodialysis are permitted, and these patients will be enrolled in Part B.
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. Patients with a history of epilepsy or who are on stable treatment (ie, no recurrent episodes in the past 30 days and no history of imipenem-associated seizures) may be considered for enrollment in the study;
Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study;
Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy;
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 upper limit of normal (ULN) AND total bilirubin >2 ULN at Screening; Note: Patients with AST or ALT up to 5 ULN are eligible if these elevations are acute and are documented as being directly related to the infectious process being treated.
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 Late Follow-up [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;
Requirement for inhaled antibiotics;
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, as determined by a current diagnosis of an Acquired Immune Deficiency Syndrome-defining illness;
Presence of neutropenia (absolute neutrophil count <500/mm3 ) obtained from a local laboratory at Screening;
A QT interval corrected using Fridericia’s formula 480 msec;
History of significant hypersensitivity or allergic reaction to any β-lactam (BL), any contraindication to the use of cilastatin based on local approved prescribing information (eg, Summary of Medicinal Product Characteristics), any contraindication to the excipients used in the respective formulations, or any contraindication to the use of BL antibiotics;
Participation in a clinical study involving investigational medication or an investigational device within the last 30 days or 5 half-lives, whichever is longer, prior to Day 1;
Any condition that, in the opinion of the Investigator, would compromise the safety of the patient or the quality of the data or require greater than 14 days of treatment with antibiotics;
Unable or unwilling, in the opinion of the Investigator, to comply with the protocol;
Has previously received ETX2514 in this study; or
For Part A only, patients with an infection known to be resistant to colistin (defined as MIC 4 mg/L by a non-agar based method), with a known intolerance to colistin, or taking any drug that prevents them from receiving colistin.
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