Clinical Trials Register

Summary
EudraCT Number:	2011-002969-38
Sponsor's Protocol Code Number:	CFTY720DDE07
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:	2011-09-30
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

2011-002969-38

A.3

Full title of the trial

A 6-month, multicenter, randomized, controlled parallel group study to evaluate the effect of physical training on fatigue in patients with relapsing-remitting multiple sclerosis treated with fingolimod (Gilenya®), followed by a 6 month optional extension phase

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

CFTY720DDE07

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	004991127313135
B.5.5	Fax number	004991127317135
B.5.6	E-mail	katrin.schuh@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role
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

Fatigue 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	14.1
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 effect of structured physical e-training vs. no training on fatigue in Gilenya-treated RRMS patients after 6 months; assessed by the mFIS fatigue scale.

E.2.2

Secondary objectives of the trial

• To evaluate the effect of structured physical e-training vs. no training on isometric and dynamic muscular strength measured by Isomed 2000 isometric measurement device (knee flexion/tension, trunk flexion/extension) and sit-to-stand-test.
• To evaluate the effect of structured physical e-training vs. no training on quality of life assessed by Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS)
• To evaluate the effect of structured physical e-training vs. no training on fatigue parameters assessed by the WEIMuS
• To evaluate the effect of structured physical e-training vs. no training on depression assessed by the BDI-II
• To evaluate the effect of structured physical e-training vs. no training on aerobic capacity measured by a graded exercise test on a treadmill using spiroergometry

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 MS defined by 2010 revised McDonald criteria (see Appendix 5).
4. Patients with Expanded Disability Status Scale (EDSS) score of 0-3.5 (including) (see Appendix 7).
5. Immunomodulatory treatment with prescribed fingolimod for at least one month prior to baseline
6. Fatigue score assessed by mFIS of equal or greater than 14 at screening
7. Willingness to participate in a structured interventional training program according to the study protocol
8. Neurologically stable with no evidence of relapse within 30 days prior to inclusion date
9. Sufficient ability to read, to write, to understand, to communicate also electronically, and to have access to world wide web.

E.4

Principal exclusion criteria

1. Patients who have been treated with:
• systemic corticosteroids or immunoglobulins within 1 month prior to randomization;
• immunosuppressive medications such as azathioprine, cyclophosphamide, or methotrexate within 3 months prior to randomization;
• monoclonal antibodies (including natalizumab) within 3 months prior to randomization;
• mitoxantrone within 6 months prior to randomization
• 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 cardiac arrest;
• history of myocardial infarction or with current unstable ischemic heart disease;
• history of angina pectoris due to coronary spasm or history of Raynaud syndrome
• Heart failure (NYHA III-IV) or any severe cardiac disease as determined by the
investigator;
• history or presence of a second-degree AV block, Type II or a third-degree AV
Blockor an increased QTc interval >450 ms in males and in females corrected using
Bazett’s formula.
• patients receiving Class Ia (ajmaline, disopyramide, procainamide, quinidine) or
III antiarrhythmic drugs (e.g., amiodarone, bretylium, sotalol, ibulitide, azimilide,
dofelitide);
• patients receiving beta-blockers
• proven history of sick sinus syndrome or sino-atrial heart block;History of symptomatic bradycardia or recurrent syncope, cerebrovascular disease, hypokalaemia, congestive heart failure or severe sleep apnea
• uncontrolled hypertension
• resting heart reate 􀵑 45 bpm
4. Patients with severe respiratory disease, pulmonary fibrosis, or chronic obstructive
pulmonary disease (Class III-IV).
5. Patients with any of the following neurologic/psychiatric disorders:
• current substance abuse (drug or alcohol) 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.
6. Clinically relevant internal disease (e.g. uncorrected anemia) or orthopedic diseases (e.g. scoliosis) that might interfere with physical training
7. Any severe disability or clinical impairment that can prevent the patient to meet all study requirements at the investigator`s discretion
8. Patients who have received an investigational drug (excluding fingolimod) or therapy within 90 days or 5 half-lives of randomization, 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 laboratory

E.5 End points

E.5.1

Primary end point(s)

To decrease the level of fatigue via a structured physical e-training vs. no training in Gilenya-treated RRMS patients after 6 months; assessed by the mFIS fatigue scale.

E.5.1.1

Timepoint(s) of evaluation of this end point

after 6 and 12 months

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

after 6 and 12 months

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

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

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

Yes

E.8.2.3.1

Comparator description

Training versus waiting group with delayed start of training after 6 months

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

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

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

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:

226

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

226

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

2011-10-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-11-08

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-07-14

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