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

Completed

• Conditions: Secondary Progressive Multiple Sclerosis
• Interventions: Procedure: Blood Draw; Procedure: CSF collection by lumbar puncture (Optional)

• Registration Number: NCT02330965
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-12
• Study First Submitted: 2014-12-31
• Study First Submitted QC: 2014-12-31
• Study First Posted: 2015-01-05
• Primary Completion: 2017-07-12
• Study Completion: 2017-07-12
• Status Verified: 2020-11
• Last Update Submitted: 2020-11-05
• Last Update Posted: 2020-11-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Subjects Assigned to Placebo (Controls)	Blood Draw	Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive placebo. Refer to ClinicalTrials.gov record NCT01665144 for more information.
Subjects Assigned to BAF312	CSF collection by lumbar puncture (Optional)	Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive BAF312 (siponimod). Refer to ClinicalTrials.gov record NCT01665144 for more information.
Subjects Assigned to BAF312	Blood Draw	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)	CSF collection by lumbar puncture (Optional)	Patients with secondary progressive multiple sclerosis (SPMS) randomized to receive placebo. Refer to ClinicalTrials.gov record NCT01665144 for more information.

Primary Outcome Measures

Name	Time	Method
Change in frequency of MBP-reactive Th17 cells	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 Outcome Measures

Name	Time	Method
Changes of clinical status and lymphocyte subgroups	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 frequency of polyclonal CD4+ Th17, Th1, Th2, and Treg cells	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	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	From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).	Compare BAF312 and Placebo (Control) Groups

Trial Locations

Locations (13)

University of Southern California; 🇺🇸 Los Angeles, California, United States

Minneapolis Clinic of Neurology; 🇺🇸 Golden Valley, Minnesota, United States

Carolinas Medical Center (CMC); 🇺🇸 Charlotte, North Carolina, United States

Jordan Research & Education Institute: Sutter Alta Bates Summit; 🇺🇸 Berkeley, California, United States

University of New Mexico: Health Sciences Center; 🇺🇸 Albuquerque, New Mexico, United States

Cleveland Clinic: Mellen Center for Multiple Sclerosis; 🇺🇸 Cleveland, Ohio, United States

University of Michigan Health System -Multiple Sclerosis Center; 🇺🇸 Ann Arbor, Michigan, United States

Henry Ford Health System; 🇺🇸 Detroit, Michigan, United States

University of California, Davis; 🇺🇸 Sacramento, California, United States

University of Colorado; 🇺🇸 Aurora, Colorado, United States

South Shore Neurologic Associates - Multiple Sclerosis Care Center; 🇺🇸 Patchogue, New York, United States

Providence Multiple Sclerosis Center; 🇺🇸 Portland, Oregon, United States

Swedish Neuroscience Institute; 🇺🇸 Seattle, Washington, United States