E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Prevention of Staphylococcal Sepsis in Very Low Birth Weight (VLBW) Neonates |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040049 |
E.1.2 | Term | Sepsis neonatal |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056430 |
E.1.2 | Term | Staphylococcal sepsis |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objectives of the study are to confirm the safety of Pagibaximab Solution for Infusion in VLBW infants and to determine the efficacy of the drug in reducing the incidence of staphylococcal sepsis by study day 35 (in relation to placebo) in the modified intent-to-treat population (defined as all subjects who receive at least one dose of Pagibaximab Solution for Infusion or placebo). Staphylococcal sepsis will be diagnosed by new onset of two or more clinical signs of sepsis and either one positive peripheral blood culture (non-catheter) for S. aureus or two positive peripheral blood cultures for CoNS as defined in the protocol. |
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E.2.2 | Secondary objectives of the trial |
The first secondary objective is reduction in the initial secondary endpoint defined by: a combination of the primary endpoint plus staphylococcal infections that do not meet the primary endpoint but do meet the criteria of one normally sterile body fluid (non-blood) culture that is positive for the S. aureus or two normally sterile body fluid cultures that are positive for CoNS obtained within 24 hours of each other. One or both positive cultures for CoNS obtained from normally sterile body fluid cultures may be non-blood for this secondary objective. Additional secondary objectives include reduction in - staphylococcal sepsis in the subgroup of infants weighing 600-900 grams at birth; - sepsis caused by CoNS alone; - sepsis caused by S. aureus alone; - the number of subjects with sepsis caused by any organism; - the number of subjects with positive blood cultures due to organisms other than staphylococci; and - all-cause mortality. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. In-patient at a Neonatal Intensive Care Unit (NICU) 2. Informed consent obtained from the legally authorized representative(s) 3. Less than 48 hours after birth at the time of initiation of the first infusion (first infusion to be given as soon as possible after birth) 4. Birth weight from 600 grams to 1200 grams 5. Estimated gestation age ≤33 weeks as determined by the neonatologist 6. Existing intravenous access at the time of first infusion
For multiple gestations, twins or triplets may be enrolled for each subject that meets the entry criteria. These subjects will be individually randomized like other subjects in the study. |
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E.4 | Principal exclusion criteria |
1. Infants with proven staphylococcal sepsis as per this protocol prior to randomization 2. Infants with a concomitant infection or other medical condition, whose participation, in the opinion of the Investigator and/or medical advisor, may create an unacceptable additional risk 3. Currently receiving, recently received, or planned to receive other agents (e.g., investigational or IVIG) that could interfere with conduct, results or interpretation of this study 4. Severe congenital or chromosomal anomaly that would limit life expectancy or require corrective measures during the period of this study 5. Uncontrolled seizures |
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of staphylococcal sepsis between study days 0-35, as defined by: At least two clinical signs of sepsis, AND EITHER - One positive peripheral blood culture (non-catheter) for S. aureus, OR - Two positive peripheral blood cultures for CoNS obtained within 24 hours |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |