Relapsing-remitting multiple sclerosis MedDRA version: 9.1 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis
Conditions
Interventions
Product Code: BAF312
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: BAF312
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Pharmaceutical form
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
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. 10. Is willing to refrain from submersion in water while wearing the MCT adherent device during dose titration 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 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Another type of MS than RRMS 2. History of chronic disease of the immune system other than MS, or a known immunodeficiency syndrome 3. Malignancy (except for successfully-treated basal or squamous cell carcinoma of skin) 4. Known, or ‘new’ diagnosis of diabetes mellitus (if screening blood glucose is suspicious for diabetes a patient should be further evaluated) 5. Macular edema during pre-randomization 6. Active systemic bacterial, viral or fungal infections, or AIDS, hepatitis B, hepatitis C infection defined as a positive HIV AB, hepatitis B surface AG or hepatitis C AB tests 7. Negative for varicella-zoster virus IgG AB at screening 8. Live or live attenuated vaccination within 2 m 9. Total lymphoid irradiation or bone marrow transplantation 10. Have been treated with: • ACTH or oral or injected corticosteroids within 1 m • IFN-ß or glatiramer acetate within 3 m • immunosuppressive medications such as azathioprine or methotrexate within 6 m • immunoglobulins and/or monoclonal ABs (including natalizumab) within 6 m (this rule does not apply for alemtuzumab, rituximab) • alemtuzumab, rituximab, cladribine, cyclophosphamide, mitoxantrone, or other immunosuppressive treatments with effects potentially lasting over 6 m, at any time 11. Any medically unstable condition, as assessed by the primary treating physician 12. Any of the following CV conditions • history or presence of stable or unstable IHD, MI, myocarditis or cardiomyopathy • history of Raynaud’s disease • cardiac failure (NYHA class II - IV) at screening and/or at baseline, or any severe cardiac disease as determined by the investigator • history of cardiac arrest • history of symptomatic bradycardia • resting pulse rate 440 msec on screening ECG • history or presence of symptomatic arrhythmia or arrhythmia requiring treatment or being otherwise of clinical significance • arterial hypertension, uncontrolled by medication • treatment with medication that impairs cardiac conduction • history of syncopes of suspected cardiac origin • history of catheter ablation 13. Any of the following pulmonary conditions: • severe respiratory disease or pulmonary fibrosis • tuberculosis, except for history of successfully treated TB or history of prophylactic treatment after positive PPD skin reaction • abnormal chest High Resolution Computer Tomography (HRCT), chest X-Ray or chest MRI suggestive of active pulmonary disease • abnormal Pulmonary Function Tests: forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) values lower than 70% of predicted value • patients receiving chronic (daily) therapies for asthma 14. Any of the following hepatic conditions: • chronic liver or biliary disease • total bilirubin >ULN unless in context of Gilbert’s syndrome • conjugated bilirubin >ULN • alkaline phosphatase (AP) >1.5 x ULN • AST or SGOT, ALT or SGPT >2 x ULN • GGT >3 x ULN 15. Any of the following abnormal laboratory values: • potassium >ULN • serum creatinine > 1.7 mg/dL (150 µmol/L) • white blood cell count < 3,500/mm3 (< 3.5 x 109/L) • lymphocyte count < 800/mm3 (< 0.8 x 109/L) 16. Any of the following neurological/psychiatric disorders: • history or presence of substance abuse (any illicit or prescription drugs or alcohol) • progressive neurological disorde
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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). ;Secondary Objective: • 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 ;Primary end point(s): Monthly number of combined unique active MRI lesions (CUAL) during 3 months of treatment. Combined unique active lesions are defined as new gadolinium [Gd]-enhancing lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions. | — |
Countries
Finland, Germany, Hungary, Italy, Spain
Outcome results
None listed