Clinical Trials Register

Summary
EudraCT Number:	2009-013884-21
Sponsor's Protocol Code Number:	GLPG0303-CL-204
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2009-09-09
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

Germany - BfArM

A.2

EudraCT number

2009-013884-21

A.3

Full title of the trial

A randomized, international, multi centre study to assess the efficacy and safety of intravenous PEG-liposomal prednisolone sodium phosphate (Nanocort®) vs intravenous methylprednisolone (Solu-Medrol®) treatment in patients with acute exacerbation of relapsing-remitting Multiple Sclerosis or in patients with clinically isolated syndrome (CIS)

A.3.1

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

A.4.1

Sponsor's protocol code number

GLPG0303-CL-204

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01039103

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	Enceladus Pharmaceuticals BV
B.1.3.4	Country	Netherlands
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Enceladus Pharmaceuticals BV
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Enceladus Pharmaceuticals BV
B.5.2	Functional name of contact point	Enceladus Pharmaceuticals BV
B.5.3	Address:
B.5.3.1	Street Address	Science Park 406
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1098XH
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	+31207512051
B.5.5	Fax number	---
B.5.6	E-mail	bart@enceladus.nl

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	No
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	PEG-liposomal Prednisolone Sodium Phosphate
D.3.2	Product code	Nanocort
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
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	Prednisolone Sodium Phosphate
D.3.9.1	CAS number	125-02-0
D.3.9.3	Other descriptive name	PREDNISOLONE SODIUM PHOSPHATE
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.0 to 3.2
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	Yes
D.3.11.13.1	Other medicinal product type	liposomal encapsulated active substance (Prednisolone Sodium Phosphate)
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.2.1.1.1	Trade name	Solu-Medrol
D.2.1.1.2	Name of the Marketing Authorisation holder	Pfizer bv
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	METHYLPREDNISOLONE SODIUM SUCCINATE
D.3.9.1	CAS number	03/03/2375
D.3.9.3	Other descriptive name	METHYLPREDNISOLONE SODIUM SUCCINATE
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	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.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

Patients with acute exacerbation of Relapsing-Remitting Multiple Sclerosis or Clinically Isolated Syndrome

E.1.1.1

Medical condition in easily understood language

Relapsing-Remitting Multiple Sclerosis or Clinically Isolated Syndrome

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.0
E.1.2	Level	PT
E.1.2	Classification code	10028245
E.1.2	Term	Multiple sclerosis
E.1.2	System Organ Class	10029205 - Nervous system disorders

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 assess the efficacy and safety of intravenous Polyethylene glycosylated (PEG)-liposomal prednisolone sodium phosphate (Nanocort) vs intravenous methylprednisolone treatment in patients with acute exacerbation of relapsing-remitting Multiple Sclerosis (RRMS) or in patients with CIS.

E.2.2

Secondary objectives of the trial

To explore the levels of free prednisolone and prednisolone phosphate

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients who are eligible for inclusion will be female or male patients, 18 to 65 years of age (inclusive), who have a diagnosis of RRMS (per McDonald criteria, 2005) with dissemination in time and space or a diagnosis of CIS confirmed by MRI. Patients with CIS who only have optic neuritis will be excluded from this study, a maximum Expanded Disability Status Scale (EDSS) score of ≤ 6.0, who have new neurological symptoms or exacerbation of prior neurological symptoms of over 24 hours duration but <7 days duration, verified by neurological examination and who have signed an informed consent.

E.4

Principal exclusion criteria

Patients will be excluded from participation in the study who have
-Primary progressive MS.
-Secondary progressive MS without superimposed relapses.
-Received systemic corticosteroids within 4 weeks of screening for treatment of MS or other conditions. If non-systemic steroids (topical, inhalation, ocular) are being used for other chronic inflammatory conditions, patients may be included at the discretion of the investigator after discussion with the medical monitor.
-Known contraindications or hypersensitivity to parenteral steroids e.g. systemic infection such as mycoses or parasitoses, acute viral infections (herpes zoster, herpes simplex, varicella), hepatitis B surface antigen (HBsAg) positive chronic active hepatitis, immunisations within recent weeks, lymphadenitis after Bacille Calmette-Guérin (BCG) vaccination, history of psychiatric problems including prior steroid psychosis, gastroduodenal or -intestinal ulcer, uncontrolled hypertension, severe osteoporosis and narrow- and wide-angle glaucoma
-Previous treatment with azathioprine, mitoxantrone, natalizumab, intravenous immunoglobulin or plasmapheresis in the last 6 months.
-Women who are lactating, pregnant (positive pregnancy test at Screening), or planning to become pregnant during the course of the study.
-Unwillingness to use reliable and acceptable contraceptive methods (e.g. implants, injectables, combined oral contraceptives, intrauterine devices [IUDs], sexual abstinence or vasectomised partner) throughout the study and till 3 months after last study medication administration except for female patients who are surgically sterile (post hysterectomy or at least 1 year post tubal ligation) or at least 2 years postmenopausal.
-Any concurrent illness, disability or clinically significant abnormality that may affect the interpretation of clinical efficacy or safety data or prevent the subject from safely completing the assessments required by the protocol.
- History of malignancy within the last 5 years with exception of basal cell skin carcinoma
- Chronic diseases of the immune system, malignancies, acute pulmonary disease, cardiac failure, severe depression etc. or unstable medical conditions.
-Cardiac pacemaker or any other type of metal implant or with any other contraindication for MRI (including known allergy to gadolinium).
-Participation in another clinical study within 60 days of screening.
- Recent history or suspicion of current drug abuse (including analgesic abuse) or alcohol abuse within the last 6 months prior to Screening.
- Medical, psychiatric, cognitive, or other conditions that compromise the patient's ability to understand the patient information, to give informed consent, to comply with the trial protocol, or to complete the study.
- Known history of diabetes mellitus.
- History of any other than MS autoimmune conditions or immunodeficiency syndromes.

E.5 End points

E.5.1

Primary end point(s)

Change in gadolinium-enhanced T1-weighted lesions according to the McDonald criteria (2005) from Day 8 to Week 8.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 8

E.5.2

Secondary end point(s)

Change in gadolinium-enhanced T1-weighted lesions according to the McDonald criteria (2005) from Day 8 to Week 4.

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 4

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

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

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

Yes

E.8.1.7.1

Other trial design description

assessor-blinded, i.e. those who evaluate the study outcome are not informed the treatment

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

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 of the last subject undergoing the trial

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

F.1.1.1

In Utero

F.1.1.2

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

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)

Yes

F.1.2.1

Number of subjects for this age range:

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

Yes

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

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

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)

normal treatment of that condition

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

2009-11-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-10-15

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2011-11-21

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