Clinical trial NCT06672978: A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Meropenem-Vaborbactam in Children With Complicated Urinary Tract Infection, Including Acute Pyelonephritis
Official title: A Multi-Center, Open-Label, Single-Arm, Phase 2 Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of Vabomere (Meropenem-Vaborbactam) In The Treatment Of Children With Complicated Urinary Tract Infection, Including Acute Pyelonephritis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Acute Pyelonephritis
Complicated Urinary Tract Infection
Lead sponsor: Melinta Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Biomedical Advanced Research and Development Authority
First posted: 2024-11-04
Enrollment: 66
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to assess the safety and tolerability of meropenem-vaborbactam administered by intravenous (IV) infusion in children 3 months and above to less than 12 years with complicated urinary tract infections (cUTI), including acute pyelonephritis (AP)


Eligibility criteria: Key Inclusion Criteria:

* Have a clinically suspected and/or bacteriologically documented cUTI or AP judged by the Investigator to require hospitalization for treatment with at least 3 days of IV antibiotics.
* Evidence of pyuria, confirmed by either of the following:

  * A urine specimen that is positive for leukocyte esterase via urine dipstick or urinalysis, or
  * A urine specimen with either \> 10 white blood cells (WBCs) per microliter from an unspun urine or \> 5WBCs per high power field from a centrifuged specimen
* Symptomatic or asymptomatic cUTI or AP as specified in the protocol.

  * Acute Pyelonephritis (qualifying symptoms specified in protocol)
* Have a pretreatment "baseline" urine specimen obtained for culture by an acceptable method, including suprapubic aspiration (SPA), clean urethral catheterization, in dwelling urethral catheter, or mid-stream clean catch (urine specimens obtained from externally placed urine bags will not be allowed) within 48 hours before the start of the administration of the first dose of IV study drug therapy.
* Must, based on the judgment of the Investigator, require hospitalization initially and 7 to14 days of antibacterial therapy for the treatment of the presumed cUTI.

Key Exclusion Criteria:

* History of hypersensitivity or allergic reaction to beta-lactam antibiotics (for example \[e.g.\],cephalosporins, penicillins, carbapenems, monobactams).
* Known Vabomere-resistant gram-negative organism from study-qualifying urine or blood culture, confirmed cUTI or AP only due to gram-positive organism from study-qualifying urine or blood culture, or known or suspected infection with organisms that are not adequately covered by Vabomere (e.g., viral, mycobacterial, fungal).
* Receipt of a potentially effective antibacterial drug therapy for cUTI for a duration of more than 24 hours during the previous 72 hours prior to enrollment. Exceptions: participants with unequivocal clinical evidence of treatment failure (that is, worsening signs and symptoms); urine culture confirms resistance to the initial antibiotic; or the participant developed signs and symptoms of cUTI or AP while on antibiotics for another indication.
* Participants undergoing dialysis or with estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m\^2, as calculated using the updated bedside Schwartz formula.
* Evidence of significant hepatic disease or dysfunction, including known acute viral or inactive chronic hepatitis or hepatic encephalopathy, or aspartate aminotransferase or alanine aminotransferase \> 3 × upper limit normal (ULN), or total bilirubin \> 1.5 × ULN.

Note: Other protocol-defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to 28 days
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax)
timeFrame: Day 1 and Day 3: Up to 3 hours post-dose
measure: Time to Maximum Observed Plasma Concentration (Tmax)
timeFrame: Day 1 and Day 3: Up to 3 hours post-dose
measure: Area Under the Plasma Concentration Curve From Zero to infinity (AUC0-inf)
timeFrame: Day 1 and Day 3: Up to 3 hours post-dose
measure: Overall Response (OR)
timeFrame: Up to 14 days
measure: Clinical Cure
timeFrame: Up to 14 days
measure: Favorable Microbiological Response (Microbiological Eradication)
timeFrame: Up to 14 days
Other outcomes:
Locations:
city: Orange
country: United States
facility: Children's Hospital of Orange County
state: California
city: Plovdiv
country: Bulgaria
facility: University Multipurpose Hospital for Active Treatment "Sveti Georgi", Pediatrics Clinic
city: Ruse
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment 'Kanev', Ruse, Department of Pediatrics
city: Sliven
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment "Dr. Ivan Seliminski", Sliven
city: Sofia
country: Bulgaria
facility: Multiprofile Hospital For Active Treatment, "Vita", Department of Urology
city: Sofia
country: Bulgaria
facility: University Hospital for Active Treatment and Emergency Medicine (UHATEM) "N. I. Pirogov" LTD, Urology Clinic, Department of Urology
Study officials:
affiliation: Melinta Therapeutics, LLC
name: Medical Information
role: STUDY_DIRECTOR
References: