Vabomere for Pediatric Bacterial Infections

(TANGOKIDS Trial)

Not currently recruiting at 8 trial locations

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Vabomere (Meropenem/Vaborbactam) for children with serious bacterial infections. The researchers aim to understand how the drug works in the body, determine the right dose, and assess its safety. The trial involves a single dose administered through an IV and includes various age groups, from newborns to those just under 18 years old. Hospitalized children currently receiving antibiotics for a known or suspected bacterial infection might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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 there any evidence suggesting that Vabomere is likely to be safe for pediatric patients?

Research shows that Vabomere, a combination of meropenem and vaborbactam, has been tested for safety in adults and is now under study in children. In earlier studies with adults, most participants tolerated Vabomere well, experiencing no serious side effects. However, Vabomere can cause allergic reactions in individuals sensitive to its ingredients.

The current studies in children aim to determine how their bodies process the drug and assess its safety for them. Until more information becomes available, patients should exercise caution, especially during activities requiring full attention, such as driving or operating machinery. This caution is due to potential side effects in children that remain unclear. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Vabomere is unique because it combines meropenem, a powerful antibiotic, with vaborbactam, which protects the antibiotic from being broken down by resistant bacteria. This combination makes it particularly effective against tough bacterial infections that don't respond well to standard treatments like amoxicillin or cephalosporins. Researchers are excited about Vabomere because its innovative formula could significantly improve treatment outcomes for pediatric patients, offering a potential breakthrough for those with limited options. Additionally, its administration as a single IV dose over three hours could streamline treatment, making it more convenient for both patients and healthcare providers.

What evidence suggests that Vabomere might be an effective treatment for pediatric bacterial infections?

Research has shown that Vabomere, a combination of meropenem and vaborbactam, effectively and safely treats serious bacterial infections in children. In previous cases, children successfully recovered from infections using this treatment. This combination works particularly well against certain difficult-to-treat bacteria known as Gram-negative bacteria. Studies indicate that Vabomere has a high success rate of about 98.4% compared to other antibiotics like piperacillin/tazobactam. This trial will evaluate Vabomere's effectiveness across different pediatric age groups, suggesting it could be a strong option for treating bacterial infections in children. ^{6 7 8 9 10}

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 (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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12288576/

Meropenem/Vaborbactam in Pediatrics: 2 Cases of CRE ... These cases demonstrate the safe and effective use of meropenem/vaborbactam in these 2 pediatric patients. Although meropenem/vaborbactam successfully treated ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02687906

Dose-finding, Pharmacokinetics, and Safety of VABOMERE ... This study is an open label, dose-finding, pharmacokinetics, safety, and tolerability study of a single dose infusion of meropenem-vaborbactam in pediatric ...

3. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bcp.16145

Dose rationale for the use of meropenem/vaborbactam ... Dose rationale for the use of meropenem/vaborbactam combination in paediatric patients with Gram-negative bacterial infections · DATA ...

4. academic.oup.com academic.oup.com/ofid/article/10/Supplement_2/ofad500.1509/7446669

1676. PK, Safety and Tolerability of VABOMERE ... The PK, safety, and efficacy data of MV in adults support study in pediatrics. Methods. Phase 1, open-label, dose-finding study. Pediatric ...

5. vabomere.com vabomere.com/clinical-data.html

VABOMERE (meropenem and vaborbactam) ǀ Clinical ... VABOMERE (meropenem and vaborbactam) demonstrated an overall success rate of 98.4% vs 94.3% with piperacillin/tazobactam.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10677301/

1676. PK, Safety and Tolerability of VABOMERE® ... The PK, safety, and efficacy data of MV in adults support study in pediatrics. Methods. Phase 1, open-label, dose-finding study. Pediatric ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02687906

Dose-finding, Pharmacokinetics, and Safety of VABOMERE ... This study is an open label, dose-finding, pharmacokinetics, safety, and tolerability study of a single dose infusion of meropenem-vaborbactam in pediatric ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2017/209776lbl.pdf

VABOMERE (meropenem and vaborbactam) for injection Until it is reasonably well established that VABOMERE is well tolerated, advise patients not to operate machinery or motorized vehicles [see Adverse Reactions.

9. vabomere.com vabomere.com/isi.html

VABOMERE (meropenem and vaborbactam) ǀ isi IMPORTANT SAFETY INFORMATION. Contraindications. VABOMERE is contraindicated in patients with known hypersensitivity to any components of VABOMERE ...

10. ec.europa.eu ec.europa.eu/health/documents/community-register/2018/20181120142682/anx_142682_en.pdf

Vabomere, INN-meropenem/vaborbactam What Vabomere is used for. Vabomere is used in adults to treat certain serious bacterial infections: • of the bladder or kidneys (urinary tract infections).