Clinical trial NCT02330965: Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis
Official title: Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Secondary Progressive Multiple Sclerosis
Keywords: autoimmunity
clinical research
mechanistic studies
blood draw
cerebrospinal fluid (CSF) by lumbar puncture (optional)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Autoimmunity Centers of Excellence
name: Novartis Pharmaceuticals
First posted: 2015-01-05
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in frequency of MBP-reactive Th17 cells
timeFrame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Secondary outcomes:
measure: Change in frequency of polyclonal CD4+ Th17, Th1, Th2, and Treg cells
timeFrame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
measure: Change in chemokine and cytokines levels
timeFrame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
measure: Change in Regulatory B Cells
timeFrame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
measure: Changes of clinical status and lymphocyte subgroups
timeFrame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Jordan Research & Education Institute: Sutter Alta Bates Summit
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Sacramento
country: United States
facility: University of California, Davis
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Ann Arbor
country: United States
facility: University of Michigan Health System -Multiple Sclerosis Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Albuquerque
country: United States
facility: University of New Mexico: Health Sciences Center
state: New Mexico
city: Patchogue
country: United States
facility: South Shore Neurologic Associates - Multiple Sclerosis Care Center
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center (CMC)
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic: Mellen Center for Multiple Sclerosis
state: Ohio
city: Portland
country: United States
facility: Providence Multiple Sclerosis Center
state: Oregon
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
Study officials:
affiliation: Multiple Sclerosis Center - University of Michigan Health System
name: Yang Mao-Draayer, MD, PhD
role: STUDY_CHAIR
affiliation: Division of Rheumatology - University of Michigan Health System
name: David Fox, MD
role: STUDY_CHAIR
References:
citation: 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.