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

• Register: EUCTR
• Last refreshed on: 24 July 2012
• Main ID: EUCTR2011-002969-38-DE
• Date of registration: 30/09/2011
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma GmbH
• Public title: 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
• Scientific title: 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 -
• Date of first enrolment: 08/11/2011
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002969-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Training versus waiting group with delayed start of training after 6 months Number of treatment arms in the trial: 2

Countries of recruitment

Germany

Contacts

• Name: Project Leader
• Affiliation: Novartis Pharma GmbH

• Name: Project Leader
• Affiliation: Novartis Pharma GmbH

Key inclusion & exclusion criteria

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.

Are the trial subjects under 18? no
Number of subjects for this age range:
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) no
F.1.3.1 Number of subjects for this age range

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




Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Fatigue in Patients with relapsing remitting Multiple Sclerosis
MedDRA version: 14.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: Gilenya
Product Name: Fingolimod
Product Code: FTY720
Pharmaceutical Form: Capsule, hard
CAS Number: 162359-56-0
Current Sponsor code: FTY720
Other descriptive name: Fingolimod Hydrochloride
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Primary Outcome(s)

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.

Main Objective: 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.

Secondary Objective: • 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

Timepoint(s) of evaluation of this end point: after 6 and 12 months

Secondary Outcome(s)

Secondary end point(s): • 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

Timepoint(s) of evaluation of this end point: after 6 and 12 months

Secondary ID(s)

CFTY720DDE07

Source(s) of Monetary Support

Novartis pharma GmbH