Study to Evaluate the Efficacy and Safety of Intravenous Sulbactam-ETX2514 in the Treatment of Patients With Infections Caused by Acinetobacter Baumannii-calcoaceticus Complex (ATTACK)

August 13, 2021 updated by: Entasis Therapeutics

A 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

This is a 2-part study, with Part A being the randomized, controlled portion of the study in patients with ABC hospital-acquired bacterial pneumonia (HABP), ventilator-associated bacterial pneumonia (VABP), or bacteremia. Part B is the single-group portion of the study and includes ABC infections that are resistant to or have failed colistin or polymyxin B treatment, as detailed in the inclusion criteria.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

207

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belarus
      • Brest, Belarus
        • Entasis Research Site
      • Gomel, Belarus
        • Entasis Research Site
      • Grodno, Belarus
        • Entasis Research Site
      • Minsk, Belarus
        • Entasis Research Site
  • Brazil
      • Belo Horizonte, Brazil
        • Entasis Research Site
      • Campinas, Brazil
        • Entasis Research Site
      • Porto Alegre, Brazil
        • Entasis Research Site
      • Salvador, Brazil
        • Entasis Research Site
      • Sao Jose do Rio Preto, Brazil
        • Entasis Research Site
  • China
      • Beijing, China
        • Entasis Research Site 1
      • Beijing, China
        • Entasis Research Site 2
      • Beijing, China
        • Entasis Research Site 3
      • Changsha, China
        • Entasis Research Site
      • Chongqing, China
        • Entasis Research Site
      • Guangzhou, China
        • Entasis Research Site
      • Hebei, China
        • Entasis Research Site
      • Hefei, China
        • Entasis Research Site 1
      • Hefei, China
        • Entasis Research Site 2
      • Hubei, China
        • Entasis Research Site
      • Nanchang, China
        • Entasis Research Site
      • Nanjing, China
        • Entasis Research Site
      • Nanning, China
        • Entasis Research Site
      • Shanghai, China
        • Entasis Research Site 1
      • Shanghai, China
        • Entasis Research Site 2
      • Shenzhen, China
        • Entasis Research Site
      • Tianjin, China
        • Entasis Research Site
      • Wuhan, China
        • Entasis Research Site
  • Greece
      • Athens, Greece
        • Entasis Research Site 1
      • Athens, Greece
        • Entasis Research Site 3
      • Heraklion, Greece
        • Entasis Research Site
      • Larisa, Greece
        • Entasis Research Site
      • Larissa, Greece
        • Entasis Research Site
      • Thessaloniki, Greece
        • Entasis Research Site
  • Hungary
      • Budapest, Hungary
        • Entasis Research Site 1
      • Budapest, Hungary
        • Entasis Research Site 2
      • Debrecen, Hungary
        • Entasis Research Site
  • India
      • Ahmedabad, India
        • Entasis Research Site
      • Belgaum, India
        • Entasis Research Site
      • Gujrat, India, 382 428
        • Entasis Research Site 2
      • Gujrat, India, 395002
        • Entasis Research Site 1
      • Hyderabad, India
        • Entasis Research Site
      • Kolkata, India
        • Entasis Research Site
      • Pune, India
        • Entasis Research Site
  • Israel
      • Holon, Israel
        • Entasis Research Site
      • Tel Aviv, Israel
        • Entasis Research Site
      • Tel Hashomer, Israel
        • Entasis Research Site
      • Zerifin, Israel
        • Entasis Research Site
  • Korea, Republic of
      • Gyeonggi-do, Korea, Republic of
        • Entasis Research Site
      • Seoul, Korea, Republic of
        • Entasis Research Site 1
      • Seoul, Korea, Republic of
        • Entasis Research Site 2
  • Lithuania
      • Kaunas, Lithuania
        • Entasis Research Site
      • Klaipėda, Lithuania
        • Entasis Research Site
      • Vilnius, Lithuania
        • Entasis Research Site
  • Mexico
      • Guadalajara, Mexico
        • Entasis Research Site 1
      • Guadalajara, Mexico
        • Entasis Research Site 2
      • Mexico DF, Mexico
        • Entasis Research Site
      • Monterrey, Mexico
        • Entasis Research Site
      • San Luis Potosi, Mexico
        • Entasis Research Site
  • Peru
      • Bellavista, Peru
        • Entasis Research Site
      • Cusco, Peru
        • Entasis Research Site
      • Lima, Peru
        • Entasis Research Site
      • San Isidro, Peru
        • Entasis Research Site
      • San Martin de Porres, Peru
        • Entasis Research Site
  • Puerto Rico
      • Ponce, Puerto Rico
        • Entasis Research Site
  • Russian Federation
      • Arkhangelsk, Russian Federation
        • Entasis Research Site
      • Krasnodar, Russian Federation
        • Entasis Research Site
      • Novosibirsk, Russian Federation
        • Entasis Research Site 1
      • Novosibirsk, Russian Federation
        • Entasis Research Site 2
      • Novosibirsk, Russian Federation
        • Entasis Research Site 3
      • Smolensk, Russian Federation
        • Entasis Research Site
      • St Petersburg, Russian Federation, 192242
        • Entasis Research Site 2
      • Tomsk, Russian Federation
        • Entasis Research Site 1
      • Tomsk, Russian Federation
        • Entasis Research Site 2
  • Taiwan
      • Kaohsiung, Taiwan
        • Entasis Research Site
      • Taichung, Taiwan
        • Entasis Research Site
      • Taipei, Taiwan
        • Entasis Research Site
      • Taipei City, Taiwan
        • Entasis Research Site
  • Thailand
      • Chiang Mai, Thailand
        • Entasis Research Site
      • Khon Kaen, Thailand
        • Entasis Research Site
      • Nakhon Ratchasima, Thailand
        • Entasis Research Site
      • Nonthaburi, Thailand
        • Entasis Research Site
  • Turkey
      • Ankara, Turkey
        • Entasis Research Site 1
      • Ankara, Turkey
        • Entasis Research Site 2
      • Eskişehir, Turkey
        • Entasis Research Site
      • Kocaeli, Turkey
        • Entasis Research Site
      • Küçükçekmece, Turkey
        • Entasis Research Site
      • Trabzon, Turkey
        • Entasis Research Site
  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Entasis Research Site
    • Louisiana
      • Shreveport, Louisiana, United States, 71101
        • Entasis Research Site
    • Ohio
      • Cincinnati, Ohio, United States, 45219
        • Entasis Research Site
    • Tennessee
      • Memphis, Tennessee, United States, 38163
        • Entasis Research Site
    • Texas
      • Houston, Texas, United States, 77030
        • Entasis Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

PART A

  1. A confirmed diagnosis of a serious infection that will require treatment with IV antibiotics;

  2. A known infection caused by ABC (bacteremia, HABP, VABP, VP, 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/VP patients), AND 1 of the following:

    1. Has received no more than 48 hrs of potentially effective (ie, Gram negative coverage) antimicrobial therapy prior to the first dose of study drug;
    2. Is clinically failing prior treatment regimens
  3. APACHE II score 10 and 30 inclusive, or SOFA score between 7 and 11 inclusive, at time of diagnosis
  4. Expectation, in the judgment of the Investigator, that the patient will benefit from effective antibiotic therapy and appropriate supportive care for the anticipated duration of the study
  5. Women of childbearing potential (ie, not post-menopausal or surgically sterilized) must have a negative highly sensitive urine or serum pregnancy test before randomization. Participating women of childbearing potential must be willing to consistently use one highly effective method 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.

PART B

1. Has an infection (HABP, VABP, VP, bacteremia, cUTI, AP, or surgical or post-traumatic wound infections) caused by ABC organisms known to be resistant to colistin (defined as MIC ≥4 mg/L by a non-agar based method);

  1. Known to be resistant to colistin or polymyxin B; or
  2. Known intolerance to colistin; or
  3. Has myasthenia gravis or another neuromuscular syndrome(s) that contraindicates colistin and is not ventilated; or
  4. Has acute kidney injury and is receiving renal replacement therapy at study entry.

Exclusion Criteria:

  1. Evidence of active concurrent pneumonia requiring additional antimicrobial treatment
  2. Presence of suspected or confirmed deep seated bacterial infections such as bacterial Gram negative osteomyelitis, endocarditis, or meningitis requiring prolonged therapy, as determined by history and/or physical examination;
  3. Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure (MAP) ≥ 60 mmHg;
  4. Pregnant or breastfeeding women;
  5. Receiving peritoneal dialysis;
  6. Requirement for continuing treatment with probenecid, methotrexate, ganciclovir, valproic acid, or divalproex sodium during the study;
  7. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis, hepatic cirrhosis, hepatic failure, chronic ascites, or hepatic encephalopathy;

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Part A
Drug: ETX2514/Sulbactam + Imipenem/Cilastin
1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h
Other Names:
  • experimental group
Drug: Colistin + Imipenem/Cilastin
2.5 mg/kg colistin IV infused over 30 minutes q12h (after an initial loading dose of colistin 2.5 to 5 mg/kg) plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
Other Names:
  • control group
Drug: ETX2514/Sulbactam + Imipenem/Cilastin
1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
Other Names:
  • experimental group
Experimental: Part B
Drug: ETX2514/Sulbactam + Imipenem/Cilastin
1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h
Other Names:
  • experimental group
Drug: ETX2514/Sulbactam + Imipenem/Cilastin
1.0 g ETX2514/1.0 g sulbactam IV infused over 3 hours q6h plus 1.0 g imipenem/1.0 g cilastatin IV infused over 1 hour q6h.
Other Names:
  • experimental group

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
CRABC m-MITT (Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex Microbiologically Modified Intent-to-Treat Population)
Time Frame: 28 Days
The primary efficacy endpoint for the study is 28-day all-cause mortality in the CRABC m-MITT population in Part A.
28 Days
MITT (Modified Intent To Treat population containing all patients who received any amount of study drug)
Time Frame: 28 days
The primary safety endpoint for the study is the incidence of nephrotoxicity, as measured by the Risk-Injury-Failure-Loss-End-stage renal disease (RIFLE) criteria, in the MITT population in Part A.
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Entasis Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 5, 2019

Primary Completion (Actual)

July 22, 2021

Study Completion (Actual)

July 22, 2021

Study Registration Dates

First Submitted

March 27, 2019

First Submitted That Met QC Criteria

March 27, 2019

First Posted (Actual)

March 28, 2019

Study Record Updates

Last Update Posted (Actual)

August 16, 2021

Last Update Submitted That Met QC Criteria

August 13, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CS2514-2017-0004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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