Approval Probability
TA Base Rate
Adjusted LOA
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Also known as Vabomere, Carbavance, Meropenem 2 g-Vaborbactam 2 g
Meropenem-Vaborbactam · 4 trials · 8 indications
This was the primary outcome measure for the Food and Drug Administration (FDA). For this composite outcome measure, overall success was achieved with a clinical outcome of Cure or Improvement and microbiologic outcome of Eradication at the end of intravenous treatment (EOIVT). Cure was defined as the complete resolution or significant improvement of the baseline signs and symptoms. Improvement was defined as lessening, incomplete resolution, or no worsening of the baseline signs and symptoms. Eradication was defined using the FDA's colony-forming units (CFU)/mL criteria that the bacterial pathogen(s) found at baseline was/were reduced to \<10\^4 CFU/mL of urine culture and a negative blood culture for an organism that was identified as an uropathogen (if repeated after positive at baseline blood culture).
This was the primary outcome measure for the European Medicines Agency (EMA). For this measure, a microbiologic outcome of Eradication was defined using the EMA's CFU/mL criteria: bacterial pathogen(s) found at baseline was reduced to \<10\^3 CFU/mL of urine culture and a negative blood culture for an organism that was identified as an uropathogen (if repeated after positive at baseline blood culture).
This was the primary outcome measure for the EMA. For this measure, a microbiologic outcome of Eradication was defined using the EMA's CFU/mL criteria: bacterial pathogen(s) found at baseline was reduced to \<10\^3 CFU/mL of urine culture and a negative blood culture for an organism that was identified as an uropathogen (if repeated after positive at baseline blood culture). The ME population included all participants who met m-MITT criteria and had a clinical outcome and microbiologic outcome at EOIVT or earlier; received \<80% or \>120% of expected IV doses; missed no more than 1 IV dose in the first 48 hours, missed no more than 2 consecutive IV doses; received no less than 6 doses for failure or no less than 9 doses for cure.
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.
The All-cause mortality rate at Day 28 in the mCRE-MITT population (HABP/VABP and Bacteremia)
Clinical cure defined as complete resolution or significant improvement of the baseline signs and symptoms, no further antimicrobial warranted.
AUC from time zero to infinity
maximum measured plasma concentration
time to Cmax
total body clearance
elimination half- life
minimum plasma concentration
Volume of distribution
a composite measure of the number and types of AEs/SAEs encountered and relationship to time of dosing
A composite measure of multiple laboratory results assessing the clinical significance of any changes from baseline
A composite of multiple vital sign measurements, assessing the clinical significance of any changes from baseline
A composite of multiple ECG measurements, assessing the clinical significance of any changes from baseline
| Arm | Type | Description |
|---|---|---|
| Meropenem-Vaborbactam | EXPERIMENTAL | Meropenem-vaborbactam (meropenem 2 grams \[g\] plus vaborbactam 2 g), infused in 250 milliliters (mL) normal saline, administered intravenously (IV) over 3 hours, every 8 hours (q8h), with 100 mL saline administered over 30 minutes q8h. Levofloxacin tablets administered orally as a 500-milligram (mg) dose every 24 hours (q24h) after a minimum of 15 doses of IV meropenem-vaborbactam plus saline, if clinically indicated. Total treatment was 10 days, unless a participant had baseline bacteremia where up to 14 days of therapy could be administered IV. |
| Piperacillin-Tazobactam | ACTIVE_COMPARATOR | Piperacillin-tazobactam (piperacillin 4 g plus tazobactam 0.5 g), infused in 100 mL normal saline, administered IV over 30 minutes, q8h, with 250 mL saline administered over 30 minutes q8h. Levofloxacin tablets administered orally as a 500-mg dose q24h after a minimum of 15 doses of IV piperacillin-tazobactam plus saline, if clinically indicated. Total treatment was 10 days, unless a participant had baseline bacteremia where up to 14 days of therapy could be administered IV. |
| Vabomere | EXPERIMENTAL | Vabomere (meropenem 2g plus vaborbactam 2g) IV q8h, for up to 14 days |
| Best Available Therapy | ACTIVE_COMPARATOR | Subjects will receive Best Available Therapy (IV antibiotics) |
| Cohort 1: Age 6 to < 12 years | EXPERIMENTAL | Participants will receive meropenem-vaborbactam via an IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic or home IV therapy after Day 3. |
| Cohort 2: Age 2 to < 6 years | EXPERIMENTAL | Participants will receive meropenem-vaborbactam IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic or home IV therapy after Day 3. |
| Cohort 3: Age 3 months to < 2 years | EXPERIMENTAL | Participants will receive meropenem-vaborbactam IV infusion for a minimum of 3 days, for up to 14 days. Participants with clinical improvement have the option to switch to an oral antibiotic or home IV therapy after Day 3. |
| Single dose IV meropenem-vaborbactam | EXPERIMENTAL | 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) |
| Name | Type | Description |
|---|---|---|
| Meropenem-Vaborbactam | DRUG | Meropenem-vaborbactam |
| Piperacillin-Tazobactam | DRUG | Piperacillin-tazobactam |
| Levofloxacin | DRUG | Levofloxacin |
| Saline | DRUG | Saline |
| Vabomere | DRUG | Vabomere for IV injection, administered as a 2 g/2 g dose |
| Best Available Therapy | DRUG | Antibiotic(s) chosen by Investigator |
| Antibiotics | DRUG | Administered as prescribed by the study physician in accordance with local guidelines and regulations. |
Inclusion Criteria: 1. A signed informed consent form, the ability to understand the study conduct and tasks that are required for study participation, and a willingness to cooperate with all tasks, tests, and examinations as required by the protocol. 2. Male or female ≥18 years of age. 3. Weight ≤...
Meropenem-vaborbactam is used to treat serious bacterial infections, including complicated urinary tract infection, acute pyelonephritis, hospital acquired bacterial pneumonia, ventilator-associated bacterial pneumonia, bacteremia, and abdominal infection. It is being studied in adults and in children as young as 3 months with complicated urinary tract infection or acute pyelonephritis.
Meropenem-vaborbactam targets penicillin-binding proteins (PBP) and Klebsiella pneumoniae carbapenemase (KPC). Meropenem is the antibacterial component that binds penicillin-binding proteins, while vaborbactam is a beta-lactamase inhibitor that acts on KPC enzymes. This combination is designed to address bacterial infections where KPC beta-lactamase activity would otherwise compromise the antibacterial component.
Meropenem-vaborbactam is being developed by CorMedix Inc., which trades on the Nasdaq under the ticker CRMD. The company is the sponsor of the pediatric clinical program evaluating the combination in children with complicated urinary tract infection and acute pyelonephritis.
Meropenem-vaborbactam is in Phase 2 development for its pediatric program in complicated urinary tract infection and acute pyelonephritis. Earlier studies include a completed Phase 1 pediatric trial and completed Phase 3 trials in adults. It is an investigational product in the studies described here and is not described as approved in this program.
The active trial is NCT06672978, a Phase 2 study of safety, tolerability, and pharmacokinetics in children with complicated urinary tract infection, including acute pyelonephritis, in the United States, Bulgaria, Croatia, Georgia, Greece, and Poland. Completed studies include NCT02687906, a Phase 1 pediatric trial, and the Phase 3 trials NCT02168946 and NCT02166476.
Yes, meropenem-vaborbactam is also known as Vabomere. Vabomere is the brand name used for the combination in its clinical trial titles, including the Phase 1 pediatric study NCT02687906 and the Phase 3 adult study NCT02168946. Searches for either name refer to the same meropenem and vaborbactam combination product.