Using Patient Reported Outcomes (PROs) to Evaluate Teriflunomide Treatment in Relapsing Multiple Sclerosis (RMS) Patients

Phase 4

Completed

Conditions: Multiple Sclerosis

Interventions: Drug: Teriflunomide

Registration Number: NCT01895335

Lead Sponsor: Sanofi

Brief Summary: Primary Objective:

To describe efficacy, tolerability and convenience of teriflunomide treatment through the evaluation of Participant Reported Outcomes (PROs).

Secondary Objectives:

To describe disease progression using PROs. To describe clinical outcomes (ie, treated relapses) in teriflunomide treated participant.

To describe the change in cognition in teriflunomide treated participants. To describe safety of teriflunomide in participant treated (based on adverse events reporting).

To describe adherence and persistence to teriflunomide treatment. To describe quality of life, activity and leisure over the period of teriflunomide treatment.

To compare Participant Determined Disease Steps (PDDS) and Expanded Disability Status Scale (EDSS) in assessing Multiple Sclerosis (MS) disease progression.

Detailed Description: The total duration of the study per participant was up to 50 or 54 weeks (if accelerated elimination procedure performed):

Screening: up to 2 weeks Teriflunomide treatment: 48 weeks Accelerated elimination procedure: 4 weeks when performed

An accelerated elimination procedure at any time after discontinuation of teriflunomide treatment was possible and it was particularly recommended for women of child-bearing potential.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1001

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Teriflunomide	Teriflunomide	Teriflunomide 14 mg or 7 mg according to local labelling once daily (QD) orally for 48 weeks.

Primary Outcome Measures

Name	Time	Method
Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 - Assessment of Global Satisfaction Subscale Score With Teriflunomide Treatment at Week 48	Week 48	TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions:12-14). Primary outcome was the global satisfaction score. The score of the corresponding item was added based on the algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and Week 48	Baseline, Week 24, Week 48	MSPS was a self-reported measure for MS associated disability in which participants were asked to indicate the category that best described their condition during the past month on the following 8 subscales: mobility, hand function, vision, fatigue, cognitive symptoms, bladder/bowel, sensory symptoms and spasticity symptoms. MSPS used a single question to assess each of 8 subscales. All of the subscales ranged from 0= normal to 5= total disability, except mobility subscale which ranged from 0= normal to 6=total disability. Total MSPS score ranged from 0 =normal to 41=greater disability, where higher score reflected greater disability.
Overview of Adverse Events (AEs)	From first study drug intake up to 112 days after last intake for participant with no AEP or to last AEP follow up visit for participants with AEP	Any untoward medical occurrence in a participant who received investigational medicinal product (IMP) was considered an AE without regard to possibility of causal relationship with this treatment. Treatment-emergent adverse events (TEAEs) were defined as AEs that developed or worsened or became serious during from first study drug intake up to 112 days after last intake for participant with no accelerated elimination procedure (AEP) or to last AEP follow up visit for participants with AEP. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life-threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious AEs.
Change From Baseline in Stern Leisure Activity Scale at Week 48	Baseline, Week 48	The Stern Leisure Activity Scale is a self-reported scale that consists of 13 questions assessing the participant's participation in leisure activities during the preceding month. One point is given for participation in each of the 13 activities and an aggregate score (range from 0 to 13) is obtained. ≤ 6 score is considered as low leisure activity and \> 6 score as high leisure activity.
Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48	Baseline, Week 4, Week 48	TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions: 12-14). For each of the 4 domains the scores of the corresponding items were added based on an algorithm to create a score of 0 to 100. Higher scores indicated greater satisfaction .
Change From Week 4 in TSQM Scores in Naïve Participants to Week 48	Week 4, Week 48	TSQM version 1.4 is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. It comprises of 14 items assessing the following 4 domains: effectiveness (questions: 1-3), side effects (questions: 4-8), convenience (questions: 9-11), global satisfaction (questions: 12-14). For each of the 4 domains the scores of the corresponding items were added based on an algorithm to create a score of 0 to 100. Higher scores indicated greater satisfaction.
Change From Baseline in Disease Progression Using Patient Determined Disease Steps (PDDS) Score at Week 48	Baseline, Week 48	PDDS scale developed to assess the disability in Multiple Sclerosis (MS) participants and in assessing disease progression that focuses mainly on how participants walk. PDDS scale consists of 0 = normal; 1 = mild disability; 2 = moderate disability; 3 = gait disability; 4 = early cane; 5 = late cane; 6 = bilateral support; 7 = wheelchair/scooter and 8 = bedridden. A higher score represented higher level of disability.
Duration of Teriflunomide Treatment Exposure	Baseline up to end of treatment (up to Week 48)	Duration of exposure was defined as last dose date - first dose date + 1 day, regardless of unplanned intermittent discontinuations and regardless of dosage administered (14 mg or 7 mg).
Annualized Treated Relapse Rate	Baseline up to end of treatment (up to Week 48)	Annualized treated relapse rate was defined as the total number of treated relapses during the study treatment period divided by the total number participants-years of treatment. Only events occurred during the treatment period (first drug administration to last drug administration) were considered for analysis.
Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48	Baseline up to end of treatment (up to Week 48)	A treated relapse was defined as a relapse treated by a systemic corticosteroid treatment or by another DMT. If a participant had no treated relapse before treatment discontinuation/completion, then the participant was considered as free of treated relapse until the date of treatment discontinuation/completion. Only treated relapse occurred during the treatment period (first drug administration to last drug administration) were considered for analysis. Kaplan-Meier method was used to estimate the probability of treated MS relapse at 4, 24 and 48 weeks.
Change From Baseline in Cognition Measured by Symbol Digit Modalities Test (SDMT) Score at Week 48	Baseline, Week 48	SDMT measures the time to pair abstract symbols with specific numbers. It is a simple substitution task that gives the examinee 90 seconds to pair specific numbers with given geometric figures as a measure for screening cognitive impairment. The score is computed as a ratio of number of correct responses divided by the total number of responses. The test score range from 0 (worst outcome) to 1 (best outcome). Higher scores are indicative of better cognition function.
Expanded Disability Status Scale (EDSS) Score at Baseline and Week 48	Baseline, Week 48	EDSS is a method of quantifying disability in MS participants and monitoring changes in the level of disability over time. EDSS quantifies disability in 8 functional systems: pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, cerebral, and other. EDSS scale ranges from 0 to 10 in 0.5 unit increments that represents higher levels of disability. EDSS score 1.0 to 4.5 refers to people with MS who are fully ambulatory; EDSS score 5.0 to 9.5 refers to impairment to ambulation; EDSS score 10 refers to death due to MS.
Percentage of Participants With Treatment Compliance of ≥80% During the Study Treatment Period	Baseline up to end of treatment (up to Week 48)	Percentage of compliance for a participant was defined as the number of days that the participant was compliant (1 tablet/day) divided by the exposure duration in days (from the first dose administration to the last dose administration) times 100.
Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQoL) Score at Week 48	Baseline, Week 48	The MusiQoL is a quality of life questionnaire that consists of 31 questions, divided into 9 dimensions: activities of daily living, physiological well-being, symptoms, relationship with friends, relationship with family, sentimental and sexual life, coping, rejection and relationship with healthcare system. All the 9 dimension scores and the global scores are linearly transformed and standardized on 0 (worst outcome) -100 (best outcome) scale. Higher scores represents higher quality of life.

Trial Locations

Locations (169): Investigational Site Number 840003
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Canton, Ohio, United States
Investigational Site Number 840037
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Fullerton, California, United States
Investigational Site Number 840104
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Hialeah, Florida, United States
Investigational Site Number 840101
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Miami Lakes, Florida, United States
Investigational Site Number 840008
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St. Petersburg, Florida, United States
Investigational Site Number 840086
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Chesterfield, Missouri, United States
Investigational Site Number 840045
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Syracuse, New York, United States
Investigational Site Number 840056
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Philadelphia, Pennsylvania, United States
Investigational Site Number 056003
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Edegem, Belgium
Investigational Site Number 056005
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Melsbroek, Belgium
Investigational Site Number 246006
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Oulu, Finland
Investigational Site Number 246005
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Kuopio, Finland
Investigational Site Number 578003
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Namsos, Norway
Investigational Site Number 578001
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Oslo, Norway
Investigational Site Number 840032
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Tucson, Arizona, United States
Investigational Site Number 840080
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Scottsdale, Arizona, United States
Investigational Site Number 840007
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Cullman, Alabama, United States
Investigational Site Number 840047
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Rockport, Maine, United States
Investigational Site Number 840073
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Clinton Township, Michigan, United States
Investigational Site Number 840002
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Atlanta, Georgia, United States
Investigational Site Number 840107
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Foxboro, Massachusetts, United States
Investigational Site Number 840018
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Fullerton, California, United States
Investigational Site Number 840075
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Macon, Georgia, United States
Investigational Site Number 840081
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Sunrise, Florida, United States
Investigational Site Number 840055
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Coconut Creek, Florida, United States
Investigational Site Number 056007
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Leuven, Belgium
Investigational Site Number 152005
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Santiago, Chile
Investigational Site Number 840068
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Golden Valley, Minnesota, United States
Investigational Site Number 840005
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New York, New York, United States
Investigational Site Number 124007
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St. John, Canada
Investigational Site Number 250004
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Albi, France
Investigational Site Number 840091
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Staten Island, New York, United States
Investigational Site Number 840084
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Asheville, North Carolina, United States
Investigational Site Number 040-002
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Wien, Austria
Investigational Site Number 056002
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Kortrijk, Belgium
Investigational Site Number 056009
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Liège, Belgium
Investigational Site Number 840079
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Morgantown, West Virginia, United States
Investigational Site Number 840069
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Spokane, Washington, United States
Investigational Site Number 250019
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Limoges Cedex, France
Investigational Site Number 840041
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Bismarck, North Dakota, United States
Investigational Site Number 040-001
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Linz, Austria
Investigational Site Number 152001
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Santiago, Chile
Investigational Site Number 840053
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Monaca, Pennsylvania, United States
Investigational Site Number 840105
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Sanford, North Carolina, United States
Investigational Site Number 840017
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Roanoke, Virginia, United States
Investigational Site Number 840052
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Mansfield, Texas, United States
Investigational Site Number 056006
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Brasschaat, Belgium
Investigational Site Number 250011
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Chambery, France
Investigational Site Number 056001
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Bruxelles, Belgium
Investigational Site Number 840060
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Dallas, Texas, United States
Investigational Site Number 840054
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Vienna, Virginia, United States
Investigational Site Number 840076
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Neenah, Wisconsin, United States
Investigational Site Number 250012
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Colmar, France
Investigational Site Number 300002
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Athens, Greece
Investigational Site Number 300001
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Athens, Greece
Investigational Site Number 056008
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Liège, Belgium
Investigational Site Number 752001
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Karlstad, Sweden
Investigational Site Number 380002
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Gallarate (VA), Italy
Investigational Site Number 380005
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Orbassano (TO), Italy
Investigational Site Number 724008
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Donostia, Spain
Investigational Site Number 250005
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Amiens Cedex 1, France
Investigational Site Number 276004
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Freiburg, Germany
Investigational Site Number 826-005
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Birmingham, United Kingdom
Investigational Site Number 276001
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Bergisch-Gladbach, Germany
Investigational Site Number 724002
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Barcelona, Spain
Investigational Site Number 578002
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Bergen, Norway
Investigational Site Number 724006
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Santiago de Compostela, Spain
Investigational Site Number 826-007
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Glasgow, United Kingdom
Investigational Site Number 724007
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Valencia, Spain
Investigational Site Number 380004
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Milano, Italy
Investigational Site Number 826-001
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Norwich, United Kingdom
Investigational Site Number 724004
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La Coruña, Spain
Investigational Site Number 826-008
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Leeds, United Kingdom
Investigational Site Number 300005
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Larissa, Greece
Investigational Site Number 724001
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El Palmar (MURCIA), Spain
Investigational Site Number 250040
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Valenciennes, France
Investigational Site Number 380008
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Ancona, Italy
Investigational Site Number 380009
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Bari, Italy
Investigational Site Number 380006
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Napoli, Italy
Investigational Site Number 752003
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Kungsbacka, Sweden
Investigational Site Number 250002
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Agen Cedex, France
Investigational Site Number 250003
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Aix En Provence, France
Investigational Site Number 250006
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Bayonne, France
Investigational Site Number 250009
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CAHORS Cedex 9, France
Investigational Site Number 250008
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Caen, France
Investigational Site Number 250007
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Bordeaux, France
Investigational Site Number 250001
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Dijon, France
Investigational Site Number 250021
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Marseille, France
Investigational Site Number 250017
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Le Mans Cedex 9, France
Investigational Site Number 250018
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Lille Cedex, France
Investigational Site Number 250043
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Pau, France
Investigational Site Number 250022
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Metz-Tessy, France
Investigational Site Number 250028
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Nimes, France
Investigational Site Number 250025
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Mulhouse, France
Investigational Site Number 250026
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Nancy, France
Investigational Site Number 250029
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PARIS Cedex 20, France
Investigational Site Number 250030
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St Germain En Laye, France
Investigational Site Number 250031
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Quimper, France
Investigational Site Number 250032
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Reims, France
Investigational Site Number 250037
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Toulouse, France
Investigational Site Number 250038
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Tours, France
Investigational Site Number 250013
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VICHY Cedex, France
Investigational Site Number 250039
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Valence Cedex 9, France
Investigational Site Number 840077
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Birmingham, Alabama, United States
Investigational Site Number 840087
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Phoenix, Arizona, United States
Investigational Site Number 840114
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Phoenix, Arizona, United States
Investigational Site Number 840046
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Denver, Colorado, United States
Investigational Site Number 840048
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Nashville, Tennessee, United States
Investigational Site Number 840028
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San Antonio, Texas, United States
Investigational Site Number 840010
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Indianapolis, Indiana, United States
Investigational Site Number 724005
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Valladolid, Spain
Investigational Site Number 840038
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Milwaukee, Wisconsin, United States
Investigational Site Number 840098
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Golden Valley, Minnesota, United States
Investigational Site Number 840016
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Englewood, Colorado, United States
Investigational Site Number 840030
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Springfield, Massachusetts, United States
Investigational Site Number 840026
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Lincoln, Nebraska, United States
Investigational Site Number 124006
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Cambridge, Canada
Investigational Site Number 840112
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Milwaukee, Wisconsin, United States
Investigational Site Number 840049
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Freehold, New Jersey, United States
Investigational Site Number 250020
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Lyon Cedex 03, France
Investigational Site Number 250016
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PARIS Cedex 13, France
Investigational Site Number 826-004
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Salford, United Kingdom
Investigational Site Number 840021
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Phoenix, Arkansas, United States
Investigational Site Number 840108
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Long Beach, California, United States
Investigational Site Number 840014
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Newport Beach, California, United States
Investigational Site Number 840097
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Boulder, Colorado, United States
Investigational Site Number 840024
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Bradenton, Florida, United States
Investigational Site Number 840094
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Fort Collins, Colorado, United States
Investigational Site Number 840089
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Clearwater, Florida, United States
Investigational Site Number 840011
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Ormond Beach, Florida, United States
Investigational Site Number 840059
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Sarasota, Florida, United States
Investigational Site Number 840044
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Toms River, New Jersey, United States
Investigational Site Number 840100
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East Setauket, New York, United States
Investigational Site Number 840064
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NY, New York, United States
Investigational Site Number 840071
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Schenectady, New York, United States
Investigational Site Number 840074
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Wilmington, North Carolina, United States
Investigational Site Number 840042
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Raliegh, North Carolina, United States
Investigational Site Number 840009
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Dayton, Ohio, United States
Investigational Site Number 840090
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Winston Salem, North Carolina, United States
Investigational Site Number 840072
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Cranston, Rhode Island, United States
Investigational Site Number 840035
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Tullahoma, Tennessee, United States
Investigational Site Number 840070
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Henrico, Virginia, United States
Investigational Site Number 250023
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Montbeliard, France
Investigational Site Number 250035
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Strasbourg, France
Investigational Site Number 300004
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Thessaloniki, Greece
Investigational Site Number 380001
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Milano, Italy
Investigational Site Number 724010
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Córdoba, Spain
Investigational Site Number 752002
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Motala, Sweden
Investigational Site Number 826-003
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Brighton, United Kingdom
Investigational Site Number 826-010
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Leicester, United Kingdom
Investigational Site Number 826-009
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London, United Kingdom
Investigational Site Number 826-006
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Romford, United Kingdom
Investigational Site Number 840019
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Oceanside, California, United States
Investigational Site Number 840040
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Colorado Springs, Colorado, United States
Investigational Site Number 840020
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Henderson, Nevada, United States
Investigational Site Number 250024
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MONTPELLIER Cedex 5, France
Investigational Site Number 840012
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Fort Wayne, Indiana, United States
Investigational Site Number 840058
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St. Louis, Missouri, United States
Investigational Site Number 840078
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Charlotte, North Carolina, United States
Investigational Site Number 250027
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Nantes, France
Investigational Site Number 250033
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Rouen, France
Investigational Site Number 250015
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GRENOBLE cedex, France
Investigational Site Number 152003
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Concepcion, Chile
Investigational Site Number 246004
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Hämeenlinna, Finland
Investigational Site Number 246001
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Turku, Finland
Investigational Site Number 246003
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Turku, Finland
Investigational Site Number 840034
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Louisville, Kentucky, United States
Investigational Site Number 840109
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Richmond, Virginia, United States
Investigational Site Number 276003
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Berlin, Germany