A study to assess how Vaborem® is taking up in the body and tolerated in paediatric patients with serious infections.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Menarini Ricerche S.p.A.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

23 Jan 2025 → ongoing

Decision date (initial)

2025-01-09

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

MENARINI RICERCHE S.p.A.

External identifiers

EU CT number

2024-514656-32-00

ClinicalTrials.gov

NCT06828848

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Pharmacokinetic, Safety

To assess the PK of meropenem and vaborbactam following multiple IV infusion doses of VaboremⓇ to paediatric participants from birth to <18 years with suspected or confirmed Gram negative infections.

Secondary objectives 1

1. To assess the safety and tolerability of multiple IV- infusion doses of VaboremⓇ in paediatric participants from birth to < 18 years.

Conditions and MedDRA coding

Suspected or confirmed Gram negative infections

Study design 1 period

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001731-PIP01-14

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. 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.
2. Male or female, from birth to < 18 years of age. Participants aged < 3 months are eligible if gestational age at birth is > 32 weeks.
3. Require hospitalization and a minimum of 3 days of IV antibiotic treatment for suspected or confirmed Gram negative infection as per Investigator’s judgement.
4. 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 23

1. History of any moderate or significant hypersensitivity or allergic reaction to betalactam antibiotics (e.g., cephalosporins, penicillins, carbapenems, or monobactams).
2. Unable or unwilling, in the judgement of the Investigator, to comply with the protocol or complete the clinical study.
3. Is or has an immediate family member of the Investigator or Site staff directly involved in the proposed study.
4. 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.
5. Participants with a concurrent infection requiring additional systemic antimicrobial treatment.
6. 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.
7. 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.
8. Pregnant or breastfeeding female adolescent participants or a positive serum β human chorionic gonadotropin (hCG) pregnancy test at Screening.
9. 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).
10. 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.
11. Presence of any condition reported as exclusion criteria in Appendix 1 and Appendix 2.
12. Anticipated need for antibacterial therapy longer than 14 days.
13. Endocarditis, osteomyelitis, abscess, meningitis, C. difficile infection diagnosed within 7 days prior to start of treatment.
14. On treatment or expected to receive immunosuppressive agents, valproic acid or probenecid.
15. Evidence of significant hepatic disease or dysfunction, including known acute viral hepatitis or hepatic encephalopathy
16. 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.).
17. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × ULN, or total bilirubin >1.5 × ULN (except for known Gilbert’s disease).
18. 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.
19. Requirement at time of enrollment, for any reason, for additional systemic antibiotic therapy (other than study drug) or antifungal therapy.
20. Known history of human immunodeficiency virus (HIV) infection with a CD4 count <200/mm3 or, in children aged <5 years, CD4% <15%.
21. Presence of neutropenia (<500 polymorphonuclear leukocytes- PMNs/mm3) unless justified by the investigated infection as per Investigator’s judgement.
22. Presence of thrombocytopenia (<60,000 platelets/mm3).
23. Presence of severe anemia (Hb < 8 g/dL)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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).

Secondary endpoints 1

1. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Menarini Ricerche S.p.A.

Sponsor organisation

Menarini Ricerche S.p.A.

Address

Via Dei Sette Santi 1

City

Florence

Postcode

50131

Country

Italy

Scientific contact point

Organisation

Menarini Ricerche S.p.A.

Contact name

Dr Monica Bertolotti

Public contact point

Organisation

Menarini Ricerche S.p.A.

Contact name

Dr Monica Bertolotti

Third parties 8

Locations

5 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 113 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications