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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT02330965
• Collaborator: Autoimmunity Centers of Excellence (Other), Novartis Pharmaceuticals (Industry)
• Enrollment: 36
• Locations: 13
• Duration (Months): 31.3
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Secondary Progressive Multiple Sclerosis	Procedure: Blood Draw; Procedure: CSF collection by lumbar puncture (Optional)

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 Design

• Study Type: Observational
• Actual Enrollment: 36 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)
• Study Start Date: Dec 1, 2014
• Actual Primary Completion Date: Jul 12, 2017
• Actual Study Completion Date: Jul 12, 2017

Arms and Interventions

Arm	Intervention/Treatment
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; 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.; Other Names: Phlebotomy Venipuncture ; 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.; Other Names: CSF by LP cerebrospinal fluid collected by lumbar puncture
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; 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.; Other Names: Phlebotomy Venipuncture ; 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.; Other Names: CSF by LP cerebrospinal fluid collected by lumbar puncture

Outcome Measures

Primary Outcome Measures

1. 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

1. 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

2. 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

3. 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

4. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jordan Research & Education Institute: Sutter Alta Bates Summit	Berkeley	California	United States	94705
2	University of Southern California	Los Angeles	California	United States	90033
3	University of California, Davis	Sacramento	California	United States	95817
4	University of Colorado	Aurora	Colorado	United States	80045
5	University of Michigan Health System -Multiple Sclerosis Center	Ann Arbor	Michigan	United States	48109
6	Henry Ford Health System	Detroit	Michigan	United States	48202
7	Minneapolis Clinic of Neurology	Golden Valley	Minnesota	United States	55422
8	University of New Mexico: Health Sciences Center	Albuquerque	New Mexico	United States	87131
9	South Shore Neurologic Associates - Multiple Sclerosis Care Center	Patchogue	New York	United States	11772
10	Carolinas Medical Center (CMC)	Charlotte	North Carolina	United States	28207
11	Cleveland Clinic: Mellen Center for Multiple Sclerosis	Cleveland	Ohio	United States	44195
12	Providence Multiple Sclerosis Center	Portland	Oregon	United States	97225
13	Swedish Neuroscience Institute	Seattle	Washington	United States	98122

Sponsors and Collaborators

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

Investigators

• Study Chair: 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 Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT02330965
• Other Study ID Numbers: DAIT AMS04
• First Posted: Jan 5, 2015
• Last Update Posted: Nov 9, 2020
• Last Verified: Nov 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): autoimmunity; clinical research; mechanistic studies; blood draw; cerebrospinal fluid (CSF) by lumbar puncture (optional)
• Additional relevant MeSH terms: Neoplasm Metastasis; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis

Study Results

No Results Posted as of Nov 9, 2020