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 sclerosis; MedDRA version: 9.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosis

• Registration Number: EUCTR2008-008719-25-FI
• Lead Sponsor: ovartis Pharma Services AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-02-19
• Last Update Posted: 1 May 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 275

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.

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

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 [= 126 mg/dL or = 7 mmol/L if fasting; = 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-ß 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 cardiovascular conditions listed in the exlusion criteria of the protocol
13. Any of the pulmonary conditions listed in the exclusion criteria of the protocol
14. Any of the hepatic conditions listed in the exlusion criteria of the protocol
15. Any of the abnormal laboratory values listed in the exlusion criteria of the protocol
16. Any of the neurological/psychiatric disorders listed in the exlusion criteria of the protocol
17. Unable to undergo MRI scans due to claustrophobia or metallic implants incompatible with MRI
18. Unable to receive gadolinium-based MRI contrast agents due to a history of hypersensitivity to gadolinium-based contrast agents, or severe renal insufficiency
19. Participation in any clinical research study evaluating another investigational drug or therapy within 3 months prior to randomization
20. History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes
21. Homozygosity for CYP2C9*3 (will be tested at Screening), and refusal to test for CYP2C9*3 haplotype
22. Patients using (or having used within four (4) weeks or 5 half- lives, whichever is greater before initial dosing) concomitant medications that are strong or moderate inhibitors or inducers of CYP2C9 (see Appendix 3 for a list of medications that are not allowed during the study).
23. 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 human chorionic gonadotropin la

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified