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Trial record 1 of 1 for:    CBAF312A2304
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Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)

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ClinicalTrials.gov Identifier: NCT01665144
Recruitment Status : Active, not recruiting
First Posted : August 15, 2012
Results First Posted : October 31, 2018
Last Update Posted : September 9, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE August 3, 2012
First Posted Date  ICMJE August 15, 2012
Results First Submitted Date  ICMJE August 6, 2018
Results First Posted Date  ICMJE October 31, 2018
Last Update Posted Date September 9, 2019
Actual Study Start Date  ICMJE December 20, 2012
Actual Primary Completion Date April 29, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline, every 3 month up to the maximum of approximately 3 years ]
The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 14, 2012)
The delay in time to confirmed disability progression as measured by EDSS. [ Time Frame: up to the maximum of 60 months ]
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.
Change History Complete list of historical versions of study NCT01665144 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 4, 2018)
  • 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 ]
    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 ]
    Efficacy is shown by the reduction of the increase in 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 ]
    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 ]
    Efficacy of BAF312 relative to placebo was 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 ]
    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 ]
    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 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2012)
  • 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 ]
    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 voluime [ Time Frame: Baseline, every year up to the maximum of 5 years ]
    The reduction of the increase in the T1 lesion volumne.
  • 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 ]
    Confirmed disabilty 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 ]
    BAF312 vs placebo measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.
  • Ovearall response rate on the MSWS-12. [ Time Frame: Baseline, every 6 months up to the maximum of 60 months ]
    The overall reponse 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 ]
    Effect of BAF312 relative to placebo on disease activtiy 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 disabilty progression as defined by EDSS in predefined sub-groups [ Time Frame: Baseline, every 3 months up to the maximum of 60 months ]
    effect on confirmed disabilty progression in pre-defined subgroups, including patients with or without superimposed relaspes, 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 ]
    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 ]
    Safety analysis will be performed on lab abnormalities will be based on CTCAE grades
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)
Official Title  ICMJE 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.
Brief Summary 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, tolerability and efficacy (Extension Part).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Secondary Progressive Multiple Sclerosis
Intervention  ICMJE
  • Drug: BAF312
    0.25, 0.5, 1, and 2 mg film-coated tablets
  • Drug: Placebo
    Film-coated tablets
Study Arms  ICMJE
  • Experimental: Siponimod (BAF312)
    Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312.
    Intervention: Drug: BAF312
  • Placebo Comparator: Placebo
    Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312.
    Intervention: Drug: Placebo
Publications * Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, Vermersch P, Arnold DL, Arnould S, Scherz T, Wolf C, Wallström E, Dahlke F; EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018 Mar 31;391(10127):1263-1273. doi: 10.1016/S0140-6736(18)30475-6. Epub 2018 Mar 23. Erratum in: Lancet. 2018 Nov 17;392(10160):2170.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: September 15, 2017)
1652
Original Estimated Enrollment  ICMJE
 (submitted: August 14, 2012)
1530
Estimated Study Completion Date  ICMJE September 22, 2023
Actual Primary Completion Date April 29, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Austria,   Belgium,   Bulgaria,   Canada,   China,   Czechia,   Estonia,   France,   Germany,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Japan,   Latvia,   Lithuania,   Netherlands,   Poland,   Portugal,   Romania,   Russian Federation,   Slovakia,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Egypt
 
Administrative Information
NCT Number  ICMJE NCT01665144
Other Study ID Numbers  ICMJE CBAF312A2304
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Locations: central Contact Info Novartis.email@novartis.com

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP