Secondary Progressive Multiple SclerosisNCT02330965
Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis
An observational study of Secondary Progressive Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Secondary Progressive Multiple Sclerosis
- What is being tested?
- Blood Draw and CSF collection by lumbar puncture (Optional)
- Type of treatment
- Surgery or procedure
- How many people
- 36 participants
- Where
- 13 sitesUnited States
- Study dates
- Dec 2014to 12 Jul 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
University of New Mexico: Health Sciences Center
Albuquerque, New Mexico, 87131
University of Michigan Health System -Multiple Sclerosis Center
Ann Arbor, Michigan, 48109
University of Colorado
Aurora, Colorado, 80045
Jordan Research & Education Institute: Sutter Alta Bates Summit
Berkeley, California, 94705
Carolinas Medical Center (CMC)
Charlotte, North Carolina, 28207
Cleveland Clinic: Mellen Center for Multiple Sclerosis
Cleveland, Ohio, 44195
Henry Ford Health System
Detroit, Michigan, 48202
Minneapolis Clinic of Neurology
Golden Valley, Minnesota, 55422
University of Southern California
Los Angeles, California, 90033
South Shore Neurologic Associates - Multiple Sclerosis Care Center
Patchogue, New York, 11772
Providence Multiple Sclerosis Center
Portland, Oregon, 97225
University of California, Davis
Sacramento, California, 95817
Swedish Neuroscience Institute
Seattle, Washington, 98122
About this study
Official title: Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)
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.
Read the 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.
- Conditions
- Secondary Progressive Multiple Sclerosis
- Being tested
- Blood Draw, CSF collection by lumbar puncture (Optional)
- Keywords
- autoimmunity, clinical research, mechanistic studies, blood draw, cerebrospinal fluid (CSF) by lumbar puncture (optional)
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive, Autoimmune Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood DrawProcedure or surgery
Also called Phlebotomy, Venipuncture
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)Procedure or surgery
Also called CSF by LP, cerebrospinal fluid collected by lumbar puncture
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Blood Draw; Procedure: CSF collection by lumbar puncture (Optional) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Compare BAF312 and Placebo (Control) Groups
Measured: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Change in chemokine and cytokines levels
Compare BAF312 and Placebo (Control) Groups
Measured: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Change in Regulatory B Cells
Compare BAF312 and Placebo (Control) Groups
Measured: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Changes of clinical status and lymphocyte subgroups
Compare BAF312 and Placebo (Control) Groups
Measured: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jan 2015 (estimated)
- Study startDec 2014
- Primary completion12 Jul 2017
- Study completion12 Jul 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Secondary Progressive Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence, Novartis Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Yang Mao-Draayer, MD, PhD, Study chair, Multiple Sclerosis Center - University of Michigan Health SystemDavid Fox, MD, Study chair, Division of Rheumatology - University of Michigan Health System
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02330965
- Sponsor's protocol ID
- DAIT AMS04
- Status last verified
- Nov 2020
- First submitted
- 31 Dec 2014
- Last updated
- 9 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 31935197
Study at a glance
From the registry record, last updated by the sponsor on 9 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Studies of Phase III Trial With BAF312 in Secondary Progressive Multiple Sclerosis (AMS04)
- ClinicalTrials.gov ID
- NCT02330965
- Acronym / sponsor ID
- DAIT AMS04
- Conditions
- Secondary Progressive Multiple Sclerosis
- Keywords
- autoimmunity, clinical research, mechanistic studies, blood draw, cerebrospinal fluid (CSF) by lumbar puncture (optional)
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Collaborators
- Autoimmunity Centers of Excellence, Novartis Pharmaceuticals
- Study start
- Dec 2014
- Primary completion
- 12 Jul 2017 (actual)
- Study completion
- 12 Jul 2017 (actual)
- First posted
- 5 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Subjects Assigned to BAF312 | – | Procedure: Blood Draw, Procedure: 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 Placebo (Controls) | – | Procedure: Blood Draw, Procedure: 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- 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.
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood DrawAlso: Phlebotomy, VenipunctureBlood 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. | Procedure or surgery | Subjects Assigned to BAF312, Subjects Assigned to Placebo (Controls) |
| CSF collection by lumbar puncture (Optional)Also: CSF by LP, cerebrospinal fluid collected by lumbar punctureFor 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. | Procedure or surgery | Subjects Assigned to BAF312, Subjects Assigned to Placebo (Controls) |
Primary outcome
Change in frequency of MBP-reactive Th17 cells
Time frame: 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.
4 secondary outcomes
Change in frequency of polyclonal CD4+ Th17, Th1, Th2, and Treg cells
Time frame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Change in chemokine and cytokines levels
Time frame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Change in Regulatory B Cells
Time frame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Changes of clinical status and lymphocyte subgroups
Time frame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Nov 2020.
- Results publication: PubMed 31935197Wu 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.
- National Institute of Allergy and Infectious Diseases (NIAID)Link provided by the sponsor.
- Division of Allergy, Immunology, and Transplantation (DAIT)Link provided by the sponsor.
- Relevant Clinical Trials.gov Record: NCT01665144Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yang Mao-Draayer, MD, PhD study chair
Multiple Sclerosis Center - University of Michigan Health System
David Fox, MD study chair
Division of Rheumatology - University of Michigan Health System
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Secondary Progressive Multiple Sclerosis, run by National Institute of Allergy and Infectious Diseases (NIAID) at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in frequency of MBP-reactive Th17 cells (time frame: From baseline to the follow-up time points (Open label phase + 6 months and OLP +12 months).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02330965, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Nov 2020.