meropenem; vaborbactam for Gram-negative bacterial infections | Complicated urinary tract infection | Acute pyelonephritis

Inclusion criteria

• {"criterion_text":"- Written informed consent before initiation of any study-related procedures. Parent or legal representative has given informed consent, as appropriate, and the participant has given assent where appropriate."}
• {"criterion_text":"- Male or female, from birth to < 18 years of age. Participants aged < 3 months are eligible if gestational age at birth is > 32 weeks."}
• {"criterion_text":"- Require hospitalization and a minimum of 3 days of IV antibiotic treatment for suspected or confirmed Gram negative infection as per Investigator’s judgement."}
• {"criterion_text":"- Confirmed or suspected Gram negative infection, according to the diagnostic criteria reported in APPENDIX 1 for participants aged 3 months < 18 years and in APPENDIX 2 for participants < 3 months of age."}

Exclusion criteria

• {"criterion_text":"- History of any moderate or significant hypersensitivity or allergic reaction to betalactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams)."}
• {"criterion_text":"- Renal function at screening as estimated by creatinine clearance <50 mL/min/1.73m2 (<30 mL/min/1.73 m2 in participants aged < 3 months) using the Schwartz eGFR formula."}
• {"criterion_text":"- Presence of any condition reported as exclusion criteria in Appendix 1 and Appendix 2."}
• {"criterion_text":"- Anticipated need for antibacterial therapy longer than 14 days."}
• {"criterion_text":"- Endocarditis, osteomyelitis, abscess, meningitis, C. difficile infection diagnosed within 7 days prior to start of treatment."}
• {"criterion_text":"- On treatment or expected to receive immunosuppressive agents, valproic acid or probenecid."}
• {"criterion_text":"- Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy"}
• {"criterion_text":"- Presence of immunodeficiency or an immunocompromised condition including hematologic malignancy, bone marrow transplant, or receiving immunosuppressive therapy such as cancer chemotherapy, medications for the rejection of transplantation, and long-term use of systemic corticosteroids (equivalent to >2mg/kg/day for more than 1 week or > 1mg/kg/day in participants under 20kg for more than 14 days of prednisone or systemic equivalent.)."}
• {"criterion_text":"- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × ULN, or total bilirubin >1.5 × ULN (except for known Gilbert’s disease)."}
• {"criterion_text":"- Receipt of any investigational medication or investigational device during the last 30 days prior to start of treatment and until the End of Study visit."}
• {"criterion_text":"- Requirement at time of enrollment, for any reason, for additional systemic antibiotic therapy (other than study drug) or antifungal therapy."}
• {"criterion_text":"- Unable or unwilling, in the judgement of the Investigator, to comply with the protocol or complete the clinical study."}
• {"criterion_text":"- Known history of human immunodeficiency virus (HIV) infection with a CD4 count <200/mm3 or, in children aged <5 years, CD4% <15%."}
• {"criterion_text":"- Presence of neutropenia (<500 polymorphonuclear leukocytes- PMNs/mm3) unless justified by the investigated infection as per Investigator’s judgement."}
• {"criterion_text":"- Presence of thrombocytopenia (<60,000 platelets/mm3)."}
• {"criterion_text":"- Presence of severe anemia (Hb < 8 g/dL)"}
• {"criterion_text":"- Is or has an immediate family member of the Investigator or Site staff directly involved in the proposed study."}
• {"criterion_text":"- Receipt of an antibacterial drug for the investigated Gram negative infection for a continuous duration of more than 24 hours during the previous 72 hours. Exceptions apply to: a. participants who have received >48 hours of prior systemic antibiotic therapy for the investigated infection with unequivocal clinical or microbiological evidence of treatment failure (i.e., worsening of signs and symptoms); b. participants who have received antimicrobial prophylaxis or who have received antibiotics for another indication and have developed signs and symptoms of investigated infection."}
• {"criterion_text":"- Participants with a concurrent infection requiring additional systemic antimicrobial treatment."}
• {"criterion_text":"- Any surgical or medical condition which, in the opinion of the Investigator, would put the participant at increased risk (e.g. unlikely to survive to the study period, or with rapidly progressive illness including septic shock) or is likely to interfere with study procedures or PK of the study drug."}
• {"criterion_text":"- Females who are of childbearing potential (i.e. fertile, following menarche unless permanently sterile due to hysterectomy, bilateral salpingectomy and bilateral oophorectomy) and unwilling to practice abstinence or use at least two methods of contraception (see APPENDIX 3 - BIRTH CONTROL METHODS APPLICABLE IN VABOR-KIDS-01 STUDY) during the entire study period and up to 28 days after VaboremⓇ discontinuation."}
• {"criterion_text":"- Pregnant or breastfeeding female adolescent participants or a positive serum β human chorionic gonadotropin (hCG) pregnancy test at Screening."}
• {"criterion_text":"- Male adolescents who are unwilling to practice abstinence or use an acceptable method of birth control during the entire study period (i.e. condom with spermicide)."}

Primary endpoints

• {"endpoint_text":"- Individual PK parameters derived with updated popPK models: Area under the concentrationtime curve (AUC), maximum plasma concentration (Cmax), time to maximum plasma concentration (Tmax), drug clearance (CL), half-life (t1/2), minimum plasma concentration (Cmin), and steady-state volume of distribution (Vss).","definition_or_measurement_approach":"PK parameters derived using updated population PK (popPK) models; sampling includes PK session on Day 3 with blood samples and parameter estimation (AUC, Cmax, Tmax, CL, t1/2, Cmin, Vss) using meropenem and vaborbactam popPK models updated with paediatric data."}

Secondary endpoints

• {"endpoint_text":"- Adverse Events (AEs), serious AEs (SAEs), and AE of special interest (AESI), as well as changes in clinical laboratory values, and vital signs following VaboremⓇ administration versus baseline.","definition_or_measurement_approach":"Safety monitoring of AEs/SAEs/AESIs and assessment of changes from baseline in clinical laboratory values and vital signs following administration of Vaborem®."}

Poland

Earliest CTIS Part Ii Submission Date

12-12-2024

Latest Decision Or Authorization Date

12-09-2025

Processing Time Days

274

Number Of Sites

3

Number Of Participants

6

Italy

Earliest CTIS Part Ii Submission Date

25-11-2024

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

289

Number Of Sites

6

Number Of Participants

13

Spain

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

289

Number Of Sites

6

Number Of Participants

13

France

Earliest CTIS Part Ii Submission Date

14-11-2024

Latest Decision Or Authorization Date

11-09-2025

Processing Time Days

301

Number Of Sites

5

Number Of Participants

8

Czechia

Earliest CTIS Part Ii Submission Date

26-11-2024

Latest Decision Or Authorization Date

10-09-2025

Processing Time Days

288

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Menarini Ricerche S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

Phlexglobal Limited

Responsibilities

eTMF

Name

Almac Clinical Services Limited

Responsibilities

secondary packaging labelling, and QP certification of IMP.

Name

LINICAL Europe GmbH

Responsibilities

multiple study operations and site payment responsibilities (sponsorDuties entries: 1,11,12,13,15 (Sites payment),2,5,8,9)

Name

Calyx

Responsibilities

data services (sponsorDuties code:3)

Name

Medidata Solutions Inc.

Responsibilities

clinical data platform / role (sponsorDuties code:7)

Third parties

• {"country":"United Kingdom","full_name":"Phlexglobal Limited","duties_or_roles":"eTMF","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"Pk analysis","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Site Payment and patient reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Almac Clinical Services Limited","duties_or_roles":"secondary packaging labelling, and QP certification of IMP.","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"code:7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Belgium","full_name":"Cerba Research","duties_or_roles":"PK sample handling and storage","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United Kingdom","full_name":"Calyx","duties_or_roles":"code:3","organisation_type":"Industry"}
• {"country":"Germany","full_name":"LINICAL Europe GmbH","duties_or_roles":"codes:1,11,12,13,15 (Sites payment),2,5,8,9","organisation_type":"Pharmaceutical company"}