A Clinical Trial to Evaluate the Efficacy and Safety of Sulbactam-ETX2514, a New Drug in the Treatment of Patients With ABC Infections Caused by Acinetobacter baumannii-calcoaceticus Complex

Phase 1

• Conditions: Infections Caused by Acinetobacter baumannii-calcoaceticus Complex; MedDRA version: 20.0 Level: LLT Classification code 10003999 Term: Bacteremia System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0 Level: HLT Classification code 10046577 Term: Urinary tract infections System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1 Level: PT Classification code 10037597 Term: Pyelonephritis acute System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0 Level: LLT Classification code 10076918 Term: Hospital acquired pneumonia System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.1 Level: LLT Classification code 10065153 Term: Ventilator associated pneumonia System Organ Class: 10021881 - Infections and infestations; MedDRA version: 20.0 Level: LLT Classification code 10078408 Term: Surgical site infection System Organ Class: 10021881 - Infections and infestations; Therapeutic area: Diseases [C] - Bacterial Infections and Mycoses [C01]

• Registration Number: EUCTR2018-002526-23-GR
• Lead Sponsor: Entasis Therapeutics

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-05-22
• Last Update Posted: 16 December 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 246

Inclusion Criteria

General Inclusion Criteria for Part A and B:
1. 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;
2. Male or female 18 years of age or older;
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 intravenous (IV) antibiotics;
4. 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; 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 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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 248
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

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 e.g. Streptococcus pneumoniae, Haemophilus influenzae, 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) higher or equal to 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 100 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;
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,
15. Aspartate aminotransferase (AST) or alanine aminotransferase (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 Late Fol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified