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This study evaluated the safety, pharmacokinetics and efficacy of ceftobiprole in term and pre-term newborn babies and infants up to 3 months of age with late-onset sepsis (LOS). Ceftobiprole is an antibiotic which belongs to a group of medicines called 'cephalosporin antibiotics'. It is approved for its use to treat adults and children with pneumonia in many European and non-European countries.
This was a multicenter, open-label, single-arm, multiple-dose study of intravenous (IV) ceftobiprole medocaril (prodrug of the active moiety ceftobiprole). It could be combined with ampicillin and/or an aminoglycoside based on the Investigator's judgement according to manufacturer's instructions and/or local standard of care.
Following screening, ceftobiprole was administered as a 2-hour infusion at a dose of 7.5 mg/kg every 12 hours to 15 mg/kg every 8 hours, depending on age and weight.
The target treatment duration was 3-10 days, which could be extended to 14 days if considered clinically necessary by the Investigator.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Arm: Ceftobiprole | Experimental | Ceftobiprole medocaril: 7.5 mg/kg to 15 mg/kg |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ceftobiprole medocaril | Drug | Ceftobiprole medocaril: 7.5 mg/kg every 12 hours to 15 mg/kg every 8 hours, administered IV as a 2-hour infusion. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Patients With Adverse Events (AEs) | Number of patients with AEs, serious adverse events (SAEs), AEs leading to discontinuations and AEs of special interest | Up to 5-7 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum Observed Plasma Concentration (Cmax) of Ceftobiprole, Ceftobiprole Medocaril, and Open-ring Metabolite | Observed pharmacokinetic parameter Cmax of ceftobiprole (the active moiety), its pro-drug ceftobiprole medocaril and the open-ring metabolite in term and pre-term neonates with post-natal age up to 3 months | On treatment Day 3 prior to and 2, 4, and 8 hours after the start of the first ceftobiprole infusion of the day |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marc Engelhardt, MD | Basilea Pharmaceutica International Ltd, Allschwil | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| NorthShore University HealthSystem-Evanston Hospital | Evanston | Illinois | 60201 | United States | ||
| West Virginia University |
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A total of 11 patients were screened for enrollment in this study, two of whom failed the screening process. Nine patients (six pre-term neonates and three term neonates) were enrolled and assigned to the study treatment
Treatment was administered in hospital setting
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| ID | Title | Description |
|---|---|---|
| FG000 | Pre-term Neonates | Pediatric patients (gestational age ≥ 24 to 36 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. |
| FG001 | Term Neonates | Pediatric patients (gestational age ≥ 37 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pre-term Neonates | Pediatric patients (gestational age ≥ 24 to 36 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. Patients were treated with ceftobiprole 7.5 mg/kg or 10 mg/kg (bodyweight < 4 kg) infused over 2 hours and administered every 12 hours. Ceftobiprole may have been combined with locally-provided ampicillin and/or an aminoglycoside based on the Investigator's judgment. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Patients With Adverse Events (AEs) | Number of patients with AEs, serious adverse events (SAEs), AEs leading to discontinuations and AEs of special interest | The safety population consists of all enrolled patients who received at least one dose of ceftobiprole | Posted | Count of Participants | Participants | Up to 5-7 weeks |
|
Up to 5-7 weeks
Adverse event (AE) collection occurred after first study-drug administration, all AEs are considered to be "treatment emergent".
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pre-term Neonates | Pediatric patients (gestational age ≥ 24 to 36 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. Patients were treated with ceftobiprole 7.5 mg/kg or 10 mg/kg (bodyweight < 4 kg) infused over 2 hours and administered every 12 hours. Ceftobiprole may have been combined with locally-provided ampicillin and/or an aminoglycoside based on the Investigator's judgment. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thrombocytosis | Blood and lymphatic system disorders | MedDRA 25.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Marc Engelhardt, MD, Study Director | Basilea Pharmaceutica International Ltd, Allschwil | +41 79 701 0551 | marc.engelhardt@basilea.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 9, 2024 | Jun 12, 2025 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 26, 2025 | Jun 12, 2025 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000071074 | Neonatal Sepsis |
| ID | Term |
|---|---|
| D018805 | Sepsis |
| D007239 | Infections |
| D007232 | Infant, Newborn, Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
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| ID | Term |
|---|---|
| C505439 | ceftobiprole medocaril |
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| Number of Patients With a Clinical Response | Clinical cure rate at the end of treatment (EOT) at day 3-14 and test of cure (TOC) at 7-14 days after last ceftobiprole dose visits in the Intent-to-Treat (ITT) population | Up to 28 days |
| Number of Participants With Improved Signs and Symptoms of Late Onset Sepsis (LOS) | Improved signs and symptoms of LOS (including fever, hypothermia, abnormal heart rate, signs of impaired circulation, petechial rash or sclerema neonatorum, respiratory distress, gastrointestinal distress, irritability, lethargy and/or muscular or arterial hypotonia) assessed at Day 3, EOT, and TOC visits (ITT) populations. | Up to 28 days |
| Number of Patients With a Microbiological Response | Microbiological eradication or presumed eradication rate at the EOT and TOC visits. | Up to 28 days |
| Morgantown |
| West Virginia |
| 26506 |
| United States |
| MHAT Dr. Stamen Iliev AD Montana, Neonatology Department | Montana | 3400 | Bulgaria |
| UMHAT "Sveti Georgi" EAD, Pediatric surgery Clinic | Plovdiv | 4000 | Bulgaria |
| "Acibadem City Clinic University Hospital Tokuda" EAD, Neonatology Department | Sofia | 1407 | Bulgaria |
| Tallinn Childrens' Hospital | Tallinn | 13419 | Estonia |
| Klinikum der Universität München, Kinderklinik und Kinderpoliklinik im Dr. von Haunerschen Kinderspital | Munich | Bavaria | 80337 | Germany |
| Pauls Stradins Clinical University Hospital | Riga | 1002 | Latvia |
| Children Clinical University Hospital - Neonatology Clinic | Riga | 1004 | Latvia |
| Lithuanian Health Science University Hospital Kauno klinikos - Neonatology Clinic | Kaunas | 50161 | Lithuania |
| Vilnius University Hospital Santaros klinikos - Neonatology Center | Vilnius | 08410 | Lithuania |
| Ginekologiczno-Położniczy Szpital Kliniczny im. Marcinkowskiego | Poznan | 60-535 | Poland |
| Szpital Uniwersytecki - Klinika Neonatologii | Wroclaw | 50-556 | Poland |
| Univerzitna nemocnica Martin | Martin | 03659 | Slovakia |
| Cerebrospinal fluid test positive for S. aureus |
|
| BG001 | Term Neonates | Pediatric patients (gestational age ≥ 37 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. Patients were treated with ceftobiprole 10 mg/kg (bodyweight < 4 kg) or 15mg/kg (bodyweight ≥ 4 kg) infused over 2 hours and administered every 12 hours. Ceftobiprole may have been combined with locally-provided ampicillin and/or an aminoglycoside based on the Investigator's judgment |
| BG002 | Total | Total of all reporting groups |
| Days |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Gestational age | Mean | Standard Deviation | Weeks |
|
| Baseline weight | Mean | Standard Deviation | gram |
|
| Term Neonates |
Pediatric patients (gestational age ≥ 37 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. Patients were treated with ceftobiprole 10 mg/kg (bodyweight < 4 kg) or 15mg / kg (bodyweight ≥ 4 kg) infused over 2 hours and administered administered every 12 hours. Ceftobiprole may have been combined with locally-provided ampicillin and/or an aminoglycoside based on the Investigator's judgment. |
|
|
| Secondary | Maximum Observed Plasma Concentration (Cmax) of Ceftobiprole, Ceftobiprole Medocaril, and Open-ring Metabolite | Observed pharmacokinetic parameter Cmax of ceftobiprole (the active moiety), its pro-drug ceftobiprole medocaril and the open-ring metabolite in term and pre-term neonates with post-natal age up to 3 months | Pharmacokinetics (PK) population All patients who received at least one dose of ceftobiprole and had at least one sample of plasma concentration measurement obtained by the appropriate methodology. | Posted | Median | Full Range | μg/mL | On treatment Day 3 prior to and 2, 4, and 8 hours after the start of the first ceftobiprole infusion of the day |
|
|
|
| Secondary | Number of Patients With a Clinical Response | Clinical cure rate at the end of treatment (EOT) at day 3-14 and test of cure (TOC) at 7-14 days after last ceftobiprole dose visits in the Intent-to-Treat (ITT) population | The ITT population consists of all enrolled patients who received at least one dose of ceftobiprole. | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Number of Participants With Improved Signs and Symptoms of Late Onset Sepsis (LOS) | Improved signs and symptoms of LOS (including fever, hypothermia, abnormal heart rate, signs of impaired circulation, petechial rash or sclerema neonatorum, respiratory distress, gastrointestinal distress, irritability, lethargy and/or muscular or arterial hypotonia) assessed at Day 3, EOT, and TOC visits (ITT) populations. | The ITT population consists of all enrolled patients who received at least one dose of ceftobiprole. | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| Secondary | Number of Patients With a Microbiological Response | Microbiological eradication or presumed eradication rate at the EOT and TOC visits. | The microbiological Intent-to-treat (mITT) population consists of all patients in the ITT population with a causative pathogen identified at baseline. | Posted | Count of Participants | Participants | Up to 28 days |
|
|
|
| 0 |
| 6 |
| 1 |
| 6 |
| 3 |
| 6 |
| EG001 | Term Neonates | Pediatric patients (gestational age ≥ 37 weeks), with post-natal age ranging from ≥ 3 days to ≤ 3 months. Patients were treated with ceftobiprole 10 mg/kg (bodyweight < 4 kg) or 15mg / kg (bodyweight ≥ 4 kg) infused over 2 hours and administered administered every 12 hours. Ceftobiprole may have been combined with locally-provided ampicillin and/or an aminoglycoside based on the Investigator's judgment. | 0 | 3 | 1 | 3 | 3 | 3 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Enterobacter sepsis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Intraventricular haemorrhage neonatal | Nervous system disorders | MedDRA 25.1 | Systematic Assessment |
|
| Bronchopulmonary dysplasia | Respiratory, thoracic and mediastinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 25.1 | Systematic Assessment |
|
| Adrenal haemorrhage | Endocrine disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 25.1 | Systematic Assessment |
|
| Osteomyelitis | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Sepsis neonatal | Infections and infestations | MedDRA 25.1 | Systematic Assessment |
|
| Vena cava thrombosis | Vascular disorders | MedDRA 25.1 | Systematic Assessment |
|
| Oedema | General disorders | MedDRA 25.1 | Systematic Assessment |
|
| Withdrawal syndrome | General disorders | MedDRA 25.1 | Systematic Assessment |
|
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| D018746 | Systemic Inflammatory Response Syndrome |
| D007249 | Inflammation |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Open-ring metabolite |
|
| Unevaluable |
|
| TOC |
|
| Unchanged |
|
| Worsened |
|
| Not done |
|
| EOT |
|
| TOC |
|
| Persistence |
|
| Unevaluable |
|
| TOC |
|