Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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The primary goal of this study is to evaluate the effects of BAF312 (siponimod) on select immune and neuronal (nerve) cells by examining laboratory specimens (blood and/or spinal fluid) at multiple time points, prior to, and following the initiation of BAF312 or placebo treatment, in patients with Secondary Progressive Multiple Sclerosis (SPMS) who are enrolled in a clinical trial (NCT01665144) to evaluate the effectiveness and safety of BAF312.

Detailed Description
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This study is complementary to a multi-center, randomized, double-blind,parallel-group, placebo-controlled, variable treatment duration study comparing the efficacy and safety of BAF312 to placebo in patients with SPMS (NCT01665144). Investigators will explore both immunological and neuroprotective mechanisms of BAF312 (siponimod), a novel agent in the setting of a SPMS clinical trial. This study is part of a multi-center study, with the University of Michigan serving as the central site.

Official Title
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Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)

Conditions
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Secondary Progressive Multiple Sclerosis

Intervention / Treatment
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* Procedure: Blood Draw
* Procedure: CSF collection by lumbar puncture (Optional)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants enrolled in the multicenter, randomized, double-blind, parallel-group, placebo-controlled, variable treatment duration study comparing the efficacy and safety of BAF312 to placebo in patients with Secondary Progressive Multiple Sclerosis (SPMS) Protocol No. CBAF312A2304 (sponsored by Novartis). Refer to ClinicalTrials.gov record NCT01665144. Subjects enrolled at one of the participating AMS04 study sites located in the United States. Subject must be able to provide written informed consent. Exclusion Criteria: Subjects with severe bleeding disorders, platelet count less than (<)50,000/microliters (μL), and/or who are currently on full anticoagulant therapy will be excluded from the optional CSF collections.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Subjects Assigned to BAF312<br>Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive BAF312 (siponimod). Refer to ClinicalTrials.gov record NCT01665144 for more information. | Procedure: Blood Draw<br>* Blood draws (65 mLs [ 4 tablespoons] per blood draw) at 4 time points: Prior to study medication initiation, and at +6, +12 and+24 months post treatment initiation.<br>* Other names: Venipuncture;Procedure: CSF collection by lumbar puncture (Optional)<br>* For participants who volunteer to donate CSF samples: up to 25 mLs (<2 tablespoons): prior to study medication initiation, and at month 24 post treatment initiation.<br>* Other names: cerebrospinal fluid collected by lumbar puncture;|
| Subjects Assigned to Placebo (Controls)<br>Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive placebo. Refer to ClinicalTrials.gov record NCT01665144 for more information. | Procedure: Blood Draw<br>* Blood draws (65 mLs [ 4 tablespoons] per blood draw) at 4 time points: Prior to study medication initiation, and at +6, +12 and+24 months post treatment initiation.<br>* Other names: Venipuncture;Procedure: CSF collection by lumbar puncture (Optional)<br>* For participants who volunteer to donate CSF samples: up to 25 mLs (<2 tablespoons): prior to study medication initiation, and at month 24 post treatment initiation.<br>* Other names: cerebrospinal fluid collected by lumbar puncture;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in frequency of MBP-reactive Th17 cells | Evaluation (BAF312 versus placebo) of dominant cytokines produced by myelin basic protein (MBP)-stimulated peripheral blood mononuclear cells (PBMCs), measured by ELISpot. | From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in frequency of polyclonal CD4+ Th17, Th1, Th2, and Treg cells | Compare BAF312 and Placebo (Control) Groups | From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months). | 
| Change in chemokine and cytokines levels | Compare BAF312 and Placebo (Control) Groups | From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months). | 
| Change in Regulatory B Cells | Compare BAF312 and Placebo (Control) Groups | From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months). | 
| Changes of clinical status and lymphocyte subgroups | Compare BAF312 and Placebo (Control) Groups | From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autoimmunity, clinical research, mechanistic studies, blood draw, cerebrospinal fluid (CSF) by lumbar puncture (optional)