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

Overview

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.

Full Title of Study: “Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Prospective
  • Study Primary Completion Date: July 12, 2017

Detailed Description

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.

Interventions

  • Procedure: Blood Draw
    • 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.
  • Procedure: CSF collection by lumbar puncture (Optional)
    • 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.

Arms, Groups and Cohorts

  • Subjects Assigned to BAF312
    • Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive BAF312 (siponimod). Refer to ClinicalTrials.gov record NCT01665144 for more information.
  • Subjects Assigned to Placebo (Controls)
    • Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive placebo. Refer to ClinicalTrials.gov record NCT01665144 for more information.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 60 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Institute of Allergy and Infectious Diseases (NIAID)
  • Collaborator
    • Autoimmunity Centers of Excellence
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Yang Mao-Draayer, MD, PhD, Study Chair, Multiple Sclerosis Center – University of Michigan Health System
    • David Fox, MD, Study Chair, Division of Rheumatology – University of Michigan Health System

Citations Reporting on Results

Wu Q, Mills EA, Wang Q, Dowling CA, Fisher C, Kirch B, Lundy SK, Fox DA, Mao-Draayer Y; AMS04 Study Group. Siponimod enriches regulatory T and B lymphocytes in secondary progressive multiple sclerosis. JCI Insight. 2020 Feb 13;5(3):e134251. doi: 10.1172/jci.insight.134251.

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