Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)

Study Overview
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Brief Summary
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Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis (Core Part) followed by extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability and efficacy (Extension Part).

Official Title
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A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.

Conditions
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Secondary Progressive Multiple Sclerosis

Intervention / Treatment
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* Drug: BAF312
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior history of relapsing remitting MS SPMS defined as progressive increase of disability over at least 6 months EDSS score of 3.0 to 6.5 No relapse of corticosteroid treatment within 3 months Exclusion Criteria: Women of child bearing potential must use reliable forms of contraception. Diagnosis of Macular edema during screening period Any medically unstable condition determined by investigator. Unable to undergo MRI scans Hypersensitivity to any study drugs or drugs of similar class Other protocol defined inclusion/exclusion may apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Siponimod (BAF312)<br>Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312. | Drug: BAF312<br>* 0.25, 0.5, 1, and 2 mg film-coated tablets<br>|
| Placebo Comparator: Placebo<br>Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312. | Drug: Placebo<br>* Film-coated tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) | 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). Confirmed disability 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. | Baseline, every 3 month up to the maximum of approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of BAF312 Relative to Placebo in Confirmed Worsening of 25 Foot Walk Test | Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test. | Baseline , every 3 months up to the maximum of approximately 3 years | 
| Efficacy of BAF312 Relative to Placebo in Reducing the Increase in T2 Lesion Volume | Efficacy is shown by the reduction of the increase in T1 lesion volume. | Baseline, every year up to the maximum of approximately 3 years | 
| The Delay in Time to Confirmed Disability Progression as Measured by EDSS. | Confirmed disability is defined as 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. | Baseline, every 6 months up to the maximum of approximately 3 years | 
| Efficacy of BAF Relative to Placebo in Annualized Relapses Rate and Time to the First Relapse | Efficacy of BAF312 relative to placebo was measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses. | Baseline every 3 months up to the maximum of approximately 3 years | 
| Overall Response Rate on the MSWS-12. | The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12. | Baseline, every 6 months up to the maximum of approximately 3 years | 
| Effect on Inflammatory Disease Activity and Burden of Disease as Measured by MRI | Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans. | Baseline, every 12 month up to the maximum of approximately 3 years | 
| Effect on 3-month Confirmed Disability Progression as Defined by EDSS in Predefined Sub-groups | effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria. | Baseline, every 3 months up to the maximum of approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Secondary Progressive Multiple Sclerosis