Clinical Trials Register

Summary
EudraCT Number:	2013-001998-24
Sponsor's Protocol Code Number:	ME3827/1-1
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2014-05-16
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - BfArM

A.2

EudraCT number

2013-001998-24

A.3

Full title of the trial

A prospective, multicenter, double blind, placebo-controlled, two-arm parallel group phase 3 trial to evaluate the effect of early postnatal additional high dose oral vitamin A supplementation of 5000 IU/kg/d versus placebo for 28 days for preventing bronchopulmonary dysplasia (BPD) or death in extremely-low-birth-weight (ELBW) infants.

A.3.1

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

Oral vitamin A supllementation versus placebo for preventing for 28 days for preventing bronchopulmonary dysplasia (BPD) or death in extremely-low-birth-weight (ELBW) infants.

A.3.2

Name or abbreviated title of the trial where available

NeoVitaA

A.4.1

Sponsor's protocol code number

ME3827/1-1

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Saarland University
B.1.3.4	Country	Germany
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	German Research Foundation
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Saarland University, Department of Pediatrics
B.5.2	Functional name of contact point	PD Dr. med. Sascha Meyer
B.5.3	Address:
B.5.3.1	Street Address	Campus Homburg, Building 9, FR 2.15
B.5.3.2	Town/ city	Homburg
B.5.3.3	Post code	66421
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4968411628313
B.5.5	Fax number	+4968411628310
B.5.6	E-mail	sascha.meyer@uks.eu

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	Vitadral® Tropfen
D.2.1.1.2	Name of the Marketing Authorisation holder	Aristo Pharma GmbH, Berlin
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Vitadral Tropfen
D.3.4	Pharmaceutical form	Oral solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Retinyl Palmitate
D.3.9.3	Other descriptive name	RETINOL PALMITATE
D.3.9.4	EV Substance Code	SUB04225MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30.2
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Oral solution
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Preventing bronchopulmonary dysplasia (BPD) or death in extremely-low-birth-weight (ELBW) infants.

Prävention der bronchopulmonalen Dysplasie (BPD) oder Tod bei extrem Frühgeborenen.

E.1.1.1

Medical condition in easily understood language

Prevention of severe and often chronic lung disease or death of preterm infants.

Verhinderung schwerer und häufig chronisch verlaufender Lungenerkrankung oder Tod von Frühgeborenen.

E.1.1.2

Therapeutic area

Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

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 investigate whether early postnatal additional high dose oral vitamin A supplementation (5000 IU/kg body weight/day) for 28 days reduces the absolute risk of bronchopulmonary dysplasia (moderate/severe) or death at 36+0 weeks PMA or at date of discharge to home, whichever comes first in ELBW infants when compared to placebo treatment.

Die primäre Zielsetzung der Studie ist die Untersuchung, ob die frühzeitige zusätzliche orale Hochdosis Vitamin A Therapie (5000 IU/kg/Tag) für 28 Tage im Vergleich zu Placebo bei extrem Frühgeborenen das absolute Risiko der Bronchopulmonalen Dysplasie (moderate/schwere Verlaufsform) oder des Todes zum Zeitpunkt der 36+0 postmenstruellen Woche oder der Entlassung nach Hause, je nachdem welcher Zeitpunkt früher eintritt, reduziert.

E.2.2

Secondary objectives of the trial

To assess the impact on high dose oral vitamin A supplementation on:
1. All-cause mortality
2. All grade BPD (mild/moderate/severe)
3. Duration of PPV and PPS
4. Duration of evolving BPD since birth
5. Serum VA status
6. Retinopathy of prematurity (ROP)
7. Intraventricular hemorrhage (IVH)
8. Periventricular leukomalacia (PVL)
9. Necrotizing enterocolitis (NEC)
10. Safety and tolerability of study medication

Die sekundären Zielsetzungen der Studie sind die Untersuchung des Einflusses einer zusätzlichen oralen Hochdosis Vitamin A Therapie auf:
1. Sterblichkeit, alle Ursachen
2. BPD, alle Schweregrade
3. Zeitdauer von PPV (Positive Pressure Ventilation – positive Druck Beatmung) und PPS (Positive Pressure
Support – positive Druck Atemhilfe)
4. Zeitdauer der BPD Symptome seit Geburt
5. Serum Vitamin A Status
6. Frühgeborenen- Retinopathie (ROP)
7. Intraventrikuläre Blutung (IVH)
8. Periventrikuläre Leukomalazie (PVL)
9. Nekrotisierende Enterokolitis (NEK)
10. Sicherheit und Verträglichkeit der Studienmedikation
11. Pulmonary assessment at 12 and 24 months corrected gestational age
12. Neurological assessment at 24 months corrected gestational age
13. Anthropometric data

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Neonates with a birth weight <1000 g.
Neonates with a gestational age < 32+0 weeks at time of inclusion into the Trial.
Who receive any oxygen supplementation or respiratory support after admission to the NICU
within 72 hours following birth.
Who (will) receive a basic VA supplementation of 1000 IU/kg body weight/day (7000 IU/kg
body weight/week).
Postnatal age <72 hours of life.
Minimal/enteral feeds (>2.5 / <10 ml/kg body weight per day) commenced.
Signed and dated informed parental or legal representative’s consent.

E.4

Principal exclusion criteria

≥1 major congenital abnormalities.
Congenital nonbacterial infection with overt signs at birth.
Terminal illness as evidenced by pH <7.0 for >2 hours or persistent bradycardia (heart rate
<100 bpm) associated with hypoxia for >2 hours.
Birth weight <400 g.
Participation in another clinical trial according to German Drug Law (AMG).

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint of the study is the combined incidence of BPD (moderate/severe) or death at 36+0 weeks PMA or at date of discharge to home, whichever comes first.

E.5.1.1

Timepoint(s) of evaluation of this end point

36+0 weeks

E.5.2

Secondary end point(s)

1. Any death
2. Any occurrence of BPD (mild/moderate/severe)
3. Days of PPV or PPS
4. Days of evolving BPD
5. Serum retinol levels, RBP, RE
6. Diagnosis of ROP using ophthalmological examination
7. Diagnosis of all grades of IVH using cranial ultrasound investigation
8. Diagnosis of PVL using cranial ultrasound investigation
9. Diagnosis of NEC using clinical examination and X-ray investigation
10. Occurrence of any adverse event
11. Total number of antibiotic treatments at 12 and 24 months of c.a.
12. Total number of antibiotic treatments for pulmonary infections at 12 and 24 months of c.a.
13. Total number of hospital admissions at 12 and 24 months of c.a.
14. Total number of hospital admissions for pulmonary infections at 12 and 24 months of c.a.
15. Results of Bayley-II or Bayley III scale at 24 months of c.a.
16. Anthropometric data at 12 and 24 months of c.a.
17. Neurological and non-neurological diseases during the first 12 and 24 months c.a.
18. Use of supportive therapies and specific drug Treatment

E.5.2.1

Timepoint(s) of evaluation of this end point

36+0 weeks
12 months corrected age
24 months corrected age

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

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)

E.8.2.2

Placebo

Yes

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

last visit last subject

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

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:

1000

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:

1000

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

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

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

extremely low birth weight infants

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

914

F.4.2

For a multinational trial

F.4.2.1

In the EEA

914

F.4.2.2

In the whole clinical trial

914

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)

Subsequent treatment will be according to the individual needs of each patient.

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

2014-07-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-10-09

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials