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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01665144
First received: August 3, 2012
Last updated: May 9, 2016
Last verified: May 2016
  Purpose
Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis (Core Part) followed by extended treatment with open-label BAF312 to obtain data on long-term safety, tolerabiilty and efficacy (Extension Part).

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 Followed by Extended Treatment With Open-label BAF312.

Resource links provided by NLM:


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 approximately 3 years ] [ 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 approximately 3 years ] [ 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 approximately 3 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 approximately 3 years ] [ 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 approximately 3 years ] [ 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 approximately 3 years ] [ 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 approximately 3 years ] [ 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 approximately 3 years ] [ 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 events during the Core Part [ Time Frame: Baseline, every 3 months up to the maximum of approximately 3 years ] [ 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 during the Core Part [ Time Frame: Baseline, every 3 months up to the maximum of approximately 3 years ] [ Designated as safety issue: Yes ]
    Safety analysis will be performed on lab abnormalities will be based on CTCAE grades

  • Number of patients with adverse events during the Extension Part [ Time Frame: Following the Core Part of the study, every 3 months for one year and then every 6 months up to the maximum of 84 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 during the Extension Part [ Time Frame: Following the Core Part of the study, every 3 months for the first year and then every 6 months up to the maximum of 84 months ] [ Designated as safety issue: Yes ]
    Safety analysis will be performed on lab abnormalities will be based on CTCAE grades


Enrollment: 1649
Study Start Date: December 2012
Estimated Study Completion Date: August 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAF312
1090 patients will be randomized to receive BAF312 during the trial for a maximum of approximately 3 years (Core Part). Patients who meet all inclusion and none of the exclusion criteria will be treated with BAF312 daily. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312 for a maximum of 84 additional months.
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 during the Core Part of the trial. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312 for a maximum of 84 additional months.
Drug: Placebo
Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years   (Adult)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

  Show 315 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01665144     History of Changes
Other Study ID Numbers: CBAF312A2304 
Study First Received: August 3, 2012
Last Updated: May 9, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Secondary Progressive Multiple Sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Neoplasm Metastasis
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Neoplastic Processes
Neoplasms

ClinicalTrials.gov processed this record on July 24, 2016