| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10028245 |
| E.1.2 | Term | Multiple sclerosis |
|
| 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 study is to evaluate the dose response relationship among five doses of BAF312 and placebo during 3 months of treatment in patients with RRMS, as measured by the number of combined unique active [MRI] lesions (CUAL). |
|
| E.2.2 | Secondary objectives of the trial |
| To evaluate the safety and tolerability (including blood pressure effects) of BAF312 during 6 months and 3 months of treatment in MS patients To evaluate the dose response relationship of BAF312 and placebo during 6 months of treatment in patients with RRMS, as measured by CUAL To explore the effect of BAF312 on the number of relapses and thereof derived measures (e.g. annualized relapse rate (ARR), proportion of relapse-free patients) To explore the correlation of the course of the lymphocyte count with paraclinical (MRI activity) and clinical course |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| Inclusion criteria 1. Patients must give written informed consent before any assessment is performed 2. 18 through 55 years of age inclusive 3. Male or female 4. Females of childbearing potential: must have a negative pregnancy test at Baseline prior to entry into the double-blind treatment phase must simultaneously use two forms of effective contraception (either partner) during the treatment and for one months or one menstrual cycle, whichever is longer after discontinuation of the study drug if either post-menopausal for 12 months prior to randomization or surgically sterile (through hysterectomy or bilateral oophorectomy, if documented), are not required to use birth control (refer to Section 8.3 for more details) 5. Diagnosis of MS as defined by revised McDonald criteria (see Appendix 4) 6. A relapsing-remitting course of disease with at least 1 documented relapse during the previous year, or 2 documented relapses during the previous 2 years, or a positive Gd-enhanced MRI scan at screening (in case the first MRI scan obtained at screening is negative, a second scan may be obtained 1 month later) 7. An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at randomization 8. Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization 9. Patients who decline initiation or continuation of treatment with available disease modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator. |
|
| E.4 | Principal exclusion criteria |
| Exclusion criteria 1. A manifestation of another type of MS than RRMS 2. History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome 3. History or presence of malignancy (except for successfully-treated basal or squamous cell carcinoma of skin) 4. A known, or ‘new’ diagnosis of diabetes mellitus (if screening blood glucose is suspicious for diabetes [&#8805; 126 mg/dL or &#8805; 7 mmol/L if fasting; &#8805; 200 mg/dL or 11.1 mmol/L if random testing] a patient should be further evaluated for diabetes mellitus) 5. Diagnosis of macular edema during pre-randomization 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 examination at the Screening Visit) 6. Active systemic bacterial, viral or fungal infections, or diagnosis of AIDS, Hepatitis B, Hepatitis C infection defined as a positive HIV antibody, Hepatitis B surface antigen or Hepatitis C antibody tests, respectively 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 2 months prior to randomization 9. Have received total lymphoid irradiation or bone marrow transplantation 10. Have been treated with: corticosteroids or ACTH within 1 month prior to randomization IFN-&#946; or glatiramer acetate within 3 months prior to randomization immunosuppressive medications such as azathioprine or methotrexate within 6 months prior to randomization immunoglobulins and/or monoclonal antibodies (including natalizumab) within 6 months prior to randomization (this rule does not apply for alemtuzumab, rituximab, see below) alemtuzumab, rituximab, cladribine, cyclophosphamide, mitoxantrone, or other immunosuppressive treatments with effects potentially lasting over 6 months, at any time 11. Any medically unstable condition, as assessed by the primary treating physician 12. Any of the following cardiovascular conditions: myocardial infarction within the past 6 months prior to enrollment or current unstable ischemic heart disease history of Raynaud’s disease cardiac failure at time of Screening (Class III, according to NYHA Classification; Appendix 4) or any severe cardiac disease as determined by the investigator history of cardiac arrest history of symptomatic bradycardia resting pulse rate < 55 bpm prior to randomization history of sick sinus syndrome or sino-atrial heart block history or presence of a second degree AV block or a third degree AV block or an increased QTc interval > 440 msec on screening electrocardiogram (ECG) arrhythmia requiring current treatment with Class III anti-arrhythmic drugs (e.g.amiodarone, bretylium, sotalol, ibulitide, azimilide, dofelitide) hypertension, uncontrolled by medication |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| The primary objective of this study is to evaluate the dose response relationship among five doses of BAF312 and placebo during 3 months of treatment in patients with RRMS, as measured by the number of combined unique active [MRI] lesions (CUAL). |
|
| 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 | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Yes |
| E.8.2.3.1 | Comparator description |
| - same IMP used at different dosage |
|
| 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 | 6 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 34 |
| 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 | Information not present in EudraCT |
| 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 |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
