Dose-finding, Pharmacokinetics, and Safety of VABOMERE in Pediatric Subjects With Bacterial Infections

NCT ID: NCT02687906

Last Updated: 2025-07-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-07-31
• Study Completion Date: 2025-12-31

Brief Summary

A single dose infusion of Vabomere (meropenem-vaborbactam) is being tested for dose-finding, pharmacokinetics, safety, and tolerability in pediatric subjects from birth to less than 18 years of age with serious bacterial infections

Detailed Description

In the current era of increased resistance to extended spectrum cephalosporins, carbapenem antimicrobial agents are frequently the antibiotics of "last defense" for the most resistant pathogens in serious infections, including those found in complicated Urinary Tract Infections (cUTI). The recent dissemination of serine carbapenemases (e.g. KPC) in Enterobacteriaceae in many hospitals worldwide now poses a considerable threat to the carbapenems and other members of the beta-lactam class of antimicrobial agents.

Rempex developed meropenem-vaborbactam administered as a fixed combination by IV infusion, to treat serious Gram-negative infections, such as cUTIs, including those infections caused by bacteria resistant to currently available carbapenems.

This study is an open label, dose-finding, pharmacokinetics, safety, and tolerability study of a single dose infusion of meropenem-vaborbactam in pediatric subjects from birth to less than 18 years of age with suspected or confirmed bacterial infection receiving antibiotic therapy or subjects receiving peri-operative prophylactic use of antibiotics.

Conditions

Bacterial Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single dose IV meropenem-vaborbactam

Vabomere (meropenem-vaborbactam) for IV injection will be administered as a single dose diluted in normal saline infused IV over 3 hours

• Cohort 1 (n=8): 12 to < 18 years of age (40 mg/kg)
• Cohort 2 (n=8): 6 to < 12 years of age (40 mg/kg)
• Cohort 2b (n=4): 6 to < 12 years of age (60 mg/kg)
• Cohort 3 (n=8): 2 to < 6 years of age (60 mg/kg)
• Cohort 4 (n=8): 3 months to < 2 years of age (60 mg/kg)
• Cohort 5 (n=24): Birth to < 3 months of age (dose TBD)

• Group A: Gestational Age (GA) < 32 weeks, Postnatal Age (PNA) < 2 weeks (n=6)
• Group B: GA < 32 weeks, PNA > 2 weeks (n=6)
• Group C: GA > 32 weeks, PNA < 2 weeks (n=6)
• Group D: GA > 32 weeks, PNA > 2 weeks (n=6)
• Cohort 6 (n=7): 2 to < 12 years of age and ≤ 35 kg of weight (80 mg/kg)

Group Type: EXPERIMENTAL

Vabomere

Intervention Type: DRUG

Vabomere (meropenem-vaborbactam) for IV injection

Interventions

Vabomere

Vabomere (meropenem-vaborbactam) for IV injection

Intervention Type: DRUG

Other Intervention Names

Combination meropenem and vaborbactam; carbapenem and beta-lactamase inhibitor

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.

Exclusion Criteria

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.)

• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Department of Health and Human Services

FED

Sponsor Role: collaborator

Rempex (a wholly owned subsidiary of Melinta Therapeutics, LLC)

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Melinta Therapeutics, Inc.

Locations

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Ronald Reagan UCLA Medical Center

Los Angeles, California, United States

Children's Hospital of Orange County

Orange, California, United States

Rady Children's Hospital San Diego

San Diego, California, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Rutger's University

New Brunswick, New Jersey, United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Toledo Children's Hospital

Toledo, Ohio, United States

Countries

United States

References

Bradley JS, Harvey H, Stout D, Momper J, Capparelli E, Avedissian SN, Barbato C, Mak RH, Jones TP, Jones D, Le J. Subtherapeutic Meropenem Antibiotic Exposure in Children With Septic Shock Assessed by Noncompartmental Pharmacokinetic Analysis in a Prospective Dataset. Pediatr Crit Care Med. 2025 Apr 1;26(4):e507-e515. doi: 10.1097/PCC.0000000000003698. Epub 2025 Feb 18.

Reference Type: DERIVED

PMID: 39964222 (View on PubMed)

Other Identifiers

2016-000656-99

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

Rempex 507

Identifier Type: -

Identifier Source: org_study_id