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

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective, Single-Arm, Clinical-Setting Study to Describe Efficacy, Tolerability and Convenience of Teriflunomide Treatment Using Patient Reported Outcomes (PROs) in Relapsing Multiple Sclerosis (RMS) Patients

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Teriflunomide


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Participants with a relapsing form of multiple sclerosis (RMS) having signed written informed consent. Exclusion criteria: According to local labelling, Less than 18 years of age, Current or history of receiving teriflunomide, Previous treatment with leflunomide within 6 months prior to baseline, Participants with preexisting acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) greater than 2 times the upper limit of normal (ULN), Known history of active tuberculosis (TB) or latent TB infection, either diagnosed by standard medical practice or guidelines (including skin or blood test, chest X-ray, or as appropriate per local practice), Known history of severe immunodeficiency, acquired immunodeficiency syndrome (AIDS), bone marrow disease, acute or severe active infections, Women who were pregnant or breast-feeding, Female participants with a positive pregnancy test at screening or women of child-bearing potential who did not agree to use reliable contraception throughout the course of the study, Male participants (only when required according to local labeling): unwilling to use reliable contraception during the course of the study, Additional exclusion criteria applicable for Europe (EU) countries (in accordance with contraindications of EU summary of product characteristics [SmPC]): Participants with significantly impaired bone marrow function or significant anaemia, leukopenia, neutropenia or thrombocytopenia, Participants with severe active infection until resolution, Participants with severe renal impairment undergoing dialysis, because insufficient clinical experience was available in this participant group, Participants with severe hypoproteinaemia, e.g. in nephrotic syndrome. Hypersensitivity to the active substance or to any of the excipients, Other additional contraindications per local labeling. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teriflunomide<br>Teriflunomide 14 mg or 7 mg according to local labelling once daily (QD) orally for 48 weeks. | Drug: Teriflunomide<br>* Pharmaceutical form: film-coated tablet; Route of administration: oral<br>* Other names: Aubagio®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 - Assessment of Global Satisfaction Subscale Score With Teriflunomide Treatment at 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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and 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 . | Baseline, Week 4, Week 48 | 
| Change From Week 4 in TSQM Scores in Naïve Participants to 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. | Week 4, Week 48 | 
| Change From Baseline in Disease Progression Using Patient Determined Disease Steps (PDDS) Score at 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. | Baseline, Week 48 | 
| Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and 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. | Baseline, Week 24, Week 48 | 
| Annualized Treated Relapse Rate | 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. | Baseline up to end of treatment (up to Week 48) | 
| Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and 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. | Baseline up to end of treatment (up to Week 48) | 
| Change From Baseline in Cognition Measured by Symbol Digit Modalities Test (SDMT) Score at 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. | Baseline, Week 48 | 
| Overview of Adverse Events (AEs) | 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. | 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 | 
| Percentage of Participants With Treatment Compliance of ≥80% During the Study Treatment Period | 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. | Baseline up to end of treatment (up to Week 48) | 
| Duration of Teriflunomide Treatment Exposure | 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). | Baseline up to end of treatment (up to Week 48) | 
| Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQoL) Score at 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. | Baseline, Week 48 | 
| Change From Baseline in Stern Leisure Activity Scale at 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. | Baseline, Week 48 | 
| Expanded Disability Status Scale (EDSS) Score at Baseline and 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. | Baseline, Week 48 |