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

Secondary Progressive Multiple Sclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02330965
• Other study ID #: DAIT AMS04
• Status: Completed
• Start date: December 2014
• Est. completion date: July 12, 2017

Study information

• Verified date: November 2020
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 12, 2017
• Est. primary completion date: July 12, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of New Mexico: Health Sciences Center	Albuquerque	New Mexico
United States	University of Michigan Health System -Multiple Sclerosis Center	Ann Arbor	Michigan
United States	University of Colorado	Aurora	Colorado
United States	Jordan Research & Education Institute: Sutter Alta Bates Summit	Berkeley	California
United States	Carolinas Medical Center (CMC)	Charlotte	North Carolina
United States	Cleveland Clinic: Mellen Center for Multiple Sclerosis	Cleveland	Ohio
United States	Henry Ford Health System	Detroit	Michigan
United States	Minneapolis Clinic of Neurology	Golden Valley	Minnesota
United States	University of Southern California	Los Angeles	California
United States	South Shore Neurologic Associates - Multiple Sclerosis Care Center	Patchogue	New York
United States	Providence Multiple Sclerosis Center	Portland	Oregon
United States	University of California, Davis	Sacramento	California
United States	Swedish Neuroscience Institute	Seattle	Washington

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Autoimmunity Centers of Excellence, Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & 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). pii: 134251. doi: 10.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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).
Secondary	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).
Secondary	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).
Secondary	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).

External Links

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