Trial · NCT01665144
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
NCT01665144, Phase 3, Completed, Novartis Pharmaceuticals; results first posted 2018-10-31
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND). Trials, record NCT01665144. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT01665144
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
- NCT number
- NCT01665144
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 1,651 participants, actual
- Lead sponsor
- Novartis Pharmaceuticals
- Conditions
- Secondary Progressive Multiple Sclerosis
- Interventions
- BAF312, Placebo
- First posted
- 2012-08-15
- Last updated
- 2024-06-05
- Other registries' IDs
- eudract:2012-003056-36
- Results first posted
- 2018-10-31
Source ClinicalTrials.gov
Registered outcomes14
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | Baseline, every 3 month up to the maximum of approximately 3 years | The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). 3-month confirmed disability progression is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5 sustained for at least 3 months. |
| Secondary | Percentage of Participants With 3-month Confirmed Worsening in T25W of at Least 20% From Baseline | Baseline, every 3 months up to the maximum of approximately 3 years | The Timed 25-Foot Walk Test (T25W) measured the time, in seconds, to walk 25 feet (7.62 meters). A 3-month confirmed worsening of at least 20% from baseline in the T25W was defined as an increase from baseline sustained for at least 3 months. This outcome measure was analyzed using a Cox proportional hazards model. |
| Secondary | Change From Baseline in T2 Lesion Volume | Baseline, Month 12 and Month 24 | Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the total volume of T2 lesions. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center. The change from baseline in T2 lesion volume was analyzed using a mixed model for repeated measures (MMRM) with visit as a categorical factor and an unstructured covariance matrix and with adjustment for baseline covariates. |
| Secondary | Percentage of Participants With 6-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | Baseline, every 3 months up to the maximum of approximately 3 years | The EDSS uses an ordinal scale to assess neurologic impairment in multiple sclerosis (MS) based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). 6-month confirmed disability progression is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5 sustained for at least 6 months. This outcome measure was analyzed using a Cox proportional hazards model. |
| Secondary | Annualized Relapse Rate (ARR) for Confirmed Relapses | Up to maximum approximately 3 years | Multiple sclerosis (MS) relapse was defined as appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. Additionally, the abnormality had to be present for at least 24 hours and occur in the absence of fever (\<37.5°C) or known infection. A confirmed MS relapse was defined as accompanied by a clinically-relevant change in the EDSS, as defined in the study protocol, performed by the Independent EDSS Rater. ARR was defined as the average number of confirmed relapses per year. ARR was analyzed using a negative binomial regression model. |
| Secondary | Percentage of Participants With First Relapse Events as Measured by Time to First Confirmed Relapse | Up to maximum approximately 3 years | Multiple sclerosis (MS) relapse was defined as appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. Additionally, the abnormality had to be present for at least 24 hours and occur in the absence of fever (\<37.5°C) or known infection. A confirmed MS relapse was defined as accompanied by a clinically-relevant change in the EDSS, as defined in the study protocol, performed by the Independent EDSS Rater. Time to first relapse was defined as the time from Day 1 until the start of relapse symptoms. Patients without relapse were censored at the latest known date to be at risk. This outcome measure was analyzed using a Cox proportional hazards model. |
| Secondary | Percentage of Patients With Relapse (Confirmed Relapse and Any Relapse) | Up to maximum approximately 3 years | Multiple sclerosis (MS) relapse was defined as appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. Additionally, the abnormality had to be present for at least 24 hours and occur in the absence of fever (\<37.5°C) or known infection. A confirmed MS relapse was defined as accompanied by a clinically-relevant change in the EDSS, as defined in the study protocol, performed by the Independent EDSS Rater. |
| Secondary | Change From Baseline in MSWS-12 Converted Score | Baseline, Month 12 and Month 24 | The Multiple Sclerosis Walking Scale (MSWS-12) version 2 is a patient-rated measure of walking consisting of 12 items. Walking limitations were reported by the patients using categories, generating a total transformed score ranging from 0-100. Higher scores reflected greater impairment. The change from baseline in MSWS-12 converted score was analyzed using a repeated measures model. |
| Secondary | Number of T1 Gd-enhancing Lesions Per Patient Per Scan | Baseline, Month 12 and Month 24 | Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the number of T1 gadolinium (Gd)-enhancing lesions. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center. The number of T1 Gd-enhancing lesions per patient per scan was analyzed using a negative binomial regression model. |
| Secondary | Number of New or Enlarging T2 Lesions Per Patient Per Year | Baseline, Month 12 and Month 24 | Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the number of new or enlarging T2 lesions. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center. The number of new or enlarging T2 lesions compared to previous scan was analyzed using a repeated measures negative binomial regression model. |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 registered outcomesOutcomes14
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | Baseline, every 3 month up to the maximum of approximately 3 years | The Full analysis set (FAS), which comprised all randomized patients with assigned treatments who took at least one dose of study medication, was considered for the analysis. Only participants from the FAS with non-missing covariates were analyzed for this outcome. | Percentage of participants | NUMBER |
| SECONDARY | Percentage of Participants With 3-month Confirmed Worsening in T25W of at Least 20% From Baseline | Baseline, every 3 months up to the maximum of approximately 3 years | Participants from the FAS with non-missing covariates for the model. | Percentage of participants | NUMBER |
| SECONDARY | Change From Baseline in T2 Lesion Volume | Baseline, Month 12 and Month 24 | Participants from the FAS with at least one post-baseline MRI scan and non-missing covariates for the model. | mm^3 | LEAST_SQUARES_MEAN |
| SECONDARY | Percentage of Participants With 6-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | Baseline, every 3 months up to the maximum of approximately 3 years | Participants from the FAS with non-missing covariates for the model. | Percentage of participants | NUMBER |
| SECONDARY | Annualized Relapse Rate (ARR) for Confirmed Relapses | Up to maximum approximately 3 years | All participants in the FAS | relapses/year | MEAN |
| SECONDARY | Percentage of Participants With First Relapse Events as Measured by Time to First Confirmed Relapse | Up to maximum approximately 3 years | Participants from the FAS with non-missing covariates for the model. | Percentage of participants | NUMBER |
| SECONDARY | Percentage of Patients With Relapse (Confirmed Relapse and Any Relapse) | Up to maximum approximately 3 years | All participants in the FAS | Percentage of participants | NUMBER |
| SECONDARY | Change From Baseline in MSWS-12 Converted Score | Baseline, Month 12 and Month 24 | Participants from the FAS with an available value for the MSWS-12 converted score at baseline and at least one post-baseline. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Number of T1 Gd-enhancing Lesions Per Patient Per Scan | Baseline, Month 12 and Month 24 | Participants from the FAS with at least one post-baseline MRI scan and non-missing values for the covariates included in the model. | T1 Gd-enhancing lesions/patient/scan | LEAST_SQUARES_MEAN |
| SECONDARY | Number of New or Enlarging T2 Lesions Per Patient Per Year | Baseline, Month 12 and Month 24 | Participants from the FAS with at least one post-baseline MRI scan and non-missing values for the covariates included in the model. | T2 lesions/patient/year | LEAST_SQUARES_MEAN |
1 to 10 of 14Source ClinicalTrials.gov
See all 14 outcomesResults by group52
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | Siponimod (BAF312) | 26.3 | Percentage of participants | ||
| Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | Placebo | 31.7 | Percentage of participants | ||
| Percentage of Participants With 3-month Confirmed Worsening in T25W of at Least 20% From Baseline | Siponimod (BAF312) | 39.7 | Percentage of participants | ||
| Percentage of Participants With 3-month Confirmed Worsening in T25W of at Least 20% From Baseline | Placebo | 41.4 | Percentage of participants | ||
| Change From Baseline in T2 Lesion Volume | Siponimod (BAF312) | Month 12 | 204.9 | Standard Error 67.47 | mm^3 |
| Change From Baseline in T2 Lesion Volume | Placebo | Month 12 | 818.0 | Standard Error 87.29 | mm^3 |
| Change From Baseline in T2 Lesion Volume | Siponimod (BAF312) | Month 24 | 162.9 | Standard Error 73.90 | mm^3 |
| Change From Baseline in T2 Lesion Volume | Placebo | Month 24 | 940.4 | Standard Error 97.20 | mm^3 |
| Change From Baseline in T2 Lesion Volume | Siponimod (BAF312) | Average over Month 12 and Month 24 | 183.9 | Standard Error 66.33 | mm^3 |
| Change From Baseline in T2 Lesion Volume | Placebo | Average over Month 12 and Month 24 | 879.2 | Standard Error 85.43 | mm^3 |
1 to 10 of 52Source ClinicalTrials.gov
See all 52 results by groupParticipant flow24
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Core Part | STARTED | Siponimod (BAF312) | 1,105 | |
| Core Part | STARTED | Placebo | 546 | |
| Core Part | STARTED | Placebo-BAF312 | 0 | |
| Core Part | Safety Set | Siponimod (BAF312) | 1,099 | |
| Core Part | Safety Set | Placebo | 546 | |
| Core Part | Safety Set | Placebo-BAF312 | 0 | |
| Core Part | Full Analysis Set | Siponimod (BAF312) | 1,099 | |
| Core Part | Full Analysis Set | Placebo | 546 | |
| Core Part | Full Analysis Set | Placebo-BAF312 | 0 | |
| Core Part | COMPLETED | Siponimod (BAF312) | 903 |
1 to 10 of 24Source ClinicalTrials.gov
See all 24 participant flowAdverse events1,608
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Lymphopenia | Blood and lymphatic system disorders | Core-BAF312 | 9 | 1,099 | |
| other | Lymphopenia | Blood and lymphatic system disorders | Core-Placebo | 0 | 546 | |
| other | Lymphopenia | Blood and lymphatic system disorders | All BAF312 | 137 | 1,517 | |
| other | Constipation | Gastrointestinal disorders | Core-BAF312 | 39 | 1,099 | |
| other | Constipation | Gastrointestinal disorders | Core-Placebo | 21 | 546 | |
| other | Constipation | Gastrointestinal disorders | All BAF312 | 103 | 1,517 | |
| other | Diarrhoea | Gastrointestinal disorders | Core-BAF312 | 69 | 1,099 | |
| other | Diarrhoea | Gastrointestinal disorders | Core-Placebo | 22 | 546 | |
| other | Diarrhoea | Gastrointestinal disorders | All BAF312 | 119 | 1,517 | |
| other | Nausea | Gastrointestinal disorders | Core-BAF312 | 73 | 1,099 |
1 to 10 of 1,608Source ClinicalTrials.gov
See all 1,608 adverse eventsAdverse event totals9
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Core-BAF312 | 4 | 1,099 |
| Total, all-cause mortality | Core-Placebo | 4 | 546 |
| Total, all-cause mortality | All BAF312 | 33 | 1,517 |
| Total, other adverse events | Core-BAF312 | 778 | 1,099 |
| Total, other adverse events | Core-Placebo | 348 | 546 |
| Total, other adverse events | All BAF312 | 1,267 | 1,517 |
| Total, serious adverse events | Core-BAF312 | 196 | 1,099 |
| Total, serious adverse events | Core-Placebo | 83 | 546 |
| Total, serious adverse events | All BAF312 | 610 | 1,517 |
Source ClinicalTrials.gov
Papers7
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
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