Clinical Trials Register

Summary
EudraCT Number:	2011-001521-25
Sponsor's Protocol Code Number:	2011-001521-25
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

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

2011-001521-25

A.3

Full title of the trial

Pharmacokinetics and safety of meropenem in infants below 90 days of
age (inclusive) with probable and confirmed meningitis: a European
multicentre phase I-II trial

A.3.1

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

Pharmacokinetics and safety of meropenem in infants below 90 days of
age (inclusive) with probable and confirmed meningitis: a European
multicentre phase I-II trial

A.4.1

Sponsor's protocol code number

2011-001521-25

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/001/2010

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	PENTA Foundation (Fondazione Penta 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	Fondazione PENTA Onlus
B.5.2	Functional name of contact point	Fondazione PENTA Onlus
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	3904982113585
B.5.5	Fax number	390498753865
B.5.6	E-mail	carlog@pediatria.unipd.it

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 1g+F 20 ml
D.2.1.1.2	Name of the Marketing Authorisation holder	ASTRAZENECA SpA
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 infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
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

proven or suspected bacterial meningitis in neonates and infants up to
90 days of age

E.1.1.1

Medical condition in easily understood language

meningitis in neonates and infants

E.1.1.2

Therapeutic area

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

MedDRA Classification

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 study the pharmacokinetics (plasma and cerebrospinal fluid) of
meropenem in infants ≤ 90 days of postnatal age with probable or
confirmed bacterial meningitis and to characterize the safety profile of
meropenem in the treatment of infants ≤ 90 days of postnatal age with
probable or confirmed bacterial meningitis.

E.2.2

Secondary objectives of the trial

- To describe the efficacy of meropenem on day 3, at end of allocated
treatment (EOAT), at test of cure (TOC) and at follow up (FU).
- To evaluate survival at FU
- To evaluate further episodes of meningitis (relapse or new infection)
occurring between TOC and FU visits
- To define the organisms causing neonatal meningitis
- To describe the antibacterial susceptibility of meningitis-causing
organisms and to describe the clinical and microbiological response
according to this
- To evaluate mucosal colonization by resistant organisms before and
after treatment with meropenem
- To evaluate bacterial eradication
- To evaluate functional 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

Genetic determinants of susceptibility to meningitis and to differential responses to Meropenem 16.05.2011/ version 1.0

E.3

Principal inclusion criteria

- Informed consent form signed by the parents/carers
- Chronological age below 90 days inclusive
- The presence of: clinical signs consistent with bacterial meningitis
(clinical signs of meningitis are: fever or hypothermia or temperature
instability PLUS 1 or more neurological findings e.g. coma, seizures, neck
stiffness, apnoea, bulging fontanelle) OR CSF pleocytosis (≥ 20 cells /
mm3 OR a positive Gram stain of CSF.

E.4

Principal exclusion criteria

- Presence of a CSF device
- Proven viral or fungal meningitis
- Severe congenital malformations if the infant is not to expect to
survive for more than 3 months
- Other situations where the treating physician considers a different
empiric antibiotic regimen necessary
- Known intolerance or contraindication to the study medication
- Participation in any other clinical study of an investigational medicinal
product
- Renal failure and requirement of haemofiltration or peritoneal dialysis
- Meningitis with an organism known to be resistant to meropenem

E.5 End points

E.5.1

Primary end point(s)

- The PK of meropenem (plasma and CSF) in infants ≤ 90 days of age
diagnosed with probable and confirmed BM
- Adverse events experienced by infants receiving meropenem.

E.5.1.1

Timepoint(s) of evaluation of this end point

Meropenem PK will be studied in steady state on the 3rd study day.
Clinical and biological adverse events will be recorded until follow-up
visit on Day 45 +/- 3

E.5.2

Secondary end point(s)

- A favourable outcome defined at Test of Cure visit (TOC), 2 days after
EOAT as an infant fulfilling the following criteria: Alive with clinical and
bacteriological resolution of the abnormalities that defined BM at entry
and no occurrence of any new clinical or laboratory abnormalities
requiring a new course of antibiotic therapy and no modification of the
initial meropenem therapy (for more than 24 hours).
- Clinical, biological and microbiological response at day 3, at EOAT, at
TOC and at FU;
- Survival at FU visit;
- Auditory function as assessed by brain-stem auditory evoked
potentials between COT and FU visits;
- Neurological evaluation as assessed by cerebral ultrasound (and if
persistently abnormal, by MRI or CT) at any time up until the FU visit;
- The organisms causing neonatal meningitis;
- The antibiotic susceptibility of bacteria causing BM;
- Mucosal colonisation with antibiotic resistant bacteria or fungi at
enrolment, EOAT and FU / discharge (whichever is earlier)
- Genetic parameters that can affect response to therapy

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 meningitis is stopped, that means the last day of allocated
treatment.
TOC visit is performed 2 ± 1 days after EOAT
Follow up (FU) visit is performed at Day 45 ± 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

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

All infants will be treated with meropenem

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

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 outcomes. Based on its review, the IDMC will provide within 15 days after each of its meetings a 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:

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:

F.1.1.3

Newborns (0-27 days)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

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

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

neonates and infants aged up to 90 days

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

G. Investigator Networks to be involved in the Trial

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	2014-12-10

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