Efficacy, Safety, Tolerability of Vabomere Compared to Best Available Therapy in Treating Serious Infections in Adults

NCT02168946 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: Rempex 506
• Study Type: interventional
• Target: 77
• Locations: 8 countries
• Sites: 50

Brief Summary

Vabomere™, (meropenem-vaborbactam) is being compared to the Best Available Therapy in the treatment of adults with selected serious infections due to Carbapenem Resistant Enterobacteriaceae

Conditions

Urinary Tract Infection Complicated; Acute Pyelonephritis; Hospital Acquired Bacterial Pneumonia; Ventilator-associated Bacterial Pneumonia; Bacteremia; Abdominal Infection

Outcome Measures

Primary Outcomes (3)

• Proportion of Subjects in the Microbiological Carbapenem-resistant Enterobacteriaceae Modified Intent-to-Treat (mCRE-MITT) Population With a Response of Overall Success [Complicated Urinary Tract Infection (cUTI) or Acute Pyelonephritis (AP) Subjects]

  Overall success is defined as clinical cure \& microbiological eradication. Eradication defined by FDA as the demonstration that the bacterial pathogen(s) found at baseline is reduced to \<10x4 colony forming unit (CFU)/mL urine. Clinical cure defined as complete resolution or significant improvement of the baseline signs \& symptoms, no further antimicrobial warranted.

  at Test of Cure (TOC) visit (Day 12-23)

• All-cause Mortality Rate in the mCRE-MITT Population [Hospital-acquired Bacterial Pneumonia (HABP), Ventilator-associated Bacterial Pneumonia (VABP) and Bacteremia Subjects)

  The All-cause mortality rate at Day 28 in the mCRE-MITT population (HABP/VABP and Bacteremia)

  Day 28

• Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure [Complicated Intra-abdominal Infection (cIAI) Subjects Only]

  Clinical cure defined as complete resolution or significant improvement of the baseline signs and symptoms, no further antimicrobial warranted.

  at TOC visit (Day 12-23)

Secondary Outcomes (13)

• The All-cause Mortality Rate in the mCRE-MITT Population (All Indications)

  at Day 28

• The All-cause Mortality Rate in the m-MITT Population (All Indications)

  at Day 28

• The All-cause Mortality Rate in the mCRE-MITT Population (cUTI/AP)

  at Day 28

• Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure (All Indications)

  at End of Therapy (EOT) visit (7-14 days) and TOC visit (12-23 days)

• Proportion of Subjects in the mCRE-MITT Population With a Clinical Outcome of Cure (cUTI/AP Subjects Only)

  at EOT visit (7-14) and TOC visit (day 12-23)

Study Arms (2)

Vabomere

EXPERIMENTAL

Vabomere (meropenem 2g plus vaborbactam 2g) IV q8h, for up to 14 days

Drug: Vabomere

Best Available Therapy

ACTIVE COMPARATOR

Subjects will receive Best Available Therapy (IV antibiotics)

Drug: Best Available Therapy

Interventions

Vabomere DRUG

Vabomere for IV injection, administered as a 2 g/2 g dose

Also known as: Combination meropenem and vaborbactam, beta-lactamase inhibitor and carbapenem antibiotic

Vabomere

Best Available Therapy DRUG

Antibiotic(s) chosen by Investigator

Also known as: IV Antibiotics

Best Available Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willingness to comply with all study activities and procedures and to provide signed, written informed consent prior to any study procedures. If a subject is unable to provide informed consent due to their medical condition, the subject's legal representative will be provided with study information in order for consent to be obtained.
• Hospitalized male or female, ≥18 years of age.
• Weight ≤185 kg.
• Have a confirmed diagnosis of a serious infection, specifically cUTI or AP, cIAI, HABP, VABP, and/or bacteremia, requiring administration of IV antibacterial therapy.
• Have a known or suspected Carbapenem-Resistant Enterobacteriaceae (CRE) infection.
• Expectation, in the opinion of the Investigator, that the subject's infection will require treatment with IV antibiotics for a minimum of 7 days.
• Expectation that subjects with an estimated creatinine clearance \<10 ml/min (Cockcroft-Gault) will receive hemodialysis at least 2 times per week.
• For cUTI \& AP subjects only: expectation, in the judgment of the Investigator, that any indwelling urinary catheter or instrumentation (including nephrostomy tubes and/or indwelling stents) will be removed or replaced (if removal is not clinically acceptable) before or as soon as possible, but not longer than 12 hours, after randomization.
• For cIAI subjects only: • Expectation, in the judgment of the investigator, that operative drainage/debridement/removal (including open laparotomy, percutaneous drainage, or laparoscopic surgery) of any intra-abdominal collection or other potential source of intra abdominal infection will be performed;
• Expectation that cultures from the aforementioned procedure (including open laparotomy, percutaneous drainage, or laparoscopic surgery) will be sent for microbiological evaluation, including gram stain, culture and susceptibility testing, and Vabomere susceptibility testing.
• Female subjects of childbearing potential, including those who are less than 2 years post menopausal, must agree to, and comply with, using 2 highly effective methods of birth control (i.e., condom plus spermicide, combined oral contraceptive, implant, injectable, indwelling intrauterine device, sexual abstinence, or a vasectomized partner) while participating in this study. In addition, all women of childbearing potential must agree to continue to use 2 forms of birth control throughout the study and for at least 30 days after administration of the last dose of study drug.

You may not qualify if:

• History of any significant hypersensitivity or severe allergic reaction to any beta-lactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams).
• Known or suspected likely infection with New Delhi metallo- (NDM), Verona integron-encoded metallo- (VIM), or IMP-metallo-beta-lactamases or oxacillinase- (OXA)-beta-lactamases (i.e., Class B or Class D beta-lactamases).
• For subjects to be enrolled with the primary indication of cUTI or AP, any of the following urologic conditions:
• Likely to receive ongoing antibacterial drug prophylaxis after treatment of cUTI (e.g., subjects with vesico-ureteral reflux);
• Suspected or confirmed prostatitis;
• Requirement for bladder irrigation with antibiotics or for antibiotics to be administered directly via urinary catheter;
• Previous or planned cystectomy or ileal loop surgery;
• Uncomplicated urinary tract infection (for example, female subjects with urinary frequency, urgency or pain or discomfort without systemic symptoms or signs of infection);
• Complete, permanent obstruction of the urinary tract;
• Suspected or confirmed perinephric or renal corticomedullary abscess;
• Polycystic kidney disease; or
• Any recent history of trauma to the pelvis or urinary tract.
• For subjects to be enrolled with the primary indication of cIAI, any of the following conditions:
• Incomplete drainage of suspected or known intra-abdominal source;
• Likely to receive ongoing antibacterial drug prophylaxis or chronic suppressive therapy after intravenous treatment of cIAI;

Sponsors & Collaborators

• Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.): lead
• Department of Health and Human Services: collaborator

Study Sites (50)

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Hartford, Connecticut, 06102, United States

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Tampa, Florida, 33606, United States

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Augusta, Georgia, 30912, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60612, United States

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Evanston, Illinois, 60201, United States

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Indianapolis, Indiana, 46202, United States

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Detroit, Michigan, 48201, United States

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Royal Oak, Michigan, 48073, United States

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New Brunswick, New Jersey, 08901, United States

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Buffalo, New York, 14215, United States

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Flushing, New York, 11355, United States

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New York, New York, 10032, United States

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The Bronx, New York, 10467, United States

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Charlotte, North Carolina, 28207, United States

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Durham, North Carolina, 27710, United States

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Cleveland, Ohio, 44106, United States

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Philadelphia, Pennsylvania, 19104, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Charlottesville, Virginia, 22908, United States

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Buenos Aires, C1405CNF, Argentina

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Córdoba, 5016, Argentina

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La Plata, B1900AXI, Argentina

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Mendoza, 5500, Argentina

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São José do Rio Preto, São Paulo, 05652-900, Brazil

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Belo Horizonte, 30150-221, Brazil

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Curitiba, 81050-000, Brazil

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Porto Alegre, 90035-903, Brazil

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São Paulo, 05652-900, Brazil

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São Paulo, 14048-900, Brazil

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São Paulo, SP, Brazil

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Barranquilla, Colombia

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Bogotá, 0, Colombia

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Medellín, 4, Colombia

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Athens, 106 76, Greece

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Athens, 11527, Greece

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Athens, 12462, Greece

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Thessaloniki, 54636, Greece

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Haifa, 31096, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 52621, Israel

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Tel Aviv, 64239, Israel

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Bologna, 40138, Italy

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Florence, 50134, Italy

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Genova, 16132, Italy

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Pisa, 56124, Italy

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Rome, 00161, Italy

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Udine, 33100, Italy

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Manchester, M23 9LT, United Kingdom

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Manchester, MI39WL, United Kingdom

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Related Publications (2)

• Bhowmick T. Clinical Outcomes of Patient Subgroups in the TANGO II Study. Infect Dis Ther. 2021 Mar;10(1):35-46. doi: 10.1007/s40121-021-00405-x. Epub 2021 Feb 9.

  PMID: 33565042 DERIVED

• Wunderink RG, Giamarellos-Bourboulis EJ, Rahav G, Mathers AJ, Bassetti M, Vazquez J, Cornely OA, Solomkin J, Bhowmick T, Bishara J, Daikos GL, Felton T, Furst MJL, Kwak EJ, Menichetti F, Oren I, Alexander EL, Griffith D, Lomovskaya O, Loutit J, Zhang S, Dudley MN, Kaye KS. Effect and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections: The TANGO II Randomized Clinical Trial. Infect Dis Ther. 2018 Dec;7(4):439-455. doi: 10.1007/s40121-018-0214-1. Epub 2018 Oct 1.

  PMID: 30270406 DERIVED

MeSH Terms

Conditions

Bacteremia; Intraabdominal Infections

Interventions

meropenem and vaborbactam; vaborbactam; beta-Lactamase Inhibitors; Anti-Bacterial Agents

Condition Hierarchy (Ancestors)

Bacterial Infections; Bacterial Infections and Mycoses; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Anti-Infective Agents; Therapeutic Uses

Limitations and Caveats

Enrollment Challenges required the Sponsor to terminate the study early which led to a smaller number of patients being enrolled.

Results Point of Contact

• Title: Global Health Science Center
• Organization: Rempex Pharmaceuticals, A Wholly Owned Subsidiary of Melinta Therapeutics, Inc.

medinfo@melinta.com

1-844-633-6568

Study Officials

• Karen Fusaro

  Sponsor GmbH

  STUDY DIRECTOR

• Keith Kaye

  Wayne State University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Blinded adjudication committee
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2014
• First Posted: June 20, 2014
• Study Start: July 1, 2014
• Primary Completion: July 21, 2017
• Study Completion: July 21, 2017
• Last Updated: March 4, 2019
• Results First Posted: December 11, 2018

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (2); BR (7); US (20); IL (4); IT (6); AR (4); GR (4); CO (3)