Clinical trial NCT01895335: Using Patient Reported Outcomes (PROs) to Evaluate Teriflunomide Treatment in Relapsing Multiple Sclerosis (RMS) Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2013-07-10
Enrollment: 1001
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 - Assessment of Global Satisfaction Subscale Score With Teriflunomide Treatment at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Change From Baseline in TSQM Scores in Participants Switching From Another Disease Modifying Therapy (DMT) at Week 4 and Week 48
timeFrame: Baseline, Week 4, Week 48
measure: Change From Week 4 in TSQM Scores in Naïve Participants to Week 48
timeFrame: Week 4, Week 48
measure: Change From Baseline in Disease Progression Using Patient Determined Disease Steps (PDDS) Score at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Multiple Sclerosis Performance Scale (MSPS) Score at Week 24 and Week 48
timeFrame: Baseline, Week 24, Week 48
measure: Annualized Treated Relapse Rate
timeFrame: Baseline up to end of treatment (up to Week 48)
measure: Time to Relapse: Kaplan-Meier Estimates of the Probability of Treated Relapse at Week 4, Week 24 and Week 48
timeFrame: Baseline up to end of treatment (up to Week 48)
measure: Change From Baseline in Cognition Measured by Symbol Digit Modalities Test (SDMT) Score at Week 48
timeFrame: Baseline, Week 48
measure: Overview of Adverse Events (AEs)
timeFrame: 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
measure: Percentage of Participants With Treatment Compliance of ≥80% During the Study Treatment Period
timeFrame: Baseline up to end of treatment (up to Week 48)
measure: Duration of Teriflunomide Treatment Exposure
timeFrame: Baseline up to end of treatment (up to Week 48)
measure: Change From Baseline in Multiple Sclerosis International Quality of Life (MusiQoL) Score at Week 48
timeFrame: Baseline, Week 48
measure: Change From Baseline in Stern Leisure Activity Scale at Week 48
timeFrame: Baseline, Week 48
measure: Expanded Disability Status Scale (EDSS) Score at Baseline and Week 48
timeFrame: Baseline, Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840077
state: Alabama
city: Cullman
country: United States
facility: Investigational Site Number 840007
state: Alabama
city: Phoenix
country: United States
facility: Investigational Site Number 840087
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840114
state: Arizona
city: Scottsdale
country: United States
facility: Investigational Site Number 840080
state: Arizona
city: Tucson
country: United States
facility: Investigational Site Number 840032
state: Arizona
city: Phoenix
country: United States
facility: Investigational Site Number 840021
state: Arkansas
city: Fullerton
country: United States
facility: Investigational Site Number 840018
state: California
city: Fullerton
country: United States
facility: Investigational Site Number 840037
state: California
city: Long Beach
country: United States
facility: Investigational Site Number 840108
state: California
city: Newport Beach
country: United States
facility: Investigational Site Number 840014
state: California
city: Oceanside
country: United States
facility: Investigational Site Number 840019
state: California
city: Boulder
country: United States
facility: Investigational Site Number 840097
state: Colorado
city: Colorado Springs
country: United States
facility: Investigational Site Number 840040
state: Colorado
city: Denver
country: United States
facility: Investigational Site Number 840046
state: Colorado
city: Englewood
country: United States
facility: Investigational Site Number 840016
state: Colorado
city: Fort Collins
country: United States
facility: Investigational Site Number 840094
state: Colorado
city: Bradenton
country: United States
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state: Florida
city: Clearwater
country: United States
facility: Investigational Site Number 840089
state: Florida
city: Coconut Creek
country: United States
facility: Investigational Site Number 840055
state: Florida
city: Hialeah
country: United States
facility: Investigational Site Number 840104
state: Florida
city: Miami Lakes
country: United States
facility: Investigational Site Number 840101
state: Florida
city: Ormond Beach
country: United States
facility: Investigational Site Number 840011
state: Florida
city: Sarasota
country: United States
facility: Investigational Site Number 840059
state: Florida
city: St. Petersburg
country: United States
facility: Investigational Site Number 840008
state: Florida
city: Sunrise
country: United States
facility: Investigational Site Number 840081
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number 840002
state: Georgia
city: Macon
country: United States
facility: Investigational Site Number 840075
state: Georgia
city: Fort Wayne
country: United States
facility: Investigational Site Number 840012
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Site Number 840010
state: Indiana
city: Louisville
country: United States
facility: Investigational Site Number 840034
state: Kentucky
city: Rockport
country: United States
facility: Investigational Site Number 840047
state: Maine
city: Foxboro
country: United States
facility: Investigational Site Number 840107
state: Massachusetts
city: Springfield
country: United States
facility: Investigational Site Number 840030
state: Massachusetts
city: Clinton Township
country: United States
facility: Investigational Site Number 840073
state: Michigan
city: Golden Valley
country: United States
facility: Investigational Site Number 840068
state: Minnesota
city: Golden Valley
country: United States
facility: Investigational Site Number 840098
state: Minnesota
city: Chesterfield
country: United States
facility: Investigational Site Number 840086
state: Missouri
city: St. Louis
country: United States
facility: Investigational Site Number 840058
state: Missouri
city: Lincoln
country: United States
facility: Investigational Site Number 840026
state: Nebraska
city: Henderson
country: United States
facility: Investigational Site Number 840020
state: Nevada
city: Freehold
country: United States
facility: Investigational Site Number 840049
state: New Jersey
city: Toms River
country: United States
facility: Investigational Site Number 840044
state: New Jersey
city: East Setauket
country: United States
facility: Investigational Site Number 840100
state: New York
city: New York
country: United States
facility: Investigational Site Number 840005
state: New York
city: NY
country: United States
facility: Investigational Site Number 840064
state: New York
city: Schenectady
country: United States
facility: Investigational Site Number 840071
state: New York
city: Staten Island
country: United States
facility: Investigational Site Number 840091
state: New York
city: Syracuse
country: United States
facility: Investigational Site Number 840045
state: New York
city: Asheville
country: United States
facility: Investigational Site Number 840084
state: North Carolina
city: Charlotte
country: United States
facility: Investigational Site Number 840078
state: North Carolina
city: Raliegh
country: United States
facility: Investigational Site Number 840042
state: North Carolina
city: Sanford
country: United States
facility: Investigational Site Number 840105
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 840074
state: North Carolina
city: Winston Salem
country: United States
facility: Investigational Site Number 840090
state: North Carolina
city: Bismarck
country: United States
facility: Investigational Site Number 840041
state: North Dakota
city: Canton
country: United States
facility: Investigational Site Number 840003
state: Ohio
city: Dayton
country: United States
facility: Investigational Site Number 840009
state: Ohio
city: Monaca
country: United States
facility: Investigational Site Number 840053
state: Pennsylvania
city: Philadelphia
country: United States
facility: Investigational Site Number 840056
state: Pennsylvania
city: Cranston
country: United States
facility: Investigational Site Number 840072
state: Rhode Island
city: Nashville
country: United States
facility: Investigational Site Number 840048
state: Tennessee
city: Tullahoma
country: United States
facility: Investigational Site Number 840035
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 840060
state: Texas
city: Mansfield
country: United States
facility: Investigational Site Number 840052
state: Texas
city: San Antonio
country: United States
facility: Investigational Site Number 840028
state: Texas
city: Henrico
country: United States
facility: Investigational Site Number 840070
state: Virginia
city: Richmond
country: United States
facility: Investigational Site Number 840109
state: Virginia
city: Roanoke
country: United States
facility: Investigational Site Number 840017
state: Virginia
city: Vienna
country: United States
facility: Investigational Site Number 840054
state: Virginia
city: Spokane
country: United States
facility: Investigational Site Number 840069
state: Washington
city: Morgantown
country: United States
facility: Investigational Site Number 840079
state: West Virginia
city: Milwaukee
country: United States
facility: Investigational Site Number 840038
state: Wisconsin
city: Milwaukee
country: United States
facility: Investigational Site Number 840112
state: Wisconsin
city: Neenah
country: United States
facility: Investigational Site Number 840076
state: Wisconsin
city: Linz
country: Austria
facility: Investigational Site Number 040-001
city: Wien
country: Austria
facility: Investigational Site Number 040-002
city: Brasschaat
country: Belgium
facility: Investigational Site Number 056006
city: Bruxelles
country: Belgium
facility: Investigational Site Number 056001
city: Edegem
country: Belgium
facility: Investigational Site Number 056003
city: Kortrijk
country: Belgium
facility: Investigational Site Number 056002
city: Leuven
country: Belgium
facility: Investigational Site Number 056007
city: Liège
country: Belgium
facility: Investigational Site Number 056008
city: Liège
country: Belgium
facility: Investigational Site Number 056009
city: Melsbroek
country: Belgium
facility: Investigational Site Number 056005
city: Cambridge
country: Canada
facility: Investigational Site Number 124006
city: St. John
country: Canada
facility: Investigational Site Number 124007
city: Concepcion
country: Chile
facility: Investigational Site Number 152003
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Santiago
country: Chile
facility: Investigational Site Number 152005
city: Hämeenlinna
country: Finland
facility: Investigational Site Number 246004
city: Kuopio
country: Finland
facility: Investigational Site Number 246005
city: Oulu
country: Finland
facility: Investigational Site Number 246006
city: Turku
country: Finland
facility: Investigational Site Number 246001
city: Turku
country: Finland
facility: Investigational Site Number 246003
city: Agen Cedex
country: France
facility: Investigational Site Number 250002
city: Aix En Provence
country: France
facility: Investigational Site Number 250003
city: Albi
country: France
facility: Investigational Site Number 250004
city: Amiens Cedex 1
country: France
facility: Investigational Site Number 250005
city: Bayonne
country: France
facility: Investigational Site Number 250006
city: Bordeaux
country: France
facility: Investigational Site Number 250007
city: Caen
country: France
facility: Investigational Site Number 250008
city: CAHORS Cedex 9
country: France
facility: Investigational Site Number 250009
city: Chambery
country: France
facility: Investigational Site Number 250011
city: Colmar
country: France
facility: Investigational Site Number 250012
city: Dijon
country: France
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city: GRENOBLE cedex
country: France
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city: Le Mans Cedex 9
country: France
facility: Investigational Site Number 250017
city: Lille Cedex
country: France
facility: Investigational Site Number 250018
city: Limoges Cedex
country: France
facility: Investigational Site Number 250019
city: Lyon Cedex 03
country: France
facility: Investigational Site Number 250020
city: Marseille
country: France
facility: Investigational Site Number 250021
city: Metz-Tessy
country: France
facility: Investigational Site Number 250022
city: Montbeliard
country: France
facility: Investigational Site Number 250023
city: MONTPELLIER Cedex 5
country: France
facility: Investigational Site Number 250024
city: Mulhouse
country: France
facility: Investigational Site Number 250025
city: Nancy
country: France
facility: Investigational Site Number 250026
city: Nantes
country: France
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city: Nimes
country: France
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city: PARIS Cedex 13
country: France
facility: Investigational Site Number 250016
city: PARIS Cedex 20
country: France
facility: Investigational Site Number 250029
city: Pau
country: France
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city: Quimper
country: France
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city: Reims
country: France
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city: Rouen
country: France
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city: St Germain En Laye
country: France
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city: Strasbourg
country: France
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city: Toulouse
country: France
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city: Tours
country: France
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city: Valence Cedex 9
country: France
facility: Investigational Site Number 250039
city: Valenciennes
country: France
facility: Investigational Site Number 250040
city: VICHY Cedex
country: France
facility: Investigational Site Number 250013
city: Bergisch-Gladbach
country: Germany
facility: Investigational Site Number 276001
city: Berlin
country: Germany
facility: Investigational Site Number 276003
city: Freiburg
country: Germany
facility: Investigational Site Number 276004
city: Athens
country: Greece
facility: Investigational Site Number 300002
city: Athens
country: Greece
facility: Investigational Site Number 300001
city: Larissa
country: Greece
facility: Investigational Site Number 300005
city: Thessaloniki
country: Greece
facility: Investigational Site Number 300004
city: Ancona
country: Italy
facility: Investigational Site Number 380008
city: Bari
country: Italy
facility: Investigational Site Number 380009
city: Gallarate (VA)
country: Italy
facility: Investigational Site Number 380002
city: Milano
country: Italy
facility: Investigational Site Number 380001
city: Milano
country: Italy
facility: Investigational Site Number 380004
city: Napoli
country: Italy
facility: Investigational Site Number 380006
city: Orbassano (TO)
country: Italy
facility: Investigational Site Number 380005
city: Bergen
country: Norway
facility: Investigational Site Number 578002
city: Namsos
country: Norway
facility: Investigational Site Number 578003
city: Oslo
country: Norway
facility: Investigational Site Number 578001
city: Barcelona
country: Spain
facility: Investigational Site Number 724002
city: Córdoba
country: Spain
facility: Investigational Site Number 724010
city: Donostia
country: Spain
facility: Investigational Site Number 724008
city: El Palmar (MURCIA)
country: Spain
facility: Investigational Site Number 724001
city: La Coruña
country: Spain
facility: Investigational Site Number 724004
city: Santiago de Compostela
country: Spain
facility: Investigational Site Number 724006
city: Valencia
country: Spain
facility: Investigational Site Number 724007
city: Valladolid
country: Spain
facility: Investigational Site Number 724005
city: Karlstad
country: Sweden
facility: Investigational Site Number 752001
city: Kungsbacka
country: Sweden
facility: Investigational Site Number 752003
city: Motala
country: Sweden
facility: Investigational Site Number 752002
city: Birmingham
country: United Kingdom
facility: Investigational Site Number 826-005
city: Brighton
country: United Kingdom
facility: Investigational Site Number 826-003
city: Glasgow
country: United Kingdom
facility: Investigational Site Number 826-007
city: Leeds
country: United Kingdom
facility: Investigational Site Number 826-008
city: Leicester
country: United Kingdom
facility: Investigational Site Number 826-010
city: London
country: United Kingdom
facility: Investigational Site Number 826-009
city: Norwich
country: United Kingdom
facility: Investigational Site Number 826-001
city: Romford
country: United Kingdom
facility: Investigational Site Number 826-006
city: Salford
country: United Kingdom
facility: Investigational Site Number 826-004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Coyle PK, Khatri B, Edwards KR, Meca-Lallana JE, Cavalier S, Rufi P, Benamor M, Poole EM, Robinson M, Gold R. Teriflunomide real-world evidence: Global differences in the phase 4 Teri-PRO study. Mult Scler Relat Disord. 2019 Jun;31:157-164. doi: 10.1016/j.msard.2019.03.022. Epub 2019 Mar 30.
citation: Coyle PK, Khatri B, Edwards KR, Meca-Lallana JE, Cavalier S, Rufi P, Benamor M, Brette S, Robinson M, Gold R; Teri-PRO Trial Group. Patient-reported outcomes in relapsing forms of MS: Real-world, global treatment experience with teriflunomide from the Teri-PRO study. Mult Scler Relat Disord. 2017 Oct;17:107-115. doi: 10.1016/j.msard.2017.07.006. Epub 2017 Jul 6.