Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
- Registration Number
- NCT01185821
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study consisted of a two year dose blinded phase during which patients received one of five doses of siponimod (10, 2, 1.25, 0.5 or 0.25mg) following which patients were switched to open label treatment with siponimod 2mg for approximately a further 3 years. It will provide data on long term safety, tolerability and efficacy of siponimod in the RRMS patient population
- Detailed Description
This study was prematurely discontinued after approximately 5 years. The decision to prematurely discontinue the study was not taken due to safety-related concerns, rather due to a decision to focus the development of siponimod in MS on a different population.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 185
- Patients completed the core study BAF312A2201
- Written informed consent provided before any assessment of the extension study
- Female patients at risk of becoming pregnant must have a negative pregnancy test and use simultaneously two forms of effective contraception
- Newly diagnosed systemic disease other than MS (which may require immunosuppressive treatment)
- Malignancies, diabetes, significant cardiovascular and pulmonary diseases and conditions
- Active infections
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description BAF312 1.25 mg/2 mg BAF312 1.25 mg dose in Double Blind Phase and 2 mg in Open Label Phase BAF312 2 mg/2 mg BAF312 2 mg dose in Double Blind Phase and 2 mg in Open Label Phase BAF312 10 mg/2 mg BAF312 10 mg dose in Double Blind Phase and 2 mg in Open Label Phase BAF312 .5 mg/2 mg BAF312 .5 mg dose in Double Blind Phase and 2 mg in Open Label Phase BAF312 .25 mg/2 mg BAF312 .25 mg dose in Double Blind Phase and 2 mg in Open Label Phase
- Primary Outcome Measures
Name Time Method Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) Baseline Extension up to day 10 Number of patients with abnormal ECG conduction findings during dose-blinded titration at any visit post-dose, by type of abnormality and treatment (Extension Set). Number analyzed represent participants who had ECG results. Washout was defined as not being on treatment drug between Core and Extension for \>7 days. Abbreviation: Con=conduction, IVCD=intraventricular conduction defect , WPW=Wolff-Parkinson-White syndrome
Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout) Baseline Extension up to day 10 Number of patients with abnormal ECG conduction findings during dose-blinded titration at any visit post-dose, by type of abnormality and treatment (Extension Set). Number analyzed represent participants who had ECG results. Washout was defined as not being on treatment drug between Core and Extension for \>7 days. Abbreviations: washout = WO, Con=conduction
Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. Baseline up to approximately 5 years Refer to adverse events for complete listing of serious adverse events and other adverse events. Adverse events of interest were presented in separate tables. There were no reports of macular edema.
Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) Baseline Extension up to approximately 5 years Sitting blood pressure was measured in triplicate. The categories of notably low and high values and changes are presented for systolic (SBP) and diastolic (DBP). Multiple occurrences for a patient are counted as one occurrence in this table.
Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) Baseline Extension up to approximately 5 years Most infections were clinical diagnoses and were not confirmed by microbiology / virologic investigations. A patient with multiple occurrences of an infection for a preferred term is counted only once in each specific category.
Events identified as infections by the Investigator and defined as an AE with onset on or after the first dose of Extension Study drug up to and including 30 days after the date of the last doseNumber of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) Baseline Extension up to approximately 5 years
- Secondary Outcome Measures
Name Time Method Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set) Baseline extension up to approximately 5 years Group level ARR (raw) is calculated as the total number of relapses for all the patients in the treatment group divided by the total number of days on study for all patients in the group and multiplied by 365.25 to obtain the annual rate.
Model estimates are based on a negative binomial regression model, adjusted for treatment group, age, baseline EDSS, baseline number of Gd-enhanced T1 lesions and number of relapses in previous 2 years as covariates, with log(time on study in years) as the offset variable, using the log link.Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set) Baseline Extension up to approximately 5 years Six-month disability progression was defined relative to extension baseline EDSS score: 1.5 point increase in patients with baseline EDSS score of 0, 1.0 increase in patients with baseline EDSS score of between 0.5 to 5.0, inclusive and 0.5 increase in patients with baseline EDSS score of ≥ 5.5. The criteria for 6-month disability progression included detection of onset of progression and confirmation of progression for a period of at least 6 months.
Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) Baseline Extension up to approximately 5 years Free of MRI disease activity is defined as free of Gadolinium enhanced T1 lesions at any scan; free of new or enlarging T2 lesions at any scan: free of both gadolinium enhanced T1 lesions and new or enlarging T2 lesions at any scan. Number of patients analyzed = patients with at least one MRI scan during the specified time period. New lesions at a specific visit are assessed relative to the previous scheduled visit scan.
No imputation of missing scans is performed. As a result missing scans can lead to an overestimation of the proportion of patients free of a specific MRI activity.
Trial Locations
- Locations (1)
Novartis Investigative Site
🇹🇷Kocaeli, Turkey