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

NCT02330965 | Completed

• 1 other identifier: DAIT AMS04
• Study Type: observational
• Target: 36
• Locations: 1 country
• Sites: 13

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.

Conditions

Secondary Progressive Multiple Sclerosis

Keywords

autoimmunity; clinical research; mechanistic studies; blood draw; cerebrospinal fluid (CSF) by lumbar puncture (optional)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• 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).

• Change in chemokine and cytokines levels

  From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).

• Change in Regulatory B Cells

  From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).

• Changes of clinical status and lymphocyte subgroups

  From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).

Study Arms (2)

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.

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

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.

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

Interventions

Blood Draw PROCEDURE

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.

Also known as: Phlebotomy, Venipuncture

Subjects Assigned to BAF312; Subjects Assigned to Placebo (Controls)

CSF collection by lumbar puncture (Optional) PROCEDURE

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.

Also known as: CSF by LP, cerebrospinal fluid collected by lumbar puncture

Subjects Assigned to BAF312; Subjects Assigned to Placebo (Controls)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Ambulatory participants with Secondary Progressive Multiple Sclerosis (SPMS) enrolled in the EXPAND trial (BAF312 treated and placebo \[control\] participants) may be enrolled in this study after the EXPAND baseline visit has occurred provided that the subject has not passed the Month 12 time point. -Refer to ClinicalTrials.gov record NCT01665144.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Autoimmunity Centers of Excellence: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (13)

Jordan Research & Education Institute: Sutter Alta Bates Summit

Berkeley, California, 94705, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

University of Michigan Health System -Multiple Sclerosis Center

Ann Arbor, Michigan, 48109, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, 55422, United States

Location

University of New Mexico: Health Sciences Center

Albuquerque, New Mexico, 87131, United States

Location

South Shore Neurologic Associates - Multiple Sclerosis Care Center

Patchogue, New York, 11772, United States

Location

Carolinas Medical Center (CMC)

Charlotte, North Carolina, 28207, United States

Location

Cleveland Clinic: Mellen Center for Multiple Sclerosis

Cleveland, Ohio, 44195, United States

Location

Providence Multiple Sclerosis Center

Portland, Oregon, 97225, United States

Location

Swedish Neuroscience Institute

Seattle, Washington, 98122, United States

Location

Related Publications (1)

• 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.

  PMID: 31935197 RESULT

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Division of Allergy, Immunology, and Transplantation (DAIT)
• Relevant Clinical Trials.gov Record: NCT01665144

Biospecimen

Retention: SAMPLES WITH DNA

Blood \& Cerebrospinal Fluid Samples

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Autoimmune Diseases

Interventions

Blood Specimen Collection; Phlebotomy

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Therapeutics

Study Officials

• Yang Mao-Draayer, MD, PhD

  Multiple Sclerosis Center - University of Michigan Health System

  STUDY CHAIR

• David Fox, MD

  Division of Rheumatology - University of Michigan Health System

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 31, 2014
• First Posted: January 5, 2015
• Study Start: December 1, 2014
• Primary Completion: July 12, 2017
• Study Completion: July 12, 2017
• Last Updated: November 9, 2020

Record last verified: 2020-11

Locations

US (13)