Vabomere for Pediatric Bacterial Infections

(TANGOKIDS Trial)

Recruiting at 1 trial location

Overseen By William Waverczak, MS

Age: < 18

Sex: Any

Trial Phase: Phase 1

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

Must be taking: Systemic antibiotics

Must not be taking: Valproic acid, Probenecid

Disqualifiers: Severe sepsis, Renal dysfunction, Hepatic disease, Neutropenia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

67 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

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

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have taken valproic acid or probenecid within 30 days before joining. Also, you should not have used meropenem within 48 hours before or 12 hours after the study drug is given.

Is Vabomere safe for use in humans?

Meropenem-vaborbactam (Vabomere) has been shown to be generally safe and well tolerated in clinical trials, with no serious adverse events reported in healthy adult subjects. It has favorable safety profiles compared to other antibiotics for resistant infections. ^{1 2 3 4 5}

What makes the drug Vabomere unique for treating bacterial infections in children?

Vabomere is unique because it combines meropenem, a powerful antibiotic, with vaborbactam, a novel substance that blocks enzymes (beta-lactamases) that make bacteria resistant to antibiotics. This combination is particularly effective against tough-to-treat bacteria like Klebsiella pneumoniae, which are resistant to many other antibiotics. ^{1 5 6 7 8}

Who Is on the Research Team?

Study Director

Principal Investigator

Melinta Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for hospitalized children from birth to under 18 years with serious bacterial infections or needing peri-operative antibiotics. They must have stable vital signs, appropriate intravascular access, and not be at high risk of complications as judged by the investigator. Females in puberty must use birth control or abstain sexually; males also need to practice safe sex.

Inclusion Criteria

I have a working IV line for receiving the study drug.

A signed and dated written informed consent from the parent or legal representative and a subject assent (according to local IRB requirements)

I am under 18 years old.

Exclusion Criteria

Receipt of any investigational medication or investigational device within 30 days prior to enrollment

Known significant hypersensitivity to any beta-lactam antibiotic

I do not have severe liver disease or symptoms like confusion due to liver problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive a single dose infusion of Vabomere (meropenem-vaborbactam) administered as a fixed combination by IV infusion

1 day

1 visit (in-person)

Pharmacokinetics Monitoring

Pharmacokinetics parameters such as Tmax, Cmax, drug clearance, and others are measured

6 hours

Safety Follow-up

Participants are monitored for safety and tolerability, including clinical safety laboratory results, vital signs, ECGs, and AEs/SAEs

7 days

What Are the Treatments Tested in This Trial?

Interventions

• Vabomere

Trial Overview The study tests a single infusion dose of Vabomere (meropenem-vaborbactam) in young patients. It aims to find the right dosage, understand how the drug works in their bodies (pharmacokinetics), and assess its safety and tolerability.

How Is the Trial Designed?

Group I: Single dose IV meropenem-vaborbactam Experimental Treatment 1 Intervention

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)

Vabomere is already approved in United States for the following indications:

Approved in United States as Vabomere for:

• Complicated urinary tract infections
• Complicated abdominal infections
• Hospital-acquired pneumonia

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

2

Recruited

130+

Rempex (a wholly owned subsidiary of Melinta Therapeutics, Inc.)

Lead Sponsor

Trials

7

Recruited

600+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

Published Research Related to This Trial

Meropenem-vaborbactam is effective against complicated urinary tract infections and acute pyelonephritis caused by carbapenem-resistant Enterobacteriaceae, as shown in the Phase III trial TANGO I.

The drug is safe, well tolerated, and has better pharmacokinetic and pharmacodynamic profiles compared to other antibiotics targeting the same resistant bacteria, making it a valuable option for treating infections caused by K. pneumoniae carbapenemase-producing CRE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem-vaborbactam: a new weapon in the war against infections due to resistant Gram-negative bacteria. Patel, TS., Pogue, JM., Mills, JP., et al.[2019]

Vaborbactam, when combined with meropenem, significantly enhances the effectiveness against carbapenem-resistant Enterobacterales, particularly those producing KPC enzymes, as shown in multiple in vitro studies involving various clinical isolates.

While meropenem-vaborbactam is potent against KPC-producing bacteria, it is not effective against OXA-48 or metallo-beta lactamases, highlighting the need for targeted treatment strategies in antibiotic-resistant infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microbiology of Meropenem-Vaborbactam: A Novel Carbapenem Beta-Lactamase Inhibitor Combination for Carbapenem-Resistant Enterobacterales Infections. Bhowmick, T., Weinstein, MP.[2021]

Meropenem-vaborbactam is effective against Gram-negative bacteria, particularly those with class A serine carbapenemases like KPC, making it a crucial option for treating resistant infections.

A quality control study established standardized testing methods for meropenem-vaborbactam, ensuring reliable assessment of its efficacy against KPC-producing strains of Klebsiella pneumoniae.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determination of MIC and disk diffusion quality control guidelines for meropenem-vaborbactam, a novel carbapenem/boronic acid β-lactamase inhibitor combination. Munson, E., Huband, MD., Castanheira, M., et al.[2018]

In a study involving 76 healthy adults, the combination of meropenem and vaborbactam was found to be safe and well-tolerated, with no serious adverse events reported, indicating a favorable safety profile for this treatment.

The pharmacokinetics of meropenem and vaborbactam were similar whether administered alone or together, showing no drug-drug interactions, which supports the potential for effective use against drug-resistant Gram-negative infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects. Rubino, CM., Bhavnani, SM., Loutit, JS., et al.[2019]

Meropenem-Vaborbactam (Vabomere) is effective against infections caused by carbapenem-resistant Enterobacteriaceae, showing promising results in clinical settings.

The combination of Meropenem and Vaborbactam enhances the efficacy of treatment by overcoming resistance mechanisms, making it a valuable option for patients with limited antibiotic choices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem-Vaborbactam (Vabomere&#8482;): Another Option for Carbapenem-Resistant Enterobacteriaceae. Lee, Y., Kim, J., Trinh, S.[2020]

The combination of meropenem and vaborbactam (Vabomere) has shown strong effectiveness against Gram-negative bacteria, particularly KPC-producing, carbapenem-resistant Enterobacteriaceae, in a murine pyelonephritis model.

This combination therapy significantly enhanced bacterial killing compared to untreated controls, indicating its potential utility for treating complicated urinary tract infections caused by these resistant pathogens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in a Murine Model of Pyelonephritis. Weiss, WJ., Pulse, ME., Nguyen, P., et al.[2019]

Intravenous meropenem/vaborbactam is the first approved carbapenem/β-lactamase inhibitor combination in the USA, effectively restoring meropenem's activity against resistant Enterobacteriaceae, particularly KPC-producing strains.

In the phase 3 TANGO I trial involving patients with complicated urinary tract infections, meropenem/vaborbactam was found to be noninferior and subsequently superior to piperacillin/tazobactam for overall treatment success, with a tolerability profile similar to that of piperacillin/tazobactam.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem/Vaborbactam: A Review in Complicated Urinary Tract Infections. Dhillon, S.[2023]

Vaborbactam (VAB) is a novel beta-lactamase inhibitor that, when combined with meropenem, effectively restores its activity against Klebsiella pneumoniae carbapenemases (KPC), showing promise in treating complicated urinary tract infections caused by carbapenem-resistant Enterobacteriaceae (CRE).

Phase 1 studies indicate that VAB is well tolerated at doses up to 2000 mg, with a safety profile similar to that of meropenem alone, suggesting it could be a safe option for patients with serious infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem-resistant Enterobacteriaceae. Jorgensen, SCJ., Rybak, MJ.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Meropenem-vaborbactam: a new weapon in the war against infections due to resistant Gram-negative bacteria. [2019]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Microbiology of Meropenem-Vaborbactam: A Novel Carbapenem Beta-Lactamase Inhibitor Combination for Carbapenem-Resistant Enterobacterales Infections. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Determination of MIC and disk diffusion quality control guidelines for meropenem-vaborbactam, a novel carbapenem/boronic acid β-lactamase inhibitor combination. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam and Meropenem Alone and in Combination following Single and Multiple Doses in Healthy Adult Subjects. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Meropenem-Vaborbactam (Vabomere&#8482;): Another Option for Carbapenem-Resistant Enterobacteriaceae. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Activity of Meropenem-Vaborbactam against Carbapenem-Resistant Enterobacteriaceae in a Murine Model of Pyelonephritis. [2019]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Meropenem/Vaborbactam: A Review in Complicated Urinary Tract Infections. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Meropenem and Vaborbactam: Stepping up the Battle against Carbapenem-resistant Enterobacteriaceae. [2022]