Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND) - Full Text View

Purpose

Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis.

Condition	Intervention	Phase
Secondary Progressive Multiple Sclerosis	Drug: BAF312 Drug: Placebo	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis.

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

The delay in time to confirmed disability progression as measured by EDSS. [ Time Frame: Baseline, every 3 month up to the maximum of 60 months ] [ Designated as safety issue: No ]
Confirmed disability is defined as an Increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.

Secondary Outcome Measures:

Efficacy of BAF312 relative to placebo in confirmed worsening of 25 foot walk test [ Time Frame: Baseline , every 3 months up to the maximum of 60 months ] [ Designated as safety issue: No ]
Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test.
Efficacy of BAF312 relative to placebo in reducing the increase in T2 lesion volume [ Time Frame: Baseline, every year up to the maximum of 5 years ] [ Designated as safety issue: No ]
The reduction of the increase in the T1 lesion volume.
The delay in time to confirmed disability progression as measured by EDSS. [ Time Frame: Baseline, every 6 months up to the maximum of 60 months ] [ Designated as safety issue: No ]
Confirmed disability is defined as increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.
Efficacy of BAF relative to placebo in annualized relapses rate and time to the first relapse [ Time Frame: Baseline every 3 months up to the maximum of 60 months ] [ Designated as safety issue: No ]
BAF312 vs placebo measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.
Overall response rate on the MSWS-12. [ Time Frame: Baseline, every 6 months up to the maximum of 60 months ] [ Designated as safety issue: No ]
The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12.
Effect on inflammatory disease activity and burden of disease as measured by MRI [ Time Frame: Baseline, every 12 month up to the maximum of 60 months ] [ Designated as safety issue: No ]
Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans.
effect on 3-month confirmed disability progression as defined by EDSS in predefined sub-groups [ Time Frame: Baseline, every 3 months up to the maximum of 60 months ] [ Designated as safety issue: No ]
effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria.
Number of patients with adverse event [ Time Frame: Baseline, every 3 months up to the maximum of 60 months ] [ Designated as safety issue: Yes ]
Safety analysis will be performed on AE by CTCAE grade, serious AEs and Study drug related AEs and the AEs leading to discontinuation of study drug.
Number of patients with abnormal lab tests [ Time Frame: Baseline, every 3 months up to the maximum of 60 months ] [ Designated as safety issue: Yes ]
Safety analysis will be performed on lab abnormalities will be based on CTCAE grades

Estimated Enrollment:	1530
Study Start Date:	January 2012
Estimated Study Completion Date:	September 2016
Estimated Primary Completion Date:	September 2016 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: BAF312 1020 patients will be randomized to receive BAF312 during the trial for a duration of 23 to 42 months with a maximum of 60 months. Patients who meet all inclusion and none of the exclusion criteria will be treated with BAF312 daily.	Drug: BAF312 Patients will be randomized to receive BAF312. BAF312 will be provided in a dose titration from 0.25 mg to a 2 mg dose.
Placebo Comparator: Placebo Matching Placebo administered orally.	Drug: Placebo Placebo

Eligibility

Ages Eligible for Study:	18 Years to 60 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Prior history of relapsing remitting MS
SPMS defined as progressive increase of disability over at least 6 months
EDSS score of 3.0 to 6.5
No relapse of corticosteroid treatment within 3 months

Exclusion Criteria:

Women of child bearing potential must use reliable forms of contraception.
Diagnosis of Macular edema during screening period
Any medically unstable condition determined by investigator.
Unable to undergo MRI scans
Hypersensitivity to any study drugs or drugs of similar class Other protocol defined inclusion/exclusion may apply.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01665144

Contacts

Contact: Novartis Pharmaceuticals	1-888-669-6682
Contact: Novartis Pharmaceuticals

Show 292 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:	NCT01665144 History of Changes
Other Study ID Numbers:	CBAF312A2304
Study First Received:	August 3, 2012
Last Updated:	February 12, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Secondary Progressive Multiple Sclerosis

Additional relevant MeSH terms:

Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Chronic Progressive
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System

Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on May 16, 2013