Safety, Tolerability, Efficacy and Optimal Dose Finding Study of BAF312 in Patients With Relapsing-remitting Multiple Sclerosis
Official Title
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.
Acronym
Not provided
Organization
NovartisINDUSTRY
Status Module
Record Verification Date
Dec 2019
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Mar 30, 2009Actual
Primary Completion Date
May 4, 2011Actual
Completion Date
May 4, 2011Actual
First Submitted Date
Apr 9, 2009
First Submission Date that Met QC Criteria
Apr 9, 2009
First Posted Date
Apr 10, 2009Estimated
Results Waived
Not provided
Results First Submitted Date
Oct 30, 2018
Results First Submitted that Met QC Criteria
Dec 26, 2019
Results First Posted Date
Jan 13, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jul 24, 2012
Certification/Extension First Submitted that Passed QC Review
Jul 24, 2012
Certification/Extension First Posted Date
Aug 1, 2012Estimated
Last Update Submitted Date
Dec 26, 2019
Last Update Posted Date
Jan 13, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Novartis PharmaceuticalsINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
The purpose of this study was to determine the dose-response curve for the MRI-based efficacy of BAF312 compared with placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), and to characterize its safety and tolerability for the selection of an optimal dose in a later phase III study.
Study Design Rationale An adaptive design was chosen to characterize the dose response curve of BAF312. In a first period of study ("Period 1"), three doses of BAF312 and placebo were tested for MRI efficacy. Based on an interim analysis (IA) after 3 months of treatment, two additional active doses for period 2 wereselected , thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. The doses were kept blinded. The use of Modeling and Simulation allowed to establish the full range and dynamics of the dose-response curve in silico, and hence the definition of the optimal dose for later phase III studies.
The choice of placebo as treatment control was essential to obtain information on the specific compared to non-specific effects of active treatment and provides the best way of evaluating the efficacy and of assessing the true safety and tolerability profile of BAF312. Short-term placebo exposure (6 (Period 1) or 3 (Period 2) months, respectively) was unlikely to lead to longer term differences in outcomes [Polman, 2008]. The use of an adaptive design strategy contributed to a significant reduction of placebo exposure, both in terms of the number of patients and duration, as compared to conventional trial models.
Patients having completed the study within the protocol might be eligible for the Extension Phase study where they receive long-term BAF312 treatment (a separate protocol).
Detailed Description
Not provided
Conditions Module
Conditions
Relapsing-remitting Multiple Sclerosis
Keywords
Multiple Sclerosis (MS)
Relapsing-Remitting
Demyelinating Autoimmune Diseases
Disseminated sclerosis
Encephalomyelitis disseminate
Inflammatory disease
Demyelination
Auto-inflammatory disease
Devic's disease
Balo concentric sclerosis
Schilder's diffuse sclerosis
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
297Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
BAF312 10mg (period 1)
Experimental
Drug: BAF312
BAF312 2 mg (period 1)
Experimental
Drug: BAF312
BAF312 0.5 mg (period 1)
Experimental
Drug: BAF312
BAF312 dose between 0.1 to 8 mg period 2
Experimental
Drug: BAF312
BAF312 dose between 0.1 - 8 mg period 2
Experimental
Drug: BAF312
Placebo (period 1, 2)
Placebo Comparator
Drug: Placebo
Interventions
Name
Type
Description
Arm Group Labels
Other Names
BAF312
Drug
BAF312 0.5 mg (period 1)
BAF312 10mg (period 1)
BAF312 2 mg (period 1)
BAF312 dose between 0.1 - 8 mg period 2
BAF312 dose between 0.1 to 8 mg period 2
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Dose Responsiveness of BAF312 Based on the Number of Combined Unique Active MRI Lesions (CUAL)
Combined unique active lesions (CUAL) were defined as new gadolinium [Gd]-enhanced lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions.
ED50 is the dose that gives half of the asymptotic maximum change over placebo. ED90 is the dose that gives 90% of the asymptotic maximum change over placebo.
3 months of treatment
Secondary Outcomes
Measure
Description
Time Frame
Number of Confirmed Relapses - Period 1
confirmed relapse: A relapse was to be confirmed by the Independent Evaluating Physician (examining neurologist) performing the EDSS. It was recommended that this occurred within 7 days of the onset of symptoms. A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the Expanded Disability Status Scale (EDSS) or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS).
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Key inclusion Criteria:
Diagnosis of Multiple Sclerosis (MS) as defined by revised McDonald criteria.
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 gadolinium (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.)
An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at randomization.
Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization.
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.
Key exclusion Criteria:
A manifestation of another type of MS than RRMS
History of chronic disease of the immune system other than MS
Malignancies, diabetes, significant cardiovascular, pulmonary and hepatic diseases and conditions
Mercier F, Bornkamp B, Ohlssen D, Wallstroem E. Characterization of dose-response for count data using a generalized MCP-Mod approach in an adaptive dose-ranging trial. Pharm Stat. 2015 Jul-Aug;14(4):359-67. doi: 10.1002/pst.1693. Epub 2015 Jun 17.
Selmaj K, Li DK, Hartung HP, Hemmer B, Kappos L, Freedman MS, Stuve O, Rieckmann P, Montalban X, Ziemssen T, Auberson LZ, Pohlmann H, Mercier F, Dahlke F, Wallstrom E. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013 Aug;12(8):756-67. doi: 10.1016/S1474-4422(13)70102-9. Epub 2013 Jun 11.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
Plan to Share IPD
Undecided
Description
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
One patient was misrandomized and never received study drug. Patient was included in Participant Flow and Baseline Characteristics but not included in actual enrollment count or Full Analysis Set..
Recruitment Details
The study was performed in 297 patients at 73 centers in 12 countries.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
BAF312 10mg (Period 1)
10 mg of BAF given orally o.d. for a period of 6 months
FG001
BAF312 2 mg (Period 1)
2 mg of BAF given orally o.d. for a period of 6 months
Proportion of Participants With Relapse-free Patients - Period 1 + 2
To explore the effect of BAF312 on the proportion of relapse-free patients (confirmed relapses only)
3 month
Proportion of Participants With Relapse-free Patients - Period 1 Only
To explore the effect of BAF312 on the proportion of relapse-free patients (confirmed relapses only)
6 months
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 +2 at Month 3
Results for Month 1 through Month 3 inclusive include patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan. The number of lesions of each type was available from the central MRI reader. No derivation was performed. Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
3 months
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 Only at 6 Months
Month 4 through Month 6 include patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
6 months
Number of All New Gd-enhanced T1 Lesions - Period 1 +2 at Month 3
The results for Month 1 through Month 3 includes patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
3 months
Number of All Gd-enhanced T1 Lesions - Period 1 Only at 6 Months
The results for Month 4 through Month 6 inclusive includes patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
6 months
Number of Monthly New/Enlarging T2 Lesions - Period 1 +2 at 3 Months
The results for Month 1 through Month 3 inclusive include patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
3 months
Number of Monthly New/Enlarging T2 Lesions - Period 1 Only at 6 Months
Month 4 through Month 6 inclusive include patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
6 months
Number of Patients Without Any New MRI Disease Activity - Period 1 +2
The proportion of patients who were free of new Gd-enhanced T1 lesions, and/or free of new or enlarging T2 lesions, i.e. free of new MRI activity (CUAL).
3 months
Number of Patients Without Any New MRI Disease Activity - Period 1 Only
The proportion of patients who were free of new Gd-enhanced T1 lesions, and/or free of new or enlarging T2 lesions, i.e. free of new MRI activity (CUAL).
6 months
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 +2 at 3 Months
In patients with high baseline disease activity, the relative reduction in new Gd-enhanced T1 lesions compared to placebo at Month 3.
High baseline disease activity is defined as >=2 Gd-enhanced T1 lesions at baseline.
The number of lesions of each type was available as such from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
3 months
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 Only at 6 Months
In patients with high baseline disease activity, the relative reduction in new Gd-enhanced T1 lesions compared to placebo at Month 6. High baseline disease activity is defined as >=2 Gd-enhanced T1 lesions at baseline.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
6 months
Number of CUAL - Period 1
Combined unique active lesions (CUAL) are defined as new Gd-enhanced T1 lesions or new or enlarging T2 lesions, withput double counting of lesions at any specific point in time.
6 months
Geometric Mean BAF312 Plasma Trough Concentrations
Geometric mean BAF312 plasma concentrations by treatment and by visit
Month 1, Month 3, Month 6
San Francisco
California
94143
United States
Novartis Investigative Site
Centennial
Colorado
80112
United States
Novartis Investigative Site
Miami
Florida
33136
United States
Novartis Investigative Site
Pompano Beach
Florida
33060
United States
Novartis Investigative Site
Tallahassee
Florida
32308
United States
Novartis Investigative Site
Tampa
Florida
33609
United States
Novartis Investigative Site
Chicago
Illinois
60637
United States
Novartis Investigative Site
Elk Grove Village
Illinois
60007
United States
Novartis Investigative Site
Grand Rapids
Michigan
49525
United States
Novartis Investigative Site
Raleigh
North Carolina
27607
United States
Novartis Investigative Site
Akron
Ohio
44320
United States
Novartis Investigative Site
Pittsburgh
Pennsylvania
15213
United States
Novartis Investigative Site
Greenville
South Carolina
29607
United States
Novartis Investigative Site
Seattle
Washington
98122
United States
Novartis Investigative Site
Milwaukee
Wisconsin
53215
United States
Novartis Investigative Site
Vancouver
British Columbia
V6T 1Z3
Canada
Novartis Investigative Site
Ottawa
Ontario
K1H 8L6
Canada
Novartis Investigative Site
Gatineau
Quebec
J9J 0A5
Canada
Novartis Investigative Site
Greenfield Park
Quebec
J4V 2J2
Canada
Novartis Investigative Site
Montreal
Quebec
H3A 2B4
Canada
Novartis Investigative Site
Helsinki
00930
Finland
Novartis Investigative Site
Tampere
FIN-33520
Finland
Novartis Investigative Site
Turku
20520
Finland
Novartis Investigative Site
Berlin
10713
Germany
Novartis Investigative Site
Berlin
13439
Germany
Novartis Investigative Site
Dresden
01307
Germany
Novartis Investigative Site
Freiburg im Breisgau
79106
Germany
Novartis Investigative Site
Leipzig
04103
Germany
Novartis Investigative Site
Lengerich
49525
Germany
Novartis Investigative Site
München
81675
Germany
Novartis Investigative Site
Münster
48149
Germany
Novartis Investigative Site
Wiesbaden
65191
Germany
Novartis Investigative Site
Budapest
1076
Hungary
Novartis Investigative Site
Budapest
1145
Hungary
Novartis Investigative Site
Debrecen
4032
Hungary
Novartis Investigative Site
Veszprém
H-8200
Hungary
Novartis Investigative Site
Montichiari
BS
25018
Italy
Novartis Investigative Site
Chieti
CH
66100
Italy
Novartis Investigative Site
Milan
MI
20132
Italy
Novartis Investigative Site
Roma
RM
00133
Italy
Novartis Investigative Site
Roma
RM
00152
Italy
Novartis Investigative Site
Roma
RM
00189
Italy
Novartis Investigative Site
Bergen
5021
Norway
Novartis Investigative Site
Drammen
3004
Norway
Novartis Investigative Site
Oslo
0424
Norway
Novartis Investigative Site
Lodz
90-153
Poland
Novartis Investigative Site
Lublin
20-954
Poland
Novartis Investigative Site
Warsaw
02-957
Poland
Novartis Investigative Site
Kazan'
420103
Russia
Novartis Investigative Site
Moscow
101990
Russia
Novartis Investigative Site
Moscow
119049
Russia
Novartis Investigative Site
Moscow
121359
Russia
Novartis Investigative Site
Moscow
125367
Russia
Novartis Investigative Site
Moscow
127018
Russia
Novartis Investigative Site
Moscow
129110
Russia
Novartis Investigative Site
Saint Petersburg
190013
Russia
Novartis Investigative Site
Saint Petersburg
197022
Russia
Novartis Investigative Site
Seville
Andalusia
41009
Spain
Novartis Investigative Site
Bilbao
Basque Country
48013
Spain
Novartis Investigative Site
Barcelona
Catalonia
08035
Spain
Novartis Investigative Site
Valencia
Valencia
46026
Spain
Novartis Investigative Site
Madrid
28040
Spain
Novartis Investigative Site
Basel
4031
Switzerland
Novartis Investigative Site
Bern
3010
Switzerland
Novartis Investigative Site
Lugano
6900
Switzerland
Novartis Investigative Site
Zurich
8091
Switzerland
Novartis Investigative Site
Ankara
06100
Turkey (Türkiye)
Novartis Investigative Site
Haseki / Istanbul
34096
Turkey (Türkiye)
Novartis Investigative Site
Istanbul
34093
Turkey (Türkiye)
Novartis Investigative Site
Izmir
35340
Turkey (Türkiye)
Novartis Investigative Site
Kocaeli
41380
Turkey (Türkiye)
FG002
BAF312 0.5 mg (Period 1)
0.5 mg of BAF given orally o.d. for a period of 6 months
FG003
Placebo (Period 1)
Placebo given orally o.d. for a period of 6 months
FG004
BAF312 1.25 mg (Period 2)
1.25 mg of BAF given orally o.d. for a period of 3 months
FG005
BAF312 0.25 mg (Period 2)
0.25 mg of BAF given orally o.d. for a period of 3 months
FG006
Placebo (Period 2)
Placebo given orally o.d. for a period of 3 months
FG00050 subjects
FG00149 subjects
FG00243 subjects
FG00346 subjects
FG00442 subjects
FG00551 subjects
FG00616 subjects
COMPLETED
FG00035 subjects
FG00144 subjects
FG00236 subjects
FG00342 subjects
FG00440 subjects
FG00550 subjects
FG00616 subjects
NOT COMPLETED
FG00015 subjects
FG0015 subjects
FG0027 subjects
FG0034 subjects
FG0042 subjects
FG0051 subjects
FG0060 subjects
Type
Comment
Reasons
Abnormal laboratory value(s)
FG0003 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
Administrative problems
FG0002 subjects
FG0011 subjects
FG0020 subjects
FG0031 subjects
FG004
Adverse Event
FG0006 subjects
FG0014 subjects
FG0023 subjects
FG0031 subjects
FG004
Protocol Violation
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0003 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
misrandomized (never received study med)
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
The Randomized Set (RAN) consisted of all patients who were assigned a randomization number. The RAN set was used for a summary of patient disposition and demographics and baseline characteristics. One patient was misrandomized and never received study drug. Demographic data was collected and the patient was included in the randomized set.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
BAF312 10mg (Period 1)
10 mg of BAF given orally o.d. for a period of 6 months
BG001
BAF312 2 mg (Period 1)
2 mg of BAF given orally o.d. for a period of 6 months
BG002
BAF312 0.5 mg (Period 1)
0.5 mg of BAF given orally o.d. for a period of 6 months
BG003
Placebo (Period 1)
Placebo given orally o.d. for a period of 3 months
BG004
BAF312 1.25 mg (Period 2)
1.25 mg of BAF given orally o.d. for a period of 3 months
BG005
BAF312 0.25 mg (Period 2)
0.25 mg of BAF given orally o.d. for a period of 3 months
BG006
Placebo (Period 2)
Placebo given orally o.d. for a period of 6 months
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00050
BG00149
BG00243
BG00346
BG00442
BG00551
BG00616
BG007297
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Randomized set
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00036.4± 8.43
BG00137.4± 8.94
BG00236.0± 8.79
BG003
Sex: Female, Male
Randomized set
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00030
BG00134
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Dose Responsiveness of BAF312 Based on the Number of Combined Unique Active MRI Lesions (CUAL)
Combined unique active lesions (CUAL) were defined as new gadolinium [Gd]-enhanced lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions.
ED50 is the dose that gives half of the asymptotic maximum change over placebo. ED90 is the dose that gives 90% of the asymptotic maximum change over placebo.
Full analysis set (FAS) consisted of all patients who received at least one dose of study medication and had no protocol deviation with severity code 0 or 8. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization.
Posted
Number
95% Confidence Interval
mg
3 months of treatment
ID
Title
Description
OG000
BAF312/Placebo
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).
Units
Counts
Participants
OG000296
Title
Denominators
Categories
Dose achieving 50% reduction
Title
Measurements
OG0000.51(0.19 to 1.34)
ED50
Title
Measurements
OG0000.83(0.30 to 2.27)
ED90
Secondary
Number of Confirmed Relapses - Period 1
confirmed relapse: A relapse was to be confirmed by the Independent Evaluating Physician (examining neurologist) performing the EDSS. It was recommended that this occurred within 7 days of the onset of symptoms. A relapse was confirmed when it was accompanied by an increase of at least half a step (0.5) on the EDSS or an increase of 1 point on two different Functional Systems (FS) of the Expanded Disability Status Scale (EDSS) or 2 points on one of the FS (excluding Bowel/Bladder or Cerebral FS).
Full analysis set in period I
Posted
Number
Confirmed relapses
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo given orally o.d.
Secondary
Proportion of Participants With Relapse-free Patients - Period 1 + 2
To explore the effect of BAF312 on the proportion of relapse-free patients (confirmed relapses only)
Full analysis set - Period I and II
Posted
Number
Proportion of participants
3 month
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 1.25 mg
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
OG005
Secondary
Proportion of Participants With Relapse-free Patients - Period 1 Only
To explore the effect of BAF312 on the proportion of relapse-free patients (confirmed relapses only)
Full analysis set - Period I One patient in the placebo group was misrandomized and never received study medication.
Posted
Number
proportion of participants
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo given orally o.d.
Units
Counts
Participants
Secondary
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 +2 at Month 3
Results for Month 1 through Month 3 inclusive include patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan. The number of lesions of each type was available from the central MRI reader. No derivation was performed. Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesion
3 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 1.25 mg
Secondary
Number of New [Gd]-Enhanced T1 Lesions Monthly - Period 1 Only at 6 Months
Month 4 through Month 6 include patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
lesions
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
Secondary
Number of All New Gd-enhanced T1 Lesions - Period 1 +2 at Month 3
The results for Month 1 through Month 3 includes patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesions
3 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 1.25 mg
Secondary
Number of All Gd-enhanced T1 Lesions - Period 1 Only at 6 Months
The results for Month 4 through Month 6 inclusive includes patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesions
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
Secondary
Number of Monthly New/Enlarging T2 Lesions - Period 1 +2 at 3 Months
The results for Month 1 through Month 3 inclusive include patients from both Period 1 and Period 2. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesions
3 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg (Period 1)
2 mg of BAF given orally o.d. for a period of 6 months
OG002
BAF312 1.25 mg
Secondary
Number of Monthly New/Enlarging T2 Lesions - Period 1 Only at 6 Months
Month 4 through Month 6 inclusive include patients from Period 1 only. New lesions at a specific visit were assessed relative to the previous scheduled visit scan.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesions
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
Secondary
Number of Patients Without Any New MRI Disease Activity - Period 1 +2
The proportion of patients who were free of new Gd-enhanced T1 lesions, and/or free of new or enlarging T2 lesions, i.e. free of new MRI activity (CUAL).
Full analysis set
Posted
Count of Participants
Participants
3 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 1.25 mg
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
Secondary
Number of Patients Without Any New MRI Disease Activity - Period 1 Only
The proportion of patients who were free of new Gd-enhanced T1 lesions, and/or free of new or enlarging T2 lesions, i.e. free of new MRI activity (CUAL).
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Count of Participants
Participants
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG003
Placebo
placebo given orally o.d.
Units
Counts
Secondary
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 +2 at 3 Months
In patients with high baseline disease activity, the relative reduction in new Gd-enhanced T1 lesions compared to placebo at Month 3.
High baseline disease activity is defined as >=2 Gd-enhanced T1 lesions at baseline.
The number of lesions of each type was available as such from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesions
3 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
Secondary
Number of Monthly New Gd-enhanced T1 Lesions With High Baseline Disease Activity - Period 1 Only at 6 Months
In patients with high baseline disease activity, the relative reduction in new Gd-enhanced T1 lesions compared to placebo at Month 6. High baseline disease activity is defined as >=2 Gd-enhanced T1 lesions at baseline.
The number of lesions of each type was available from the central MRI reader. No derivation was performed.
Lesion ratio (and 95% CI) is set between the estimated number of lesions on active treatment compared to placebo. Estimates are computed at Month 3 and Month 6. New lesions at a specific visit were assessed relative to the previous visit. The computation was based upon the mean number of monthly new [Gd]- enhanced lesions. Month 3 and Month 6 results are based on two negative binomial GEE regression models accounting for repeated measures on a patient. Both models were adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month interaction, using the log link.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
Lesions
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
Secondary
Number of CUAL - Period 1
Combined unique active lesions (CUAL) are defined as new Gd-enhanced T1 lesions or new or enlarging T2 lesions, withput double counting of lesions at any specific point in time.
Full analysis set One patient in the placebo group was misrandomized and never received study medication.
Posted
Mean
Standard Deviation
lesions
6 months
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo given orally o.d.
Units
Counts
Participants
Secondary
Geometric Mean BAF312 Plasma Trough Concentrations
Geometric mean BAF312 plasma concentrations by treatment and by visit
The PK Analysis Set consisted of all patients who received at least one dose of active BAF 312 study medication. Patients were analyzed according to the treatment received.
Posted
Mean
Standard Deviation
ng/ml
Month 1, Month 3, Month 6
ID
Title
Description
OG000
BAF312 10mg
10 mg of BAF given orally o.d.
OG001
BAF312 2 mg
2 mg of BAF given orally o.d.
OG002
BAF312 1.2.5 mg
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
Time Frame
Adverse Events (AEs) are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) up to approximately 2.5 years.
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
BAF312 10 mg
10 mg of BAF given orally o.d.
0
50
3
50
46
50
EG001
BAF312 2 mg
2 mg of BAF given orally o.d.
0
49
4
49
42
49
EG002
BAF312 1.25 mg
1.25 mg of BAF given orally o.d.
1
42
2
42
26
42
EG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
0
43
8
43
34
43
EG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
0
51
0
51
34
51
EG005
Placebo
Placebo given orally o.d.
0
61
0
61
45
61
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrioventricular block second degree
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0013 affected49 at risk
EG0020 affected42 at risk
EG0030 affected43 at risk
EG0040 affected51 at risk
EG0050 affected61 at risk
Bradycardia
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Death
General disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Perineal abscess
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Pyelonephritis acute
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Intentional overdose
Injury, poisoning and procedural complications
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Myopathy
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Benign intracranial hypertension
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Headache
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Multiple sclerosis relapse
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Optic neuritis
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Schizophreniform disorder
Psychiatric disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lymphopenia
Blood and lymphatic system disorders
MedDRA 13.1
Systematic Assessment
EG0005 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG0030 affected43 at risk
EG0040 affected51 at risk
EG0050 affected61 at risk
Atrioventricular block first degree
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Atrioventricular block second degree
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG00014 affected50 at risk
EG0013 affected49 at risk
EG0020 affected42 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0016 affected49 at risk
EG0023 affected42 at risk
EG003
Dry eye
Eye disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Eye pain
Eye disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Visual impairment
Eye disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0022 affected42 at risk
EG003
Abdominal pain lower
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Aphthous stomatitis
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Hypoaesthesia oral
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0008 affected50 at risk
EG0012 affected49 at risk
EG0023 affected42 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Asthenia
General disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Chills
General disorders
MedDRA 13.1
Systematic Assessment
EG0003 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Fatigue
General disorders
MedDRA 13.1
Systematic Assessment
EG0008 affected50 at risk
EG0014 affected49 at risk
EG0024 affected42 at risk
EG003
Hyperthermia
General disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Oedema peripheral
General disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Pyrexia
General disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Temperature intolerance
General disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Cystitis
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Influenza
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0014 affected49 at risk
EG0021 affected42 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0009 affected50 at risk
EG0016 affected49 at risk
EG0028 affected42 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0011 affected49 at risk
EG0022 affected42 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected49 at risk
EG0021 affected42 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0004 affected50 at risk
EG0012 affected49 at risk
EG0023 affected42 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0014 affected49 at risk
EG0021 affected42 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0012 affected49 at risk
EG0023 affected42 at risk
EG003
Epicondylitis
Injury, poisoning and procedural complications
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 13.1
Systematic Assessment
EG0003 affected50 at risk
EG0014 affected49 at risk
EG0021 affected42 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 13.1
Systematic Assessment
EG0004 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Systematic Assessment
EG0003 affected50 at risk
EG0012 affected49 at risk
EG0022 affected42 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Melanocytic naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0012 affected49 at risk
EG0021 affected42 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG00013 affected50 at risk
EG0015 affected49 at risk
EG0021 affected42 at risk
EG003
Headache
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG00023 affected50 at risk
EG00115 affected49 at risk
EG0025 affected42 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Migraine
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0003 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0014 affected49 at risk
EG0021 affected42 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Depression
Psychiatric disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Systematic Assessment
EG0004 affected50 at risk
EG0015 affected49 at risk
EG0021 affected42 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected49 at risk
EG0021 affected42 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0012 affected49 at risk
EG0020 affected42 at risk
EG003
Acne
Skin and subcutaneous tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0021 affected42 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA 13.1
Systematic Assessment
EG0001 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0020 affected42 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0011 affected49 at risk
EG0023 affected42 at risk
EG003
Hot flush
Vascular disorders
MedDRA 13.1
Systematic Assessment
EG0000 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Hypotension
Vascular disorders
MedDRA 13.1
Systematic Assessment
EG0002 affected50 at risk
EG0010 affected49 at risk
EG0020 affected42 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Point of Contact
Title
Organization
Phone
Extension
Email
Study Director
Novartis Pharmaceuticals
Novartis.email@novartis.com
ID
Term
D020529
Multiple Sclerosis, Relapsing-Remitting
D009103
Multiple Sclerosis
D003711
Demyelinating Diseases
D009471
Neuromyelitis Optica
D002549
Diffuse Cerebral Sclerosis of Schilder
Ancestor Terms
ID
Term
D020278
Demyelinating Autoimmune Diseases, CNS
D020274
Autoimmune Diseases of the Nervous System
D009422
Nervous System Diseases
D001327
Autoimmune Diseases
D007154
Immune System Diseases
D009188
Myelitis, Transverse
D009902
Optic Neuritis
D009901
Optic Nerve Diseases
D003389
Cranial Nerve Diseases
D005128
Eye Diseases
D001927
Brain Diseases
D002493
Central Nervous System Diseases
D056784
Leukoencephalopathies
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
C578989
siponimod
Ancestor Terms
Not provided
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
FG0060 subjects
2 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG0051 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
0 subjects
FG0050 subjects
FG0060 subjects
35.2
± 8.75
BG00435.4± 8.87
BG00537.4± 8.39
BG00635.9± 8.24
BG00736.3± 8.62
30
BG00336
BG00431
BG00542
BG0069
BG007212
Male
BG00020
BG00115
BG00213
BG00310
BG00411
BG0059
BG0067
BG00785
Title
Measurements
OG0007.46(2.72 to 20.47)
Units
Counts
Participants
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG0009
OG0015
OG00213
OG00313
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Mixed Models Analysis
Treatment compared to placebo based on negative binomial regression model, adjusted for treatment group and baseline number of relapses in prev 2 yrs.
0.148
Pairwise comparison and p-values refer to ARR on active treatment compared to placebo. An ARR-ratio <1 favors active treatment.
Negative binomial regression model
0.524
2-Sided
95
0.219
1.257
Superiority
An ARR-ratio <1 favors active treatment.
OG001
OG003
Mixed Models Analysis
Treatment compared to placebo based on negative binomial regression model, adjusted for treatment group and baseline number of relapses in prev 2 yrs.
0.041
Pairwise comparison and p-values refer to ARR on active treatment compared to placebo. An ARR-ratio <1 favors active treatment.
Negative binomial regression model
0.340
2-Sided
95
0.121
0.956
Superiority
OG002
OG003
Mixed Models Analysis
Treatment compared to placebo based on negative binomial regression model, adjusted for treatment group and baseline number of relapses in prev 2 yrs.
0.899
Pairwise comparison and p-values refer to ARR on active treatment compared to placebo. An ARR-ratio <1 favors active treatment.
Negative binomial regression model
1.051
2-Sided
95
0.486
2.273
Superiority
Placebo
Placebo given orally o.d.
Units
Counts
Participants
OG00050
OG00149
OG00242
OG00343
OG00451
OG00561
Title
Denominators
Categories
Title
Measurements
OG0000.87
OG0010.93
OG0020.93
OG0030.79
OG0040.86
OG0050.88
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Regression, Logistic
Proportions are estimated from the logistic regression model.
- An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
0.879
Logistic regression model
0.915
2-Sided
95
0.288
2.925
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG001
OG005
Regression, Logistic
0.399
Proportions are estimated from the logistic regression model.
- An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
Logistic regression model
1.745
2-Sided
95
0.484
7.167
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG002
OG005
Regression, Logistic
0.454
Proportions are estimated from the logistic regression model.
- An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
Logistic regression model
1.697
2-Sided
95
0.438
8.296
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG003
OG005
Regression, Logistic
0.223
Proportions are estimated from the logistic regression model.
- An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
Logistic regression model
0.509
2-Sided
95
0.166
1.511
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG004
OG005
Regression, Logistic
0.668
Proportions are estimated from the logistic regression model.
- An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
Logistic regression model
0.785
2-Sided
95
0.253
2.392
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG0000.84
OG0010.92
OG0020.77
OG0030.72
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Regression, Logistic
Proportions are estimated from the logistic regression model. - An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
0.178
Logistic regression model
1.996
2-Sided
95
0.731
5.669
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG001
OG003
Regression, Logistic
0.014
Proportions are estimated from the logistic regression model. - An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
Logistic regression model
4.120
2-Sided
95
1.328
14.681
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
OG002
OG003
Regression, Logistic
0.642
Proportions are estimated from the logistic regression model. - An odds ratio of > 1 indicates an increased odds in favor of the active treatment.
Logistic regression model
1.266
2-Sided
95
0.468
3.494
Other
Pairwise comparison of treatments to placebo are based on odds ratios estimated from a logistic regression model adjusted for treatment group and using number of relapses in the previous 2 years as a covariate.
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
OG005
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00242
OG00343
OG00451
OG00561
Title
Denominators
Categories
Title
Measurements
OG0000.2± 0.61
OG0010.4± 1.00
OG0020.2± 0.48
OG0030.9± 2.48
OG0040.6± 1.16
OG0051.4± 3.11
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Pairwise treatment comparison between different BAF312 dose groups and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
<0.001
lesion ratio
0.138
2-Sided
95
0.047
0.408
Superiority
OG001
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.012
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.307
2-Sided
95
0.123
0.771
Superiority
OG002
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.113
2-Sided
95
0.036
0.358
Superiority
OG003
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.021
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.375
2-Sided
95
0.163
0.860
Superiority
OG004
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.062
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.478
2-Sided
95
0.220
1.037
Superiority
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG0000.3± 0.57
OG0010.4± 0.96
OG0021.4± 4.17
OG0031.8± 3.09
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Regression, Logistic
new lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
<0.001
Lesion ratio
0.154
2-Sided
95
0.063
0.376
Superiority
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
OG001
OG003
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.005
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.228
2-Sided
95
0.081
0.641
Superiority
OG002
OG003
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.188
2-Sided
95
0.070
0.509
Superiority
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
OG005
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00242
OG00343
OG00451
OG00561
Title
Denominators
Categories
Title
Measurements
OG0000.5± 0.99
OG0010.8± 1.46
OG0020.3± 0.68
OG0031.5± 3.92
OG0041.0± 1.54
OG0052.0± 3.78
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Regression, Logistic
0.002
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.279
2-Sided
95
0.124
0.628
Superiority
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
OG001
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.019
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.396
2-Sided
95
0.182
0.861
Superiority
OG002
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.154
2-Sided
95
0.059
0.400
Superiority
OG003
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.035
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.454
2-Sided
95
0.219
0.945
Superiority
OG004
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.087
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.555
2-Sided
96
0.283
1.090
Superiority
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG0000.3± 0.77
OG0010.6± 1.37
OG0021.1± 3.78
OG0033.0± 5.88
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.095
2-Sided
95
0.033
0.273
Superiority
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
OG001
OG003
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.180
2-Sided
95
0.069
0.470
Superiority
OG002
OG003
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.173
2-Sided
95
0.069
0.434
Superiority
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
OG005
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00242
OG00343
OG00451
OG00561
Title
Denominators
Categories
Title
Measurements
OG0000.4± 0.99
OG0010.4± 1.00
OG0020.2± 0.64
OG0031.0± 3.08
OG0040.8± 1.39
OG0051.5± 3.17
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Regression, Logistic
0.005
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.259
2-Sided
95
0.100
0.670
Superiority
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
OG001
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.005
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.276
2-Sided
95
0.112
0.676
Superiority
OG002
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.118
2-Sided
95
0.034
0.409
Superiority
OG003
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.485
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.683
2-Sided
95
0.234
1.991
Superiority
OG004
OG005
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.142
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.591
2-Sided
95
0.292
1.193
Superiority
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG0000.4± 0.91
OG0010.4± 1.18
OG0020.9± 2.97
OG0032.1± 3.66
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Regression, Logistic
<0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model
lesion ratio
0.161
2-Sided
95
0.062
0.421
Superiority
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
OG001
OG003
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.001
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.197
2-Sided
95
0.074
0.527
Superiority
OG002
OG003
Pairwise treatment comparison between different BAF312 dose group and placebo used a two-sided significance level of 5% without adjusting for multiplicity.
Regression, Logistic
0.139
new Gd-enhanced T1 lesions was compared between treatment groups using a negative binomial generalized estimating equation regression model.
lesion ratio
0.416
2-Sided
95
0.130
1.331
Superiority
OG005
Placebo
Placebo given orally o.d.
Units
Counts
Participants
OG00050
OG00149
OG00242
OG00343
OG00451
OG00561
Title
Denominators
Categories
Title
Measurements
OG00015
OG00118
OG00220
OG00313
OG00420
OG00511
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Regression, Logistic
0.227
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
OG001
OG005
Regression, Logistic
0.020
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
OG002
OG005
Regression, Logistic
0.001
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
OG003
OG005
Regression, Logistic
0.122
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
OG004
OG005
Regression, Logistic
0.034
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
Participants
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG00012
OG00116
OG00211
OG0036
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Regression, Logistic
0.335
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
OG001
OG003
Regression, Logistic
0.022
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
OG002
OG003
Regression, Logistic
0.124
Calculated using weighted logistic regression model adj. for tx group and baseline number of Gd-enhanced T1 lesions. Weight used is equal to 1 if all post-baseline scans up to month 3 are available and (k-x)/k if x scans out of k scans are missing.
Superiority
BAF312 1.25 mg
1.25 mg of BAF given orally o.d.
OG003
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG004
BAF312 0.25 mg
0.25 mg of BAF given orally o.d.
OG005
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00242
OG00343
OG00451
OG00561
Title
Denominators
Categories
Title
Measurements
OG0000.5± 0.93
OG0010.5± 1.09
OG0020.1± 0.53
OG0031.5± 3.68
OG0041.5± 1.57
OG0052.7± 4.47
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG005
Regression, Logistic
0.006
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.129
2-Sided
95
0.030
0.561
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
OG001
OG005
Regression, Logistic
0.005
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.159
2-Sided
95
0.044
0.578
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
OG002
OG005
Regression, Logistic
0.005
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.052
2-Sided
95
0.007
0.405
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
OG003
OG005
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
Regression, Logistic
0.019
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.271
2-Sided
95
0.091
0.807
Superiority
OG004
OG005
Regression, Logistic
0.169
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.504
2-Sided
95
0.190
1.337
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
BAF312 0.5 mg
0.5 mg of BAF given orally o.d.
OG003
Placebo
Placebo-controlled
Units
Counts
Participants
OG00050
OG00149
OG00243
OG00345
Title
Denominators
Categories
Title
Measurements
OG0000.5± 0.69
OG0010.6± 1.16
OG0021.4± 4.26
OG0032.1± 2.42
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG003
Regression, Logistic
<0.001
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.214
2-Sided
95
0.091
0.499
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
OG001
OG003
Regression, Logistic
0.018
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.240
2-Sided
95
0.074
0.779
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.
OG002
OG003
Regression, Logistic
0.006
p-value corresponds to the lesion ratio and 95% CI of lesion ratio for active treatment in comparison to placebo.
lesion ratio
0.231
2-Sided
95
0.081
0.653
Superiority
Pairwise comparison of treatments are based on a negative binomial GEE regression model accounting for repeated measures on each patient, adjusted for baseline number of Gd-enhanced T1 lesions and treatment group x month (the month number of each lesion count measurement) interaction, using the log link.