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Long-term Follow-up of Fingolimod Phase II Study Patients (ACROSS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02307838
Recruitment Status : Completed
First Posted : December 4, 2014
Results First Posted : March 23, 2017
Last Update Posted : March 23, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE May 14, 2014
First Posted Date  ICMJE December 4, 2014
Results First Submitted Date  ICMJE November 28, 2016
Results First Posted Date  ICMJE March 23, 2017
Last Update Posted Date March 23, 2017
Study Start Date  ICMJE June 2014
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 2, 2017)
Change From Baseline (BL) in Expanded Disability Status Scale (EDSS) [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A negative change from baseline indicates improvement.
Original Primary Outcome Measures  ICMJE
 (submitted: December 1, 2014)
Change from baseline in Expanded Disability Status Scale (EDSS) at 10 year [ Time Frame: 10 years ]
EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 2, 2017)
  • Number of Participants With Disability Progression [ Time Frame: 10 Years ]
    Disability progression is defined as: 1.5-point increase from baseline in participants with baseline EDSS score = 0.0; OR 1-point increase in EDSS from baseline in participants with baseline EDSS score of 1.0 to 5.0 inclusive; OR 0.5-point increase in EDSS from baseline in participants with baseline EDSS score >5.0.
  • Number of Participants With EDSS <4 or <6 [ Time Frame: 10 years ]
    EDSS is a scale for assessing neurologic impairment in MS. It consists of eight functional systems (FS) which are used to derive the EDSS steps (score) ranging from 0 (normal) to 10 (death due to MS). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Based on the assessment of each FS, the participant's score is determined between 0 to 10. A positive change from baseline indicates improvement.
  • Number of Participants Not Using a Wheelchair or Being Bedridden [ Time Frame: 10 years ]
    The number of participants not using a wheelchair or being bedridden was assessed.
  • Number of Participants Classified as Secondary Progressive MS (SPMS) [ Time Frame: 10 years ]
    SPMS follows an initial relapsing-remitting course. Most people who are diagnosed with relapsing-remitting multiple sclerosis (RRMS) will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function (accumulation of disability) over time. Participants who were classified as SPMS were assessed.
  • Percentage of Participants With First Use of an Ambulatory Device [ Time Frame: 10 years ]
    First use of an ambulatory device was considered from EDSS 6.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 6.0.
  • Percentage of Participants With First Use of a Wheelchair [ Time Frame: 10 years ]
    First use of a wheelchair was considered from EDSS 7.0 for participants having started FTY720D2201 (NCT00333138) with an EDSS score below 7.0.
  • Change From Baseline in Multiple Sclerosis Fuctional Composite (MSFC) Component: Nine Hole Peg Test (9-HPT) [ Time Frame: baseline from core study, CFTY720D2201 (NCT00333138), 10 years ]
    The 9-HPT is a quantitative measure of upper extremity (arm and hand) function. Both the dominant and non-dominant hands are tested twice (two consecutive trials of the dominant hand, followed immediately by two consecutive trials of the non-dominant hand). The time limit per trial is 300 seconds. The right and left hand scores were the time in seconds it took to insert and remove 9 pegs ((the average scores from the four trials on the 9-HPT (the two trials for each hand are averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals are averaged)). A negative change from baseline indicates improvement.
  • Change From Baseline in MSFC Component: Paced Auditory Serial Addition Test (PASAT) Score [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
    The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. The PASAT is the last measure administered at each visit. It is presented on audio compact disc (CD) to control the rate of stimulus presentation. Single digits are presented every 3 seconds and the patient must add each new digit to the one immediately prior to it. The test result is the number of correct sums given (out of 60 possible). A positive change from baseline indicates improvement.
  • Change From Baseline in MSFC Component: Timed 25-foot Walk Test Score [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
    The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The patient is directed to one end of a clearly marked 25-foot (7.62 m) course and is instructed to walk 25 feet (7.62 meter) as quickly as possible, but safely. The task is immediately administered again by having the patient walk back the same distance. Patients may use assistive devices when doing this task. The test scores were the time in seconds it took to walk the 25 feet. A negative change from baseline indicates improvement.
  • Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Z Score [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
    MSFC is a composite measure encompassing information from the nine-hole peg test (arm dimension), timed 25 foot walk (leg dimension) and PASAT. The MSFC composite Z score was calculated as follows: (1) the average scores from the four trials on the 9-HPT (the two trials for each hand were averaged, converted to the reciprocals of the mean times for each hand and then the two reciprocals were averaged); (2) the average scores of two 25-Foot Timed Walk trials; (3) the number correct from the PASAT-3. The MSFC is based on the concept that scores for these three dimensions-arm, leg, and cognitive function are combined to create a single score (the MSFC) that can be used to detect change over time in a group of multiple sclerosis patients. This was done by creating Z-scores for each component of the MSFC, and averaging them to create an overall composite Z score.
  • Total Volume in T2 Lesion [ Time Frame: 10 years ]
    Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI).
  • Change From Baseline in Total Volume of T2 Lesion [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
    Total volume in T2 lesion was assessed by magnetic resonance imaging (MRI). A negative change from baseline indicates improvement.
  • Third Ventricle Diameter [ Time Frame: 10 years ]
    Third ventricle diameter was assessed by MRI.
  • Change From Baseline in Third Ventricle Diameter [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
    Third ventricle diameter was assessed by MRI. A negative change from baseline indicates improvement.
  • Percentage Brain Volume Change (PBVC) [ Time Frame: baseline from core study (CFTY720D2201 (NCT00333138)), 10 years ]
    PVBC was assessed by MRI. A negative change from baseline indicates improvement.
  • Correlation Coeffcients Between FTY Treatment Duration and Disability Progression Parameters [ Time Frame: 10 years ]
    The correlation between FTY treatment duration and disability progression outcomes was assessed. The number presented in the table is the Pearson correlation coefficient, r.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 1, 2014)
  • Proportion of patients with disability progression at 10 years [ Time Frame: 10 Years ]
    Disability progression is defined as: 1.5-point increase from baseline in subjects with baseline EDSS score = 0.0; OR 1-point increase in EDSS from baseline in subjects with baseline EDSS score of 1.0 to 5.0 inclusive; OR 0.5-point increase in EDSS from baseline in subjects with baseline EDSS score >5.0.
  • Magnetic Resonance Imaging (MRI) [ Time Frame: 10 Years ]
    To assess various MRI parameters compared to Phase II baseline scans or as novel endpoints.
  • Correlational analyses 1 - Duration od treatment with clinical outcomes [ Time Frame: 10 Year ]
    Correlation analyses of fingolimod treatment duration and the disability progression outcomes, such as EDSS score at Year 10, First use of an ambulatory device and First documentation of Secondary Progressive Multiple Sclerosis (SPMS), will be performed for continous and non-continuous fingolimod use.
  • Correlational analyses 2 - MRI measures with clinical outcomes [ Time Frame: 10 Year ]
    Correlation analyses of MRI measures and clinical outcomes with the disability progression outcomes, such as EDSS score at Year 10, First use of an ambulatory device and First documentation of SPMS, will be performed for continous and non-continuous fingolimod use.
  • Correlational analyses 3 - Cognitive measures with MRI outcomes [ Time Frame: 10 Year ]
    Correlation analyses of change from Baseline at Year 10 Paced Auditory Serial Addition Test-3 (PASAT-3) score and the protocol specified MRI measures will be performed for continous and non-continuous fingolimod use.
  • Correlational analyses 4 - Atrophy measures comparing results with old MRI scanner at 10 years [ Time Frame: 10 Year ]
    Correlation analyses of atrophy measures at Year 10 on the same MRI scanner used for the D2201/ 2201E1 study and the same measure using the new MRI scanner will be performed for continous and non-continuous fingolimod use.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: December 1, 2014)
  • Disability [ Time Frame: 10 years ]
    To assess disability using milestone measurements within the EDSS and MSFC
  • MRI [ Time Frame: 10 years ]
    To assess various MRI parameters compared to Phase II baseline scans or as novel endpoints
  • Correlational analyses [ Time Frame: 10 years ]
    To assess the relationship between duration of treatment and cognitive measures with MRI and clinical outcomes
 
Descriptive Information
Brief Title  ICMJE Long-term Follow-up of Fingolimod Phase II Study Patients
Official Title  ICMJE Long-term Follow-up at 10 Years of Patients Enrolled in the Fingolimod Phase II Program in Relapsing Multiple Sclerosis (MS)
Brief Summary This study collected follow-up data on approximately 90% of participants who were randomized and received one dose of study drug in FTY720D2201 (D2201). No study drug was given or required. Participants were required to be assessed at one or two visits, preferably at the original study site, but the option to be interviewed via phone or seen at home was provided. Information was gathered also on deceased participants. Assessments were performed only once within an 8 week period and included medical history, Multiple Sclerosis (MS) and Multiple Sclerosis Disease Modifying Therapy (MS DMT) history, Expanded Disability Status Scale (EDSS), Magnetic Resonance Imaging (MRI), and Multiple Sclerosis Functional Composite (MSFC).
Detailed Description This was a multicenter follow-up study of patients originally enrolled in the Phase 2 D2201 study. Patients did not receive any protocol specified treatment. The original D2201 study sites who agreed to participate in this study were required to locate their patients who were randomized in Study D2201 and asked them to return for a 10-year assessment, regardless of their current treatment status. Locating the patient may have required the use of search and advertising strategies to find those patients currently lost to follow-up, in accordance with local privacy legislation. Patients currently being followed within Study FTY720D2399 (NCT01201356) were asked to participate in Study FTY720D2201E2 and if patients gave consent, were enrolled concurrently in both studies.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Multiple Sclerosis, Relapsing Forms of Multiple Sclerosis
Intervention  ICMJE Other: Assessments arm
Protocol required assessments not provided in standard of care
Study Arms  ICMJE Phase 2 CFTY720D2201 (NCT02307838) participants
CFTY720D2201E2 participants did not receive any protocol specified treatment. The original D2201 study sites, who agreed to participate in this study, were required to locate their participants who were randomized in D2201 and asked them to return for a 10 year assessment, regardless of current treatment status.
Intervention: Other: Assessments arm
Publications * Not Provided

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: January 15, 2016)
177
Original Estimated Enrollment  ICMJE
 (submitted: December 1, 2014)
281
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Written informed consent must be obtained before any assessment is performed.
  • Randomized in study FTY720D2201 and received at least one dose of study drug.

Exclusion Criteria:

  • None
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Denmark,   France,   Germany,   Italy,   Poland,   Portugal,   Spain,   Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02307838
Other Study ID Numbers  ICMJE CFTY720D2201E2
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
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 February 2017

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