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

Sponsor
Entasis Therapeutics (Industry)
Overall Status
Completed
CT.gov ID
NCT03894046
Collaborator
(none)
207
Enrollment
92
Locations
2
Arms
22.5
Actual Duration (Months)
2.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: ETX2514/Sulbactam + Imipenem/Cilastin
  • Drug: Colistin + Imipenem/Cilastin
  • Drug: ETX2514/Sulbactam + Imipenem/Cilastin
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
207 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
Study drugs will not be masked due to logistical reasons, every attempt will be made to maintain the blind for patients, all staff at the site, and the Sponsor or its designees, except for the treatment physician and other immediate healthcare providers.
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 5, 2019
Actual Primary Completion Date :
Jul 22, 2021
Actual Study Completion Date :
Jul 22, 2021

Arms and Interventions

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

    		•
    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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. CRABC m-MITT (Carbapenem-resistant Acinetobacter baumannii-calcoaceticus complex Microbiologically Modified Intent-to-Treat Population) [28 Days]

      The primary efficacy endpoint for the study is 28-day all-cause mortality in the CRABC m-MITT population in Part A.

    2. MITT (Modified Intent To Treat population containing all patients who received any amount of study drug) [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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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:

    3. Has received no more than 48 hrs of potentially effective (ie, Gram negative coverage) antimicrobial therapy prior to the first dose of study drug;

    4. Is clinically failing prior treatment regimens

    5. APACHE II score 10 and 30 inclusive, or SOFA score between 7 and 11 inclusive, at time of diagnosis

    6. 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

    7. 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);

    2. Known to be resistant to colistin or polymyxin B; or

    3. Known intolerance to colistin; or

    4. Has myasthenia gravis or another neuromuscular syndrome(s) that contraindicates colistin and is not ventilated; or

    5. 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;

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Entasis Research Site Chicago Illinois United States 60611
    2 Entasis Research Site Shreveport Louisiana United States 71101
    3 Entasis Research Site Cincinnati Ohio United States 45219
    4 Entasis Research Site Memphis Tennessee United States 38163
    5 Entasis Research Site Houston Texas United States 77030
    6 Entasis Research Site Brest Belarus
    7 Entasis Research Site Gomel Belarus
    8 Entasis Research Site Grodno Belarus
    9 Entasis Research Site Minsk Belarus
    10 Entasis Research Site Belo Horizonte Brazil
    11 Entasis Research Site Campinas Brazil
    12 Entasis Research Site Porto Alegre Brazil
    13 Entasis Research Site Salvador Brazil
    14 Entasis Research Site Sao Jose do Rio Preto Brazil
    15 Entasis Research Site 1 Beijing China
    16 Entasis Research Site 2 Beijing China
    17 Entasis Research Site 3 Beijing China
    18 Entasis Research Site Changsha China
    19 Entasis Research Site Chongqing China
    20 Entasis Research Site Guangzhou China
    21 Entasis Research Site Hebei China
    22 Entasis Research Site 1 Hefei China
    23 Entasis Research Site 2 Hefei China
    24 Entasis Research Site Hubei China
    25 Entasis Research Site Nanchang China
    26 Entasis Research Site Nanjing China
    27 Entasis Research Site Nanning China
    28 Entasis Research Site 1 Shanghai China
    29 Entasis Research Site 2 Shanghai China
    30 Entasis Research Site Shenzhen China
    31 Entasis Research Site Tianjin China
    32 Entasis Research Site Wuhan China
    33 Entasis Research Site 1 Athens Greece
    34 Entasis Research Site 3 Athens Greece
    35 Entasis Research Site Heraklion Greece
    36 Entasis Research Site Larisa Greece
    37 Entasis Research Site Larissa Greece
    38 Entasis Research Site Thessaloniki Greece
    39 Entasis Research Site 1 Budapest Hungary
    40 Entasis Research Site 2 Budapest Hungary
    41 Entasis Research Site Debrecen Hungary
    42 Entasis Research Site Ahmedabad India
    43 Entasis Research Site Belgaum India
    44 Entasis Research Site 2 Gujrat India 382 428
    45 Entasis Research Site 1 Gujrat India 395002
    46 Entasis Research Site Hyderabad India
    47 Entasis Research Site Kolkata India
    48 Entasis Research Site Pune India
    49 Entasis Research Site Holon Israel
    50 Entasis Research Site Tel Aviv Israel
    51 Entasis Research Site Tel Hashomer Israel
    52 Entasis Research Site Zerifin Israel
    53 Entasis Research Site Gyeonggi-do Korea, Republic of
    54 Entasis Research Site 1 Seoul Korea, Republic of
    55 Entasis Research Site 2 Seoul Korea, Republic of
    56 Entasis Research Site Kaunas Lithuania
    57 Entasis Research Site Klaipėda Lithuania
    58 Entasis Research Site Vilnius Lithuania
    59 Entasis Research Site 1 Guadalajara Mexico
    60 Entasis Research Site 2 Guadalajara Mexico
    61 Entasis Research Site Mexico DF Mexico
    62 Entasis Research Site Monterrey Mexico
    63 Entasis Research Site San Luis Potosi Mexico
    64 Entasis Research Site Bellavista Peru
    65 Entasis Research Site Cusco Peru
    66 Entasis Research Site Lima Peru
    67 Entasis Research Site San Isidro Peru
    68 Entasis Research Site San Martin de Porres Peru
    69 Entasis Research Site Ponce Puerto Rico
    70 Entasis Research Site Arkhangelsk Russian Federation
    71 Entasis Research Site Krasnodar Russian Federation
    72 Entasis Research Site 1 Novosibirsk Russian Federation
    73 Entasis Research Site 2 Novosibirsk Russian Federation
    74 Entasis Research Site 3 Novosibirsk Russian Federation
    75 Entasis Research Site Smolensk Russian Federation
    76 Entasis Research Site 2 St Petersburg Russian Federation 192242
    77 Entasis Research Site 1 Tomsk Russian Federation
    78 Entasis Research Site 2 Tomsk Russian Federation
    79 Entasis Research Site Kaohsiung Taiwan
    80 Entasis Research Site Taichung Taiwan
    81 Entasis Research Site Taipei City Taiwan
    82 Entasis Research Site Taipei Taiwan
    83 Entasis Research Site Chiang Mai Thailand
    84 Entasis Research Site Khon Kaen Thailand
    85 Entasis Research Site Nakhon Ratchasima Thailand
    86 Entasis Research Site Nonthaburi Thailand
    87 Entasis Research Site 1 Ankara Turkey
    88 Entasis Research Site 2 Ankara Turkey
    89 Entasis Research Site Eskişehir Turkey
    90 Entasis Research Site Kocaeli Turkey
    91 Entasis Research Site Küçükçekmece Turkey
    92 Entasis Research Site Trabzon Turkey

    Sponsors and Collaborators

    • Entasis Therapeutics

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Entasis Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03894046
    Other Study ID Numbers:
    • CS2514-2017-0004
    First Posted:
    Mar 28, 2019
    Last Update Posted:
    Aug 16, 2021
    Last Verified:
    Aug 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Pneumonia
    Bacteremia
    Pneumonia, Bacterial
    Acinetobacter Infections
    Imipenem
    Colistin
    Sulbactam

    Study Results

    No Results Posted as of Aug 16, 2021