MSFrontier

Cognition

A 18-month, Open-label, Rater-blinded, Randomized, Multi-center, Active-controlled, Parallel-group Pilot Study to Assess Efficacy and Safety of Fingolimod in Comparison to Interferon Beta 1b in Treating the Cognitive Symptoms Associated to Relapsing-remitting Multiple Sclerosis and to Assess Possible Relationship of These Effects to Regional Brain Atrophy
CompletedPhase 4Relapsing MSNCT013335012010-023023-19

What it found

Missed its main goal

The main measure did not show a significant benefit.

MeasureEstimate95% CIp
Change From Screening in Spatial Recall Test (SPART) Raw ScoreMean Difference (Net) -1.60-3.69–0.500.1334
Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2Mean Difference (Net) -5.24-12.62–2.140.1610
Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2Mean Difference (Net) -2.16-6.82–2.500.3585
Change From Screening in Symbol Digit Modalities Test (SDMT) Raw ScoreMean Difference (Net) -1.73-6.27–2.810.4501
Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw ScoreMean Difference (Net) 1.86-3.51–7.230.4940
Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw ScoreMean Difference (Net) 1.97-4.06–7.990.5183
Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2Mean Difference (Net) -0.25-1.42–0.920.6757
Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw ScoreMean Difference (Net) 0.17-0.76–1.110.7119
Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw ScoreMean Difference (Net) 0.46-4.57–5.490.8561
Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw ScoreMean Difference (Net) 0.37-4.67–5.400.8858
Change From Screening in Word List Generation (WLG)Mean Difference (Net) 0.16-2.18–2.500.8944
Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)Mean Difference (Net) -0.03-0.86–0.810.9496

Statistical analysis as posted on ClinicalTrials.gov.

What was tested

Treatment tested

Compared with

Results by group

Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod6.32 raw score1.33 (Standard Error)80
Interferon Beta 1b4.46 raw score2.28 (Standard Error)28

Fingolimod

6.32

Interferon Beta 1b

4.46

p = 0.4940; Mean Difference (Net) 1.86 (95% CI -3.51–7.23)

Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod5.93 Raw score1.49 (Standard Error)80
Interferon Beta 1b3.96 Raw score2.56 (Standard Error)28

Fingolimod

5.93

Interferon Beta 1b

3.96

p = 0.5183; Mean Difference (Net) 1.97 (95% CI -4.06–7.99)

Change From Screening in Spatial Recall Test (SPART) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod1.46 Raw score0.52 (Standard Error)80
Interferon Beta 1b3.06 Raw score0.89 (Standard Error)28

Fingolimod

1.46

Interferon Beta 1b

3.06

p = 0.1334; Mean Difference (Net) -1.60 (95% CI -3.69–0.50)

Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod2.19 Raw score1.12 (Standard Error)80
Interferon Beta 1b3.93 Raw score1.93 (Standard Error)28

Fingolimod

2.19

Interferon Beta 1b

3.93

p = 0.4501; Mean Difference (Net) -1.73 (95% CI -6.27–2.81)

Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod7.14 Raw score1.24 (Standard Error)80
Interferon Beta 1b6.68 Raw score2.13 (Standard Error)28

Fingolimod

7.14

Interferon Beta 1b

6.68

p = 0.8561; Mean Difference (Net) 0.46 (95% CI -4.57–5.49)

Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod4.79 Raw score1.25 (Standard Error)80
Interferon Beta 1b4.42 Raw score2.14 (Standard Error)28

Fingolimod

4.79

Interferon Beta 1b

4.42

p = 0.8858; Mean Difference (Net) 0.37 (95% CI -4.67–5.40)

Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod0.57 Raw score0.23 (Standard Error)80
Interferon Beta 1b0.39 Raw score0.4 (Standard Error)28

Fingolimod

0.57

Interferon Beta 1b

0.39

p = 0.7119; Mean Difference (Net) 0.17 (95% CI -0.76–1.11)

Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod0.41 Raw score0.21 (Standard Error)80
Interferon Beta 1b0.44 Raw score0.36 (Standard Error)28

Fingolimod

0.41

Interferon Beta 1b

0.44

p = 0.9496; Mean Difference (Net) -0.03 (95% CI -0.86–0.81)

Change From Screening in Word List Generation (WLG)

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod0.39 Raw score0.58 (Standard Error)80
Interferon Beta 1b0.24 Raw score0.99 (Standard Error)28

Fingolimod

0.39

Interferon Beta 1b

0.24

p = 0.8944; Mean Difference (Net) 0.16 (95% CI -2.18–2.50)

Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod0.57 Raw score0.31 (Standard Error)80
Interferon Beta 1b0.82 Raw score0.48 (Standard Error)28

Fingolimod

0.57

Interferon Beta 1b

0.82

p = 0.6757; Mean Difference (Net) -0.25 (95% CI -1.42–0.92)

Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod1.52 Raw score1.23 (Standard Error)80
Interferon Beta 1b3.69 Raw score1.92 (Standard Error)28

Fingolimod

1.52

Interferon Beta 1b

3.69

p = 0.3585; Mean Difference (Net) -2.16 (95% CI -6.82–2.50)

Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2

Screening (-1month), 18 month

GroupValueIntervalNumber analysed
Fingolimod2.15 Raw score1.9 (Standard Error)80
Interferon Beta 1b7.38 Raw score2.97 (Standard Error)28

Fingolimod

2.15

Interferon Beta 1b

7.38

p = 0.1610; Mean Difference (Net) -5.24 (95% CI -12.62–2.14)

Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.

Safety

GroupParticipants at riskSerious adverse eventsDeaths
Fingolimod 0.5 mg1049 (8.7%)
Interferon Beta 1b471 (2.1%)

As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.

What it measured

Main measures

  • Change From Screening in Selective Reminding Test - Long-Term Storage (SRT-LTS) Raw Score

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in Selective Reminding Test - Consistent Long Term Retrieval (SRT-CLTR) Raw Score

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in Spatial Recall Test (SPART) Raw Score

    Screening (-1month), 18 month

  • Change From Screening in Symbol Digit Modalities Test (SDMT) Raw Score

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in Paced Auditory Serial Addition Test - 3 Seconds (PASAT 3) Raw Score

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in Paced Auditory Serial Addition Test - 2 (PASAT 2) Raw Score

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in Selective Reminding Test - Delayed Recall (SRT-D) Raw Score

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in Spatial Recall Test - Delayed Recall (SPART-D)

    Screening (-1month), 18 month

  • Change From Screening in Word List Generation (WLG)

    Screening (-1month), 18 month

  • Change From Screening in Delis-Kaplan Executive Function System (DKEFS) Condition 1: Free Sorting, Confirmed Correct Sort- Card Set 1+2

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in DKEFS Condition 1: Free Sorting, Free Sorting, Description Score, Card Set 1+2

    Screening (-1month), 18 month

    Thinking and memory

  • Change From Screening in DKEFS Condition 2: Sort Recognition, Sort Recognition Description Score- Card Set 1+2

    Screening (-1month), 18 month

    Thinking and memory

  • The primary objective of the study is to evaluate the reduction of cognitive dysfunction progression in RRMS patients after 18 months of treatment with fingolimod in comparison with interferon beta 1b treatment and to evaluate which test is most sensitive in detecting differences between treatment groups.

    Thinking and memoryImmune response

Other measures (9)

  • Change From Screening in the Volume of Total T2 Lesions

    Screening (-1 month), 18 months

    MRI lesions

  • Change From Screening in Montgomery-Asberg Depression Rating Scale (MADRS)

    Screening (-1month), 18 month

    Mood and sleep

  • Changes in Quality of Life, by Means of the Multiple Sclerosis Quality of Life (MSQoL-54)

    Baseline, 18 months

    Thinking and memoryQuality of life (reported by participants)

  • Changes From Baseline in Fatigue Impact Scale (mFIS, Total Score and Scores of the 3 Individual Domains).

    Baseline, 18 months

    Thinking and memoryFatigue

  • Change From Screening in the Number of New T2 Lesions

    Screening (-1month), 18 month

    MRI lesions

  • Change From Screening in the Volume of Total T1 Hypointense Lesions

    Screening (-1month), 18 month

    MRI lesions

  • Change From Screening in the Number of T1 Gd+ Enhancing Lesions

    Screening (-1month), 18 month

    MRI lesions

  • Change From Screening in the Percentage of Brain Volume Change

    Screening (-1month), 18 month

    MRI lesionsBrain volume loss

  • Changes in the Environmental Status Scale Score (ESS)

    Baseline, 18 month

Who could take part

Relapsing MS · 18 to 50

Inclusion Criteria: * Patients with relapsing-remitting forms of MS defined by 2005 revised McDonald criteria. * Patients with active disease, defined as at least one clinical relapse in the last year, or two clinical relapses in the last two years if there are signs of disease activity at one brain MRI scan performed in the last six months. * Patients with cognitive impairment at screening, defined as at least one test of the Rao's Brief Repeatable Battery with scores falling outside the 90th percentile of the normative data. Exclusion Criteria: * Patients who had already been treated with multiweekly interferon (interferon beta 1b, or beta 1a multiweekly) and had an unsatisfactory response according to the judgment of the investigator. * Patients with hyperactive forms of the MS disease according to the judgment of the investigator. * Patients with an EDSS score higher than 5. * Patients with a prior or current diagnosis of Major Depression according to DSM-IV. * Patients with a history of chronic disease of the immune system other than MS such as known immunodeficiency syndrome. Other protocol-defined inclusion/exclusion criteria may apply

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

The purpose of this pilot study is to evaluate, by means of a specific cognitive test battery (Brief Repeatable Battery and Delis-Kaplan Executive Function System scale), the slowing/reduction of cognitive dysfunction progression in RRMS patients after 18 months of treatment with fingolimod in comparison with interferon beta 1b treatment, and to evaluate which test of the battery is the most sensitive in detecting differences between treatment groups.

Papers

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Related trials

History

    1. Started

      May 2011

    2. Main results due

      Sept 2015

    3. Finished

      Sept 2015

    4. Results posted

      Mar 2017

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