Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
BAF312, siponimod, Multiple Sclerosis, Relapsing remitting Multiple Sclerosis, Demyelinating Autoimmune Diseases, MS, RRMS, inflammatory disease
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.
Interventions
DRUGBAF312
BAF312 was supplied in film-coated tablets in strengths of 5, 4 ,2, 1, .5 and .25 mg. The actual doses taken were 10, 2, 1.25, .5 and .25 mg taken orally once a day.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Masking continued during the double blind period of extension only.
Intervention model description
This extension study was originally set up as a 2 year dose-blinded extension study to maintain blinding of ongoing Core study. Study was later amended to include a subsequent Open-Label treatment phase after Core study was unblinded. During the Dose-Blinded phase of the extension study patients received the same dose from the Core study. Patients who received placebo in Period 1 during the Core Study were equally randomized to 1 of the 3 active doses of siponimod used during Period 1 (0.5, 2.0, or 10 mg) and patients who received placebo in Period 2 were equally randomized to 1 of the 2 active doses of siponimod used during Period 2 (0.25 mg or 1.25 mg).
Eligibility
Sex/Gender
ALL
Age
18 Years to 56 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* Newly diagnosed systemic disease other than MS (which may require immunosuppressive treatment) * Malignancies, diabetes, significant cardiovascular and pulmonary diseases and conditions * Active infections
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) | Baseline Extension up to approximately 5 years | — |
| 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 |
| 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 dose |
| 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 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Countries
Canada, Finland, Germany, Hungary, Italy, Norway, Poland, Russia, Spain, Switzerland, Turkey (Türkiye), United States
Participant flow
Recruitment details
All patients enrolled in the Extension study had completed the Core study. All patients underwent a 10 day titration at the start of the dose blinded phase of the study
Pre-assignment details
During the double blind phase of the extension study patients received the same dose from the Core study. Placebo patients from Core Period 1 were randomized to 0.5, 2 or 10mg, those from Period 2 were randomized to 0.25 or 1.25 mg. All patients received 2mg in Open Label phase (.5 and .25mg were titrated up to 2mg)
Participants by arm
| Arm | Count |
|---|---|
| BAF312 10 mg/2 mg 10 mg dose in Double Blind Phase and 2 mg in Open Label Phase | 33 |
| BAF312 2 mg/2 mg 2 mg dose in Double Blind Phase and 2 mg in Open Label Phase | 29 |
| BAF312 1.25 mg/2 mg 1.25 mg dose in Double Blind Phase and 2 mg in Open Label Phase | 43 |
| BAF312 .5 mg/2 mg .5 mg dose in Double Blind Phase and 2 mg in Open Label Phase | 29 |
| BAF312 .25 mg/2 mg .25 mg dose in Double Blind Phase and 2 mg in Open Label Phase | 50 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 1 | 2 | 1 | 0 | 0 |
| Overall Study | Abnormal test procedure result | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Administrative problems | 0 | 0 | 1 | 1 | 2 |
| Overall Study | Adverse Event | 2 | 3 | 1 | 2 | 5 |
| Overall Study | Condition no longer required study drug | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 3 | 0 | 9 |
| Overall Study | Lost to Follow-up | 1 | 1 | 2 | 1 | 2 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 2 | 1 | 3 |
Baseline characteristics
| Characteristic | BAF312 10 mg/2 mg | BAF312 2 mg/2 mg | BAF312 1.25 mg/2 mg | BAF312 .5 mg/2 mg | BAF312 .25 mg/2 mg | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 36.8 years STANDARD_DEVIATION 9.09 | 35.1 years STANDARD_DEVIATION 9.16 | 34.0 years STANDARD_DEVIATION 7.57 | 35.2 years STANDARD_DEVIATION 9.1 | 37.2 years STANDARD_DEVIATION 8.42 | 35.7 years STANDARD_DEVIATION 8.59 |
| Expanded disability status scale (EDSS) | 2.03 units on a scale STANDARD_DEVIATION 0.96 | 2.19 units on a scale STANDARD_DEVIATION 1.278 | 1.95 units on a scale STANDARD_DEVIATION 1.096 | 1.88 units on a scale STANDARD_DEVIATION 1.374 | 2.22 units on a scale STANDARD_DEVIATION 1.258 | 2.07 units on a scale STANDARD_DEVIATION 1.19 |
| Sex: Female, Male Female | 21 Participants | 18 Participants | 32 Participants | 18 Participants | 41 Participants | 130 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 11 Participants | 11 Participants | 9 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 33 | 26 / 29 | 42 / 43 | 29 / 29 | 42 / 50 | 169 / 184 |
| serious Total, serious adverse events | 4 / 33 | 7 / 29 | 6 / 43 | 6 / 29 | 8 / 50 | 31 / 184 |
Outcome results
Primary
Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout)
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
Time frame: Baseline Extension up to day 10
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAF312 10 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Con:1st degree AV block | 0 participants |
| BAF312 10 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction-Prolonged QTc | 5 participants |
| BAF312 10 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - WPW | 0 participants |
| BAF312 10 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - IVCD | 3 participants |
| BAF312 10 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - AV Mobitz I | 1 participants |
| BAF312 2 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Con:1st degree AV block | 1 participants |
| BAF312 2 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - AV Mobitz I | 0 participants |
| BAF312 2 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - IVCD | 8 participants |
| BAF312 2 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - WPW | 0 participants |
| BAF312 2 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction-Prolonged QTc | 2 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - AV Mobitz I | 0 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction-Prolonged QTc | 5 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - IVCD | 1 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Con:1st degree AV block | 1 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - WPW | 0 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - WPW | 1 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction-Prolonged QTc | 2 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Con:1st degree AV block | 1 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - AV Mobitz I | 0 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - IVCD | 3 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - AV Mobitz I | 0 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Con:1st degree AV block | 1 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction-Prolonged QTc | 4 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - WPW | 0 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout) | Conduction - IVCD | 0 participants |
Primary
Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout)
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
Time frame: Baseline Extension up to day 10
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAF312 10 mg/2 mg | Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout) | 4 participants |
Primary
Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set)
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.
Time frame: Baseline Extension up to approximately 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP Low: ≤ 90 | 1 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 decrease from baseline | 8 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP High: ≥ 160 | 1 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 increase from baseline | 9 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP Low: ≤ 50 | 1 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 decrease from baseline | 14 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP High: ≥ 100 | 4 participants |
| BAF312 10 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 increase from baseline | 9 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP High: ≥ 160 | 1 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 decrease from baseline | 8 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP Low: ≤ 90 | 3 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 increase from baseline | 8 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 decrease from baseline | 10 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 increase from baseline | 13 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP Low: ≤ 50 | 0 participants |
| BAF312 2 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP High: ≥ 100 | 7 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP High: ≥ 100 | 4 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 increase from baseline | 13 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 increase from baseline | 12 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 decrease from baseline | 10 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP High: ≥ 160 | 1 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 decrease from baseline | 4 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP Low: ≤ 90 | 2 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP Low: ≤ 50 | 1 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 decrease from baseline | 6 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP High: ≥ 160 | 3 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 increase from baseline | 13 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP Low: ≤ 50 | 0 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 decrease from baseline | 10 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 increase from baseline | 11 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP Low: ≤ 90 | 1 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP High: ≥ 100 | 4 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 increase from baseline | 18 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 increase from baseline | 17 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP High: ≥ 160 | 3 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP High: ≥ 100 | 4 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP Low: ≤ 90 | 1 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP ≥ 15 decrease from baseline | 10 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | SBP ≥ 20 decrease from baseline | 10 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set) | DBP Low: ≤ 50 | 1 participants |
Primary
Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set)
Time frame: Baseline Extension up to approximately 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAF312 10 mg/2 mg | Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) | 1 participants |
| BAF312 2 mg/2 mg | Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) | 0 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) | 1 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) | 0 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set) | 1 participants |
Primary
Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set)
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 dose
Time frame: Baseline Extension up to approximately 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAF312 10 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Oral herpes | 5 participants |
| BAF312 10 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Influenza | 3 participants |
| BAF312 10 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Herpes zoster | 5 participants |
| BAF312 2 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Herpes zoster | 0 participants |
| BAF312 2 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Oral herpes | 0 participants |
| BAF312 2 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Influenza | 4 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Herpes zoster | 3 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Oral herpes | 4 participants |
| BAF312 1.25 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Influenza | 3 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Oral herpes | 2 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Influenza | 6 participants |
| BAF312 .5 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Herpes zoster | 2 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Herpes zoster | 0 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Oral herpes | 4 participants |
| BAF312 .25 mg/2 mg | Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set) | Influenza | 6 participants |
Primary
Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study.
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.
Time frame: Baseline up to approximately 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAF312 10 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Serious adverse events | 4 events |
| BAF312 10 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Other adverse events | 30 events |
| BAF312 2 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Serious adverse events | 7 events |
| BAF312 2 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Other adverse events | 26 events |
| BAF312 1.25 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Serious adverse events | 6 events |
| BAF312 1.25 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Other adverse events | 42 events |
| BAF312 .5 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Other adverse events | 29 events |
| BAF312 .5 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Serious adverse events | 6 events |
| BAF312 .25 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Serious adverse events | 8 events |
| BAF312 .25 mg/2 mg | Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study. | Other adverse events | 42 events |
Secondary
Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set)
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.
Time frame: Baseline extension up to approximately 5 years
| Arm | Measure | Value (MEAN) |
|---|---|---|
| BAF312 10 mg/2 mg | Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set) | 0.18 Group level ARR |
| BAF312 2 mg/2 mg | Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set) | 0.15 Group level ARR |
| BAF312 1.25 mg/2 mg | Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set) | 0.16 Group level ARR |
| BAF312 .5 mg/2 mg | Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set) | 0.19 Group level ARR |
| BAF312 .25 mg/2 mg | Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set) | 0.22 Group level ARR |
Secondary
Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set)
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.
Time frame: Baseline Extension up to approximately 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BAF312 10 mg/2 mg | Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set) | 72.3 percentage of participants |
| BAF312 2 mg/2 mg | Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set) | 82.4 percentage of participants |
| BAF312 1.25 mg/2 mg | Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set) | 84.8 percentage of participants |
| BAF312 .5 mg/2 mg | Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set) | 81.4 percentage of participants |
| BAF312 .25 mg/2 mg | Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set) | 78.6 percentage of participants |
Secondary
Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set)
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.
Time frame: Baseline Extension up to approximately 5 years
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BAF312 10 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 lesions at any scan | 58.1 percentage of participants |
| BAF312 10 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 and new enlarged T2 lesions | 32.3 percentage of participants |
| BAF312 10 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of new/enlarging T2 lesions at any scan | 32.3 percentage of participants |
| BAF312 2 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of new/enlarging T2 lesions at any scan | 42.3 percentage of participants |
| BAF312 2 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 lesions at any scan | 57.7 percentage of participants |
| BAF312 2 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 and new enlarged T2 lesions | 42.3 percentage of participants |
| BAF312 1.25 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of new/enlarging T2 lesions at any scan | 46.5 percentage of participants |
| BAF312 1.25 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 lesions at any scan | 58.1 percentage of participants |
| BAF312 1.25 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 and new enlarged T2 lesions | 44.2 percentage of participants |
| BAF312 .5 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 lesions at any scan | 44.8 percentage of participants |
| BAF312 .5 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 and new enlarged T2 lesions | 20.7 percentage of participants |
| BAF312 .5 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of new/enlarging T2 lesions at any scan | 20.7 percentage of participants |
| BAF312 .25 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of new/enlarging T2 lesions at any scan | 40.4 percentage of participants |
| BAF312 .25 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 lesions at any scan | 66.0 percentage of participants |
| BAF312 .25 mg/2 mg | Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set) | Free of Gd-enhanced T1 and new enlarged T2 lesions | 40.4 percentage of participants |