Clinical Trials Register

Summary
EudraCT Number:	2010-022066-28
Sponsor's Protocol Code Number:	CFTY720DDE01
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:	2010-09-29
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

2010-022066-28

A.3

Full title of the trial

A 6-month multicenter, single-arm, open-label study to investigate changes in biomarkers after initiation of treatment with 0.5 mg fingolimod (FTY720) in patients with relapsing-remitting multiple sclerosis

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

CFTY720DDE01

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
B.5.2	Functional name of contact point

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 Limited
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	Gilenya
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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
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

relapsing remitting Multiple Sclerosis

E.1.1.1

Medical condition in easily understood language

relapsing remitting 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	14.1
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

The primary endpoints are the reduction of CD4+ and CD8+ naïve T cells (CCR7+CD45RA+), central memory T cells (CCR7+CD45RA-), central memory Th17 cells (CD4+ CCR4+ and CCR6+), and an elevation of effector memory T cells (CCR7- CD45RA-) in peripheral venous blood at month 6 versus baseline.

E.2.2

Secondary objectives of the trial

To investigate changes from baseline in B Lymphocytes, monocytes and NK cells after treatment start and during infection periods. This will be assessed by studying surface markers by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells (CD56).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent from patients capable of giving or withholding full informed
consent must be obtained before any assessment is performed.
2. Male or female subjects aged 18-65 years.
3.Subjects with relapsing remitting forms of MS defined by 2010 revised McDonald
criteria (see Appendix 4).
4.Patients with high disease activity despite treatment with a disease modifying therapy
(≥ 1 relapse in the previous year, ≥ 9 hyperintense T2 lesions or ≥1 Gd-enhancing
lesion or “non-responding” which could be defined as unchanged or increased relapse
rate or ongoing severe relapses compared to previous year)
or patients with rapidly evolving severe RRMS (e.g. ≥ 2 relapses with disease
progression in one year and ≥ 1 Gd-enhancing lesion or with a significant increase in
T2 lesions compared to a recent MRI).
5.Patients with Expanded Disability Status Scale (EDSS) score of 0-6.5 (see Appendix
8).
6.Sufficient ability to read, write, communicate and understand

E.4

Principal exclusion criteria

1. Patients with a manifestation of MS other than relapsing remitting MS.
2. Patients with a history of chronic disease of the immune system other than MS, which requires systemic immunosuppressive treatment, or a known immunodeficiency syndrome.
3. History or presence of malignancy (other than localized basal cell carcinoma of the skin and carcinoma in situ of the cervix) in the last 5 years
4. Diabetic patients with moderate or severe non-proliferative diabetic retinopathy or proliferative diabetic retinopathy and uncontrolled diabetic patients with HbA1c > 7%.
5. Diagnosis of macular edema during Screening Phase (patients with a history of macular edema will be allowed to enter the study provided that they do not have macular edema at the ophthalmic screening visit).
6. Patients with active systemic bacterial, viral or fungal infections, or known to have AIDS, Hepatitis B, Hepatitis C infection or to have positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests.
7. Negative for varicella-zoster virus IgG antibodies at Screening.
8. Have received any live or live attenuated vaccines (including for varicella-zoster virus or measles) within 1 month prior to baseline.
9. Patients who have received total lymphoid irradiation or bone marrow transplantation.
10. Patients who expect to be treated with any disease modifying drugs (DMD) during the study (i.e. IFN-β, glatiramer acetate); however no washout is needed for DMDs prior to baseline.
11. Patients who have been treated with:
•systemically applied corticosteroids or adrenocorticotropic hormones (ACTH) within 1 month prior to baseline;
•immunosuppressive medications such as azathioprine or methotrexate within 3 months prior to baseline;
•immunoglobulins and/or monoclonal antibodies (including natalizumab) within 3 months prior to baseline;
•cladribine at any time
•Cyclophosphamide and mitoxantrone within 6 months prior to start of fingolimod
12. Patients with any medically unstable condition, as assessed by the primary treating physician at each site.
13. Patients with any of the following cardiovascular conditions:
• Patients receiving antiarrythmics class Ia (e.g. quinidine, disopyramide, chinidin,
ajmaline, procainamide) or class III (e.g. amiodarone, bretylium, sotalol, ibutilide,
azimilide, dofetilide) or beta blockers
• Patients receiving heart rate lowering calcium channel blockers (e.g. verapamil,
diltiazem or ivabradine) or other substances which may decrease heart rate (e.g.
digoxin, anticholinesteratic agents or pilocarpine).
•Significant QT prolongation (QTc>470 msec (female) or >450 msec (males))
•cardiac failure at time of Screening (Class III, according to New York Heart Association Classification) or any severe cardiac disease as determined by the investigator;
•history of second degree AV block, sick-sinus syndrome or sinoatrial block.
• History of symptomatic bradycardia or recurrent syncope, known ischaemic heart
disease, cerebrovascular disease, history of myocardial infarction, congestive heart
failure, history of cardiac arrest, uncontrolled hypertension, or severe sleep apnea
•resting pulse rate <45 bpm;
14. Patients with any of the following pulmonary conditions:
•pulmonary fibrosis
•active tuberculosis
15. Patients with severe hepatic dysfunction (Child-Pugh-Class C)
16. Patients with any of the abnormal laboratory values:
•white blood cell (WBC) count <3,500/mm3 or lymphocyte count <800/mm3
17. Patients with any of the following neurologic/psychiatric disorders:
• history of substance abuse (drug or alcohol) in the past five years or any other factor (i.e.serious psychiatric condition) that may interfere with the subject’s ability to cooperate and comply with the study procedures;
•progressive neurological disorder, other than MS, which may affect participation in the study
18. Participation in any clinical research study evaluating another investigational drug or therapy within 6 months prior to baseline
19. 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 laboratory test (> 5mIU/ml)
20. Women of child-bearing potential defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS they are using two birth control methods, at least 1 of which must be a primary form.
21. History of hypersensitivity to the active substance or to any other of the excipients of the study drug.
22. Prior enrolment in a trial with fingolimod. Patients who failed to be enrolled in another clinical trial with fingolimod, i.e. screening failures, may be enrolled.

E.5 End points

E.5.1

Primary end point(s)

E.5.1.1

Timepoint(s) of evaluation of this end point

month 6

E.5.2

Secondary end point(s)

To investigate changes from baseline in B Lymphocytes, monocytes and NK cells after
treatment start and during infection periods. This will be assessed by studying surface markers
by FACS analysis for B lymphocytes (CD19, CD20, CD69), monocytes (CD14), NK cells
(CD56).

E.5.2.1

Timepoint(s) of evaluation of this end point

month 6

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

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

E.8.1.1

Randomised

E.8.1.2

Open

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.8.3

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

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

LPLV

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

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	445
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	445

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

2010-10-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-01-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2012-07-11

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