Health Condition 1: A499- Bacterial infection, unspecified
Conditions
Interventions
Intervention1: ETX2514-Sulbactam: The ETX2514SUL regimen of 1.0 g ETX2514/1.0 g sulbactam should be infused over 3 hours q6h
given for 7 days to 14 days (28 doses to 56 doses), depending on the clinic
Sponsors
Entasis Therapeutics
Eligibility
Inclusion criteria
Inclusion criteria: 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: 1. A signed informed consent form (ICF). If a study patient is unable to provide informed consent due to their medical condition, the patientâ??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 ï?³18 years of age; 3. A confirmed diagnosis of a serious infection and the expectation, in the judgment of the Investigator, that the patientâ??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 (see Section 7.7) 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if the respiratory sample does not grow ABC in the local microbiology laboratory culture, these patients will be withdrawn from the study drug treatment. 5.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 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.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following criteria will be excluded from participation in the study: 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; 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. 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) ï?³60 mmHg AND having a serum lactate >2 mmol/L (18 mg/dL) despite adequate volume resuscitation; Note: Patients who can maintain an MAP ï?³60 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 ï?³60 mmHg are ineligible. If vasopressors are weaned to below these levels, patient enrollment can be reconsidered. 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 25 polymorphonuclear neutrophils per 100ï?´ field; 7. 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; 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; 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 t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary efficacy endpoint for the study is 28-day all-cause mortality in the CRABC m-MITT Population in Part A.Timepoint: 28-day | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Attributable mortality in the CRABC m-MITT Population, if, at the discretion of the Investigator, the death is related to the indication infection (ie, ABC); 2. Clinical cure at TOC in the CRABC m-MITT Population; 3. Clinical cure at TOC in the m-MITT, Clinical Evaluable (CE), Microbiologic Evaluable (ME), and CRABC ME Populations 4.PK exposure of ETX2514 and sulbactam in the PK PopulationTimepoint: 1. 28-day all-cause mortality in the ITT Population Clinical cure at Day 5, Day 7, EOT, and LFU in the m-MITT, CRABC m-MITT, CE, ME, and CRABC ME Populations; 2. Microbiological favorable assessment at Day 5, Day 7, EOT, TOC, and LFU in the m-MITT, CRABC m-MITT, ME, and CRABC ME Populations; 3. 14-day all-cause mortality in the CRABC m-MITT and m-MITT Populations; 4. 28-day all-cause mortality in the m-MITT and CRABC ME Populations; | — |
Countries
Belarus, Brazil, Greece, Hungary, India, Israel, Italy, Lithuania, Mexico, Peru, Russian Federation, Spain, Taiwan, Thailand, Turkey, United States of America
Contacts
Public ContactKirit Sachdev
Medpace Clinical Research India Pvt. Ltd.
Outcome results
None listed