Clinical Trials Register

Summary
EudraCT Number:	2011-001515-31
Sponsor's Protocol Code Number:	1
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-12-07
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Greece - EOF

A.2

EudraCT number

2011-001515-31

A.3

Full title of the trial

EFFICACY, PHARMACOKINETICS AND SAFETY OF MEROPENEM IN
INFANTS BELOW 90 DAYS OF AGE (INCLUSIVE) WITH CLINICAL OR
CONFIRMED LATE-ONSET SEPSIS: A EUROPEAN MULTICENTER
RANDOMISED PHASE III TRIAL

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Meropenem for the treatment of serious bacterial infections in neonates
and young infants

A.3.2

Name or abbreviated title of the trial where available

meropenem for the treatment of late onset neonatal sepsis

A.4.1

Sponsor's protocol code number

A.5.4

Other Identifiers

Name:

NEOMERO

Number:

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/26/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PENTA Foundation Onlus
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	European Commission
B.4.2	Country	European Union
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	PENTA Foundation Onlus
B.5.2	Functional name of contact point	c/o Dipartmento di Pediatria
B.5.3	Address:
B.5.3.1	Street Address	Via Giustiniani 3
B.5.3.2	Town/ city	Padova
B.5.3.3	Post code	35128
B.5.3.4	Country	Italy
B.5.4	Telephone number	393470957171
B.5.5	Fax number	390498753865
B.5.6	E-mail	management@neomero.org

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	MERREM*EV FL IG+F 20ML
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MEROPENEM
D.3.9.1	CAS number	96036-03-2
D.3.9.4	EV Substance Code	SUB08778MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	cefotaxime
D.3.2	Product code	cefotaxime
D.3.4	Pharmaceutical form	Powder for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous bolus use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CEFOTAXIME
D.3.9.1	CAS number	63527-52-6
D.3.9.4	EV Substance Code	SUB07405MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	500 to 1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	gentamicin
D.3.2	Product code	gentamicin
D.3.4	Pharmaceutical form	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent) Intravenous bolus use (Noncurrent) Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GENTAMICIN
D.3.9.1	CAS number	1403-66-3
D.3.9.4	EV Substance Code	SUB02326MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

suspected or proven late onset neonatal sepsis

E.1.1.1

Medical condition in easily understood language

sepsis in neonates and young infants

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	SOC
E.1.2	Classification code	10021881
E.1.2	Term	Infections and infestations
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To compare the efficacy at TOC visit of meropenem to the standard of
care in the treatment of clinical or confirmed LOS in infants ≤ 90 days of
postnatal age.

E.2.2

Secondary objectives of the trial

- To compare the safety profile of meropenem to SOC.
- To compare the efficacy of meropenem to SOC in confirmed sepsis.
- To compare the response to meropenem and SOC.
- To compare the efficacy at TOC visit of meropenem to SOC by SOC
regimen.
- To compare survival at Day 28 in the meropenem and SOC arms.
- To evaluate new infections and relapses.
- To define the organisms causing LOS.
- To study antibacterial susceptibility of LOS-causing organisms and to
describe clinical and
microbiological responses according to this.
- To compare gut colonization by resistant organisms.
- To compare bacterial eradication by treatment arm.
- To compare time to NICU discharge.
- To describe PK of meropenem in infants ≤ 90 days of postnatal age
with LOS.
- To evaluate genetic parameters that may affect response to therapy.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Pharmacokinetics of meropenem in neonates infants ≤ 90 days of
postnatal age with LOS. 11.05.2011/ version 1.0
Microbiology substudy. 11.05.2011/ version 1.0
Genetic determinants of susceptibility to sepsis and to differential
responses to Meropenem. 11.05.2011/ version 1.0

E.3

Principal inclusion criteria

- Informed consent form signed by the parents/carers
- Chronological age below 90 days inclusive
- Chronological age greater or equal to 72 hours of life at beginning of
LOS
- Clinical or confirmed sepsis

E.4

Principal exclusion criteria

- Administration of any systemic antibiotic regimen for more than 24
hours prior to the administration of the study drug, unless the change is
driven by the lack of efficacy of the former regimen;
- Severe congenital malformations if the infant is not expected to
survive for more than 3 months;
- Other situations where the treating physician considers a different
antibiotic regimen necessary;
- Known intolerance or contraindication to study medication;
- Participation in any other clinical study of investigational drugs;
- Renal failure (as defined by Akcan-Arikan et al., 2007) and
requirement for haemofiltration or peritoneal dialysis;
- Confirmed sepsis with microorganisms known to be resistant to study
therapies.

E.5 End points

E.5.1

Primary end point(s)

Favourable outcome at the TOC visit performed 2 days after COT, defined
as an infant alive, with resolution or significant improvement of all
abnormalities that defined LOS, with microbiological eradication and no
change in the treatment allocated at randomisation.

E.5.1.1

Timepoint(s) of evaluation of this end point

TOC visit is performed 2 days after COT (completion of 11 +/- 3 days of
allocated antibiotic therapy)

E.5.2

Secondary end point(s)

- Description of all clinical and biological adverse events experienced by
infants receiving meropenem or comparator agents.
- Clinical and biological response in all patients and also in patients with
positive baseline cultures at Day 3, at COT, at EOT and EOAT.
- Survival at Day 28.
- New infections or relapses of LOS that occur between TOC and FU visit
in participants with a favourable outcome at TOC visit.

E.5.2.1

Timepoint(s) of evaluation of this end point

End of allocated treatment (EOAT) -- the point in time when allocated
therapy for LOS is stopped, that means the last day of allocated
treatment. If EOAT is within 11 ± 3 days and no other antibiotic is
continued, EOAT = COAT
End of treatment (EOT) signifies the point in time when antibiotic
therapy for LOS is stopped. If EOT is within 11 ± 3 days, EOT = COT. If
there is no change of allocated therapy COT = COAT.
FU (follow up) visit is performed at Day 28 ± 3.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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

IDMC performs an interim review of the trial's progress including
updated figures on recruitment, data quality, and main safety and
efficacy outcomes. Based on its review,
the IDMC will provide within 15 days after each of its meetings a brief
formal written report with recommendations to the sponsor regarding
study modification, continuation or termination.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

550

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

Yes

F.1.1.2.1

Number of subjects for this age range:

200

F.1.1.3

Newborns (0-27 days)

Yes

F.1.1.3.1

Number of subjects for this age range:

200

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

150

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

neonates aged 72 hours to 90 days (inclusive)

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

550

F.4.2.2

In the whole clinical trial

550

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

NONE

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-01-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-12-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-12-17

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