| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| treating of cognitive symptoms in relapsing-remitting multiple sclerosis |
| Behandlung kognitiver Symptome bei der schubförmigen remittierenden Multiplen Sklerose |
|
| E.1.1.1 | Medical condition in easily understood language |
| Multiple Sclerosis |
| Multiple Sklerose |
|
| 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 | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| The primary objective of this pilot study is to evaluate, by means of a specific cognitive test battery (Brief Repeatable Battery and Delis-Kaplan Executive Function System scale - Sorting Test), the slowing/reduction of cognitive dysfunction progression in RRMS patients after 18 months of treatment with fingolimod in comparison with interferon beta 1b treatment, and to evaluate which test of the battery is the most sensitive in detecting differences between treatment groups. |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate: how the effects on cognitive dysfunction progression are associated to the effect of slowing the brain volume reduction at MRI that DMDs might have in RRMS patients, in the brain as a whole and in specific brain regions. In a subgroup of patients/sites, if and to what extent optical nerve atrophy as assessed by the RNFL thickness at the Spectralis OCT is predictive of the atrophy of the relevant brain regions and of cognitive deterioration and to what extent this is affected by DMD treatment. If fingolimod has effects on depression in MS, how the effects of fingolimod and IFN beta 1b on brain atrophy, on cognitive dysfunction progression and on depression in MS are associated. Changes in QoL, by mean of the MSQoL54, upon initiation of treatment with fingolimod 0.5 mg. Changes in fatigue. Impact of cognitive symptoms on patient work, financial status, assistance required, social activity. Evaluation in a subgroup how the SSTT correlates with results of the BRB or D-KEFS. |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
| OCT-(Optical Coherence Tomography)-substudy |
|
| E.3 | Principal inclusion criteria |
| 1. Written informed consent must be obtained before any assessment is performed. 2. Male or female subjects aged 18-60 years. 3. Patients with relapsing-remitting forms of MS (RRMS) defined by 2005 revised McDonald criteria (McDonald et al 2001; Polman et al 2005). 4. Patients with active disease, defined as at least one clinical relapse in the last year, or two clinical relapses in the last two years if there are signs of disease activity at one brain MRI scan performed in the last six months. 5. Patients with cognitive impairment at screening, defined as at least one test of the Rao’s Brief Repeatable Battery (BRB) with scores falling below the 10th percentile of the normative data (age- and gender-based). |
|
| E.4 | Principal exclusion criteria |
Patients who had already been treated with multiweekly interferon and had an unsatisfactory response according to the judgment of the investigator. Patients with hyperactive forms of the MS disease according to the judgment of the investigator. Patients with an EDSS>5. Patients with an acute relapse of MS. Patients with a prior or current diagnosis of Major Depression according to DSM-IV. Patients with a history of chronic disease of the immune system other than MS, atopic dermatitis, psoriasis or Hashimoto's Disease. History of malignancy of any organ system, within the past 5 years. Patients with uncontrolled diabetes mellitus (HbA1c >7%). Diagnosis of macular edema during Screening Phase. 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. Patients with negative test for varicella-zoster virus IgG antibodies at screening. If these patients elect to be vaccinated, they may return to be rescreened at least two month after the vaccination. Have received any live or live attenuated vaccines within 2 months prior to baseline. Patients who have received total lymphoid irradiation or bone marrow transplantation. Patients who have been treated with:corticosteroids (systemic) or ACTH within 1 month prior to screening; immunosuppressive medications such as azathioprine or methotrexate within 3 months prior to baseline;immunoglobulins and/or monoclonal antibodies within 3 months prior to baseline;cladribine, cyclophosphamide any time, mitoxantrone in the last 12 month. Patients with any medically unstable condition, as assessed by the primary treating physician at each site. Patients with any of the following cardiovascular conditions or conditions for which significant bradycardia may be poorly tolerated: history of cardiac arrest; history of myocardial infarction or with known ischemic heart disease (including angina pectoris); history of symptomatic bradycardia or recurrent syncope;
cerebrovascular disease; congestive heart failure; severe untreated sleep apnea;known history of angina pectoris due to coronary spasm or history of Raynaud’s phenomenon; cardiac failure at time of Screening (Class III) or any severe cardiac disease as determined by the investigator; history or presence of a Mobitz 2 second degree AV block or a third degree AV block or an increased QTc interval >450 ms in males and >470 ms in females corrected using Bazett’s formula; patients receiving Class Ia and III antitiarrhythmic drugs; patients receiving heart rate lowering drugs, e.g. beta-blockers, calcium channel blockers (e.g. verapamil, diltiazem or ivabradine) or other substances which may decrease heart rate (e.g. digoxin, anticholinesteratic agents or pilocarpine); resting pulse rate <45 bpm prior to baseline;proven history of sick sinus syndrome or sino-atrial heart block; hypertension, not controlled by prescribed medications. Patients with any of the following pulmonary conditions:pulmonary fibrosis;active tuberculosis. Patients with any of the following hepatic conditions:chronic liver or biliary disease;total bilirubin greater than 2 times the upper limit of the normal range, unless in context of Gilbert’s syndrome; conjugated bilirubin greater than 2 times the upper limit of the normal range;AST, ALT >2 times the upper limit of the normal range; AP >1.5 times the upper limit of the normal range; GGT >3 times the upper limit of the normal range. Patients with any of the abnormal laboratory values: serum creatinine >1.7 mg/dL (150 μmol/L);WBC count <3,500/mm3 or lymphocyte count <800/mm3. Patients with any of the following disorders:history of substance abuse in the past 5 years or 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. Participation in any clinical research study within 6 months prior to baseline. Pregnant or nursing 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 (> 5 mIU/ml). Women of child-bearing potential UNLESS they are using two birth control methods. History of hypersensitivity to the study drug or to drugs of similar chemical classes. Prior intake of fingolimod e.g. as study medication or as commercially available drug (Gilenya). Prior participation in a clinical trial with other S1P-receptor modulators e.g. BAF312. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of the study is to evaluate the reduction of cognitive dysfunction progression in RRMS patients after 18 months of treatment with fingolimod in comparison with interferon beta 1b treatment and to evaluate which test is most sensitive in detecting differences between treatment groups. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
| To evaluate: how the effects on cognitive dysfunction progression are associated to the effect of slowing the brain volume reduction at MRI that DMDs might have in RRMS patients, in the brain as a whole and in specific brain regions. In a subgroup of patients/sites, if and to what extent optical nerve atrophy as assessed by the RNFL thickness at the Spectralis OCT is predictive of the atrophy of the relevant brain regions and of cognitive deterioration and to what extent this is affected by DMD treatment. If fingolimod has effects on depression in MS and how the effects of fingolimod and interferon beta 1b on brain atrophy, on cognitive dysfunction progression and on depression in MS are associated. Changes in quality of life, by mean of the MSQoL54 scale, upon initiation of treatment with fingolimod 0.5 mg. Changes in fatigue. Impact of cognitive symptoms on patient work and financial status, assistance required and social activity, by means of ESS. Evaluation in a subgroup of patients / sites how the Symbol Symbol Transcode Test (SSTT) correlates with results of the BRB or D-KEFS. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| 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 | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| 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 | 8 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 30 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | No |
| 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
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 5 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
| E.8.9.2 | In all countries concerned by the trial months | 5 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
