A phase II, double-blind, randomized, multi-center, adaptive dose-ranging, placebo-controlled, parallel-group study evaluating safety, tolerability and efficacy on MRI lesion parameters and determining the dose response curve of BAF312 given orally once daily in patients with relapsing-remitting multiple sclerosis
- Conditions
- Relapsing-remitting multiple sclerosisMedDRA version: 9.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosis
- Registration Number
- EUCTR2008-008719-25-DE
- Lead Sponsor
- ovartis Pharma Services AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 275
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
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 < 55 bpm
• history or presence of a clinically relevant impairment of cardiac conduction including sick sinus syndrome, sino-atrial block
• clinically significant AVB, bundle branch block or an increased QTc interval > 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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method