Clinical Trials Register

Summary
EudraCT Number:	2012-000674-31
Sponsor's Protocol Code Number:	CFTY720DDE15TS
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-04-27
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

Germany - BfArM

A.2

EudraCT number

2012-000674-31

A.3

Full title of the trial

A 3-year, multi-center study to describe the long term changes of optical coherence tomography (OCT) parameters in patients under treatment with Gilenya®

A.3.1

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

A 3-year, multi-center study to describe the long term changes of optical coherence tomography (OCT) parameters in patients under treatment with Gilenya®

A.4.1

Sponsor's protocol code number

CFTY720DDE15TS

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	Novartis Pharma GmbH
B.1.3.4	Country	Germany
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	Novartis Pharma GmbH
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	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Project Leader
B.5.3	Address:
B.5.3.1	Street Address	Roonstr. 25
B.5.3.2	Town/ city	Nürnberg
B.5.3.3	Post code	90429
B.5.3.4	Country	Germany
B.5.4	Telephone number	004991127313187
B.5.5	Fax number	004991127317187
B.5.6	E-mail	francisca.blumhagen@novartis.com

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	Gilenya
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Ltd
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.3.1	Product name	Fingolimod
D.3.2	Product code	FTY720
D.3.4	Pharmaceutical form	Capsule, hard
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.3.9.1	CAS number	162359-56-0
D.3.9.2	Current sponsor code	FTY720
D.3.9.3	Other descriptive name	Fingolimod Hydrochloride
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	0.5
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

RNFLT in Patients with relapsing remitting Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

Multiple Sclerosis

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	18.0
E.1.2	Level	PT
E.1.2	Classification code	10063399
E.1.2	Term	Relapsing-remitting 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 evaluate the change in average RNFL thickness (RNFLT) in RRMS patients treated with fingolimod over 36 months as assessed by OCT.

E.2.2

Secondary objectives of the trial

To evaluate the change in average RNFLT under fingolimod therapy from baseline to months 12 and 24 as assessed by OCT.
To evaluate change in quadrant RNFLT under fingolimod therapy from baseline to months 12, 24 and 36
To evaluate changes in total macular volume (TMV) under fingolimod therapy from baseline to months 12, 24 and 36.
To evaluate changes in ganglion cell layer thickness (GCLT) under fingolimod therapy from baseline to months 12, 24 and 36.
To compare changes in OCT parameters between eyes with and without history of optic neuritis and between right and left eye.
To evaluate safety and tolerability of fingolimod in MS patients followed for up to 36 months and specifically to determine the frequency of macular edema under treatment with oral fingolimod in this patient population.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent must be obtained before any assessment is performed.
2. Male or female subjects aged 18-65 years.
3. Subjects with relapsing remitting MS defined by 2010 revised McDonald criteria (see Appendix 4).
4. Patients with Expanded Disability Status Scale (EDSS) score of 0-6.0 inclusive (see Appendix 6).
5. Patients stable on immunomodulatory treatment with fingolimod for at least 1 month* and at most 4 months* prior to screening according to local label
6. Neurologically stable with no evidence of relapse within 30 days prior to inclusion date (visit 2)
7. Sufficient ability to read, write, communicate and understand

* one month is defined as 28 days

E.4

Principal exclusion criteria

1. Patients who have been treated with:
• systemic corticosteroids or immunoglobulins within 1 month* prior to screening;
• immunosuppressive medications such as azathioprine, cyclophosphamide, or methotrexate within 3 months* prior to screening;
• monoclonal antibodies (including natalizumab) within 3 months* prior to screening;
• mitoxantrone within 6 months* prior to screening
• cladribine at any time.
2. Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
3. Patients with any of the following cardiovascular conditions :
• history of myocardial infarction or with current unstable ischemic heart disease;
• Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the
Investigator (see Appendix 5);
• history or presence of a second-degree AV block, Type II or a third-degree AV
block
• patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or
III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide,
dofelitide);
• proven history of sick sinus syndrome;
• uncontrolled hypertension
4. Patients with severe respiratory disease, pulmonary fibrosis, or chronic obstructive
pulmonary disease (Class III-IV).
5. Patients with history of specific MRI findings (tumor, subdural haematoma, post-contusional changes, territorial stroke, neurodegenerative disorders, aneurysm/arteriovenous malformation, evidence of past macroscopic haemorrhage, or other relevant MRI findings that would interfere with evaluation)
6. Any severe disability or clinical impairment that can prevent the patient to meet all study requirements at the investigator`s discretion
7. History of malignancy of any organ system, treated or untreated, within the past 5 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
8. Patients who have received an investigational drug (excluding fingolimod) or therapy within 90 days or 5 half-lives of screening, whichever is longer.
9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hCG test (serum)
10. Patients with any ophthalmologic reason for RNFL pathology other than MS, such as: optic neuropathy, active advanced glaucoma, injury of the optic nerve based on the ophthalmologist’s clinical judgment
11. history or presence of severe myopia
a. in patients who have not had refractive surgery, a refractive error of greater than 6.00 diopters
b. pathologic fundus changes of high myopia, such as retinal pigmentary atrophy, besides peripapillary atrophy (atrophy involving the macula) or a staphyloma
c. in patients that have had previous refractive surgery, an axial eye length of greater than 26 mm
12. Acute optic neuritis within the past 6 months before screening
13. Evidence of advanced, non-proliferative or proliferative diabetic retinopathy
14. Presence of retinal conditions associated with edema, subretinal fluid, cysts, etc.
15. Concomitant use of drugs that may directly affect retinal structure and function (e.g.
chronic systemic corticosteroids [>30 consecutive days; doses higher than Cushing
threshold e.g. prednisone 7.5mg/d], intraocular anti-angiogenic drugs [ranibizumab, bevacizumab], intraocular steroids etc.)

* one month is defined as 28 days

E.5 End points

E.5.1

Primary end point(s)

To evaluate the change in average RNFL thickness (RNFLT) in RRMS patients treated with fingolimod over 36 months as assessed by OCT.

E.5.1.1

Timepoint(s) of evaluation of this end point

after 3 years

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

every year

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

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

Germany

Switzerland

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

LVLS

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:

100

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

100

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

100

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)

The investigator decides about further treament after the end of the study in the best interest of the patient. Gilenya is commercially available.

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

2012-05-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-01

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-02-18

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