Testing Vabomere for serious bacterial infections in children

An Open Label, Dose-finding, Pharmacokinetics, Safety, and Tolerability Study of a Single Dose Infusion of VABOMERE (Meropenem-Vaborbactam) in Pediatric Subjects From Birth to Less Than 18 Years of Age With Serious Bacterial Infections

This study is testing a new antibiotic called Vabomere to see if it can safely help children in the hospital who have serious bacterial infections.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 67 (estimated)
• Ages: N/A to 17 Years
• Sex: All
• Sponsor: Melinta Therapeutics, Inc. (Industry-sponsored)
• Locations: 10 sites (Little Rock, Arkansas and 9 other locations)
• Trial ID: NCT02687906 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety, pharmacokinetics, and optimal dosing of Vabomere (meropenem-vaborbactam) in pediatric patients aged from birth to under 18 years who are hospitalized with serious bacterial infections. The trial focuses on children receiving systemic antibiotics or those needing prophylactic antibiotic treatment during surgery. It aims to address the growing issue of antibiotic resistance, particularly against carbapenem-resistant bacteria, by assessing a new combination therapy. Participants will be monitored in a hospital setting for at least six hours after receiving the drug.

Who should consider this trial

Good fit: Ideal candidates are hospitalized children from birth to less than 18 years old who are receiving systemic antibiotics for known or suspected bacterial infections.

Not a fit: Patients with severe sepsis or those who do not meet the inclusion criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a new treatment option for pediatric patients suffering from serious bacterial infections, particularly those resistant to existing antibiotics.

How similar studies have performed: Other studies have shown promise in using carbapenem agents for resistant bacterial infections, but this specific combination therapy is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. A signed and dated written informed consent from the parent or legal representative and a subject assent (according to local IRB requirements);
2. Male or female from birth to \< 18 years of age;
3. Are hospitalized, in stable condition, and receiving systemic antibiotics for a known or suspected bacterial infection; or subjects receiving peri-operative prophylactic use of antibiotics;
4. The subject will be observed in the hospital for at least 6 hours after the study drug is administered;
5. If female and has reached menarche, or has reached Tanner Stage 3 breast development (even if not having reached menarche), the subject is practicing appropriate birth control or is sexually abstinent;
6. Sufficient intravascular access (peripheral or central) to receive study drug.

Subjects will be excluded from the study if any of the following exclusion criteria apply prior to randomization:

1. Signs of severe sepsis including:

   1. Shock or profound hypotension that is not responsive to fluid challenge;
   2. Hypothermia (core temperature \< 35.6 ºC or 96.1 ºF);
   3. Disseminated intravascular coagulation as evidenced by prothrombin time or partial thromboplastin time ≥ 2X the ULN or platelets \< 50% of the lower limit of normal;
2. Any surgical or medical condition which, in the opinion of the investigator, would put the subject at increased risk or is likely to interfere with study procedures or PK of the study drug;
3. Females who are of childbearing potential and unwilling to practice abstinence or use at least two methods of contraception (oral contraceptives, barrier methods, approved contraceptive implant) during the entire study period;
4. Female adolescent subjects who are pregnant or breastfeeding or have a positive serum β-hCG pregnancy test at screening and at pre-dose Day 1;
5. Males who are unwilling to practice abstinence or use an acceptable method of broth control during the entire study period (i.e. condom with spermicide);
6. Renal function at screening as estimated by creatinine clearance \< 50 mL/min /1.73 m\^2 as calculated using the updated Schwartz bedside formula: eGFR = k x (height in cm) ÷ serum creatinine

   * k = 0.33 in pre-term infants.
   * k = 0.45 in term infants to 1 year of age.
   * k = 0.55 in children and adolescent girls.
   * k = 0.70 in adolescent boys.
7. Treatment within 30 days prior to enrollment with valproic acid;
8. Treatment within 30 days prior to enrollment with probenecid;
9. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy;
10. Neutropenia with absolute neutrophil count (ANC) \< 500 cells/mm3;
11. Aspartate aminotransferase or alanine aminotransferase ≥ 3X ULN or total bilirubin ≥ 1.5X ULN;
12. Receipt of any investigational medication or investigational device within 30 days prior to enrollment;
13. Prior exposure to vaborbactam or Vabomere;
14. Use of meropenem within 48 hours of administration of study drug or 12 hours after study drug administration;
15. Known significant hypersensitivity to any beta-lactam antibiotic;
16. Unable or unwilling in the judgment of the Investigator, to comply with the protocol;
17. Subject is a child of an employee of the Investigator or study center with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member of the employee or the Investigator;
18. Body Mass Index (BMI) outside the range (below the 5th percentile or above the 95th percentile) for height, age and weight except for children \< 2 years of age.)

Where this trial is running

Little Rock, Arkansas and 9 other locations

• Arkansas Children's Hospital — Little Rock, Arkansas, United States (Completed)
• Ronald Reagan UCLA Medical Center — Los Angeles, California, United States (Recruiting)
• Children's Hospital of Orange County — Orange, California, United States (Completed)
• Rady Children's Hospital San Diego — San Diego, California, United States (Recruiting)
• Los Angeles Biomedical Research Institute — Torrance, California, United States (Withdrawn)
• Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (Recruiting)
• University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)
• Rutger's University — New Brunswick, New Jersey, United States (Completed)
• Rainbow Babies and Childrens Hospital — Cleveland, Ohio, United States (Completed)
• Toledo Children's Hospital — Toledo, Ohio, United States (Completed)

Conditions Bacterial Infections