A Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Meropenem-Vaborbactam in Children With Complicated Urinary Tract Infection, Including Acute Pyelonephritis

Rempex Pharmaceuticals

Status and phase: Enrolling; Phase 2

Conditions: Acute Pyelonephritis; Complicated Urinary Tract Infection

Treatments: Drug: Antibiotics; Drug: Meropenem-Vaborbactam

Study type: Interventional

Funder types: Industry; Other U.S. Federal agency

Identifiers

NCT06672978

2024-516360-29 (EudraCT Number)

U1111-1310-7249 (Other Identifier)

ML-VAB-201-3248-2

Details and patient eligibility

About

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)

Enrollment: 66 estimated patients

Sex: All

Ages: 3 months to 12 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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66 participants in 3 patient groups

Cohort 1: Age 6 to < 12 years

Experimental group

Description:

Participants will receive meropenem-vaborbactam via an intravenous (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 after Day 3.

Treatment:

Drug: Meropenem-Vaborbactam

Drug: Antibiotics

Cohort 2: Age 2 to < 6 years

Experimental group

Description:

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 after Day 3.

Treatment:

Drug: Meropenem-Vaborbactam

Drug: Antibiotics

Cohort 3: Age 3 months to < 2 years

Experimental group

Description:

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 after Day 3.

Treatment:

Drug: Meropenem-Vaborbactam

Drug: Antibiotics