AzTrials
AzTrials

Multiple SclerosisPhase 3TOWERNCT00751881

An Efficacy Study of Teriflunomide in Participants With Relapsing Multiple Sclerosis

A Phase 3 study testing Teriflunomide in people with Multiple Sclerosis, run by Sanofi at 193 sites in 26 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

The primary objective of the study was to assess the effect of two doses of teriflunomide, in comparison to placebo, on the frequency of multiple sclerosis (MS) relapses in participants with relapsing MS. Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
Teriflunomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,169 participants
Where
193 sitesin 26 countries
Study dates
Aug 2008to Aug 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Relapsing multiple sclerosis,
  • Two relapses in prior 2 years or one relapse in prior year.

Who cannot join

  • Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease,
  • Significantly impaired bone marrow function or, significant anemia, leukopenia or thrombocytopenia,
  • Pregnant or nursing woman,
  • Alcohol or drug abuse,
  • Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate,
  • Human immunodeficiency virus (HIV) positive,
  • Any known condition or circumstance that would prevent, in the investigator's opinion, compliance or completion of the study.
  • The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial locations and contacts

193 sites in 26 countries.

193 sites in 26 countries

United States39 sites

  • Sanofi-Aventis Investigational Site Number 840006

    Bennington, Vermont, 05201

  • Sanofi-Aventis Investigational Site Number 840074

    Bismarck, North Dakota, 58501

  • Sanofi-Aventis Investigational Site Number 840020

    Charleston, West Virginia, 25301

  • Sanofi-Aventis Investigational Site Number 840029

    Charlotte, North Carolina, 28204

  • Sanofi-Aventis Investigational Site Number 840026

    Cincinnati, Ohio, 45219

  • Sanofi-Aventis Investigational Site Number 840069

    Clinton Township, Michigan, 48035

  • Sanofi-Aventis Investigational Site Number 840071

    Cordova, Tennessee, 38018

  • Sanofi-Aventis Investigational Site Number 840078

    Dayton, Ohio, 45409

  • Sanofi-Aventis Investigational Site Number 840016

    Des Moines, Iowa, 50314

  • Sanofi-Aventis Investigational Site Number 840063

    Elk Grove Village, Illinois, 60007

  • Sanofi-Aventis Investigational Site Number 840011

    Fairfield, Connecticut, 06430

  • Sanofi-Aventis Investigational Site Number 840064

    Flossmoor, Illinois, 60402

  • Sanofi-Aventis Investigational Site Number 840090

    Fort Collins, Colorado, 80528

  • Sanofi-Aventis Investigational Site Number 840039

    Fort Wayne, Indiana, 46804

  • Sanofi-Aventis Investigational Site Number 840075

    Grand Rapids, Michigan, 49503

  • Sanofi-Aventis Investigational Site Number 840068

    Greenville, South Carolina, 29615

  • Sanofi-Aventis Investigational Site Number 840012

    Indianapolis, Indiana, 46256

  • Sanofi-Aventis Investigational Site Number 840008

    Loma Linda, California, 92354

  • Sanofi-Aventis Investigational Site Number 840013

    Maitland, Florida, 32761

  • Sanofi-Aventis Investigational Site Number 840076

    Minneapolis, Minnesota, 55455

  • Sanofi-Aventis Investigational Site Number 840034

    Modesto, California, 95355

  • Sanofi-Aventis Investigational Site Number 840036

    Nashville, Tennessee, 37232

  • Sanofi-Aventis Investigational Site Number 840083

    Ocala, Florida, 34474

  • Sanofi-Aventis Investigational Site Number 840086

    Ormond Beach, Florida, 32174

  • Sanofi-Aventis Investigational Site Number 840073

    Philadelphia, Pennsylvania, 19102

  • Sanofi-Aventis Investigational Site Number 840022

    Philadelphia, Pennsylvania, 19107

  • Sanofi-Aventis Investigational Site Number 840041

    Phoenix, Arizona, 85060

  • Sanofi-Aventis Investigational Site Number 840024

    Portland, Oregon, 97225

  • Sanofi-Aventis Investigational Site Number 840007

    San Antonio, Texas, 78229

  • Sanofi-Aventis Investigational Site Number 840025

    Sarasota, Florida, 34239

  • Sanofi-Aventis Investigational Site Number 840089

    Seattle, Washington, 98122

  • Sanofi-Aventis Investigational Site Number 840088

    St Louis, Missouri, 63131

  • Sanofi-Aventis Investigational Site Number 840015

    St. Petersburg, Florida, 33606

  • Sanofi-Aventis Investigational Site Number 840033

    Sunrise, Florida, 33351

  • Sanofi-Aventis Investigational Site Number 840060

    Syracuse, New York, 13210

  • Sanofi-Aventis Investigational Site Number 840061

    Traverse City, Michigan, 49684

  • Sanofi-Aventis Investigational Site Number 840084

    Tucson, Arizona, 85741-3537

  • Sanofi-Aventis Investigational Site Number 840066

    Tulsa, Oklahoma, 74137

  • Sanofi-Aventis Investigational Site Number 840079

    Tupelo, Mississippi, 38801

Other trials in United States

China32 sites

  • Sanofi-Aventis Investigational Site Number 156023

    Baotou, 014010

  • Sanofi-Aventis Investigational Site Number 156031

    Beijing, 100034

  • Sanofi-Aventis Investigational Site Number 156006

    Beijing, 100050

  • Sanofi-Aventis Investigational Site Number 156010

    Beijing, 100050

  • Sanofi-Aventis Investigational Site Number 156005

    Beijing, 100053

  • Sanofi-Aventis Investigational Site Number 156032

    Beijing, 100068

  • Sanofi-Aventis Investigational Site Number 156024

    Beijing, 100088

  • Sanofi-Aventis Investigational Site Number 156030

    Beijing, 100191

  • Sanofi-Aventis Investigational Site Number 156001

    Beijing, 100730

  • Sanofi-Aventis Investigational Site Number 156008

    Beijing, 100853

  • Sanofi-Aventis Investigational Site Number 156007

    Changchun, 130021

  • Sanofi-Aventis Investigational Site Number 156002

    Chengdu, 610041

  • Sanofi-Aventis Investigational Site Number 156025

    Guangzhou, 510260

  • Sanofi-Aventis Investigational Site Number 156012

    Guangzhou, 510630

  • Sanofi-Aventis Investigational Site Number 156027

    Haikou, 570102

  • Sanofi-Aventis Investigational Site Number 156021

    Hangzhou, 310016

  • Sanofi-Aventis Investigational Site Number 156033

    Jinan, 250033

  • Sanofi-Aventis Investigational Site Number 156034

    Nanjing, 210008

  • Sanofi-Aventis Investigational Site Number 156011

    Nanjing, 210029

  • Sanofi-Aventis Investigational Site Number 156019

    Qingdao, 266003

  • Sanofi-Aventis Investigational Site Number 156029

    Shanghai, 200003

  • Sanofi-Aventis Investigational Site Number 156016

    Shanghai, 200040

  • Sanofi-Aventis Investigational Site Number 156009

    Shenyang, 110001

  • Sanofi-Aventis Investigational Site Number 156022

    Shijiazhuang, 050051

  • Sanofi-Aventis Investigational Site Number 156018

    Suzhou, 215006

  • Sanofi-Aventis Investigational Site Number 156028

    Taiyuan, 030001

  • Sanofi-Aventis Investigational Site Number 156003

    Tianjin, 300052

  • Sanofi-Aventis Investigational Site Number 156035

    Tianjin, 300211

  • Sanofi-Aventis Investigational Site Number 156017

    Wenzhou, 325000

  • Sanofi-Aventis Investigational Site Number 156004

    Wuhan, 430030

  • Sanofi-Aventis Investigational Site Number 156014

    Xi'an, 710032

  • Sanofi-Aventis Investigational Site Number 156015

    Xi'an, 710061

Other trials in China

Ukraine19 sites

  • Sanofi-Aventis Investigational Site Number 804101

    Chernihiv, 14025

  • Sanofi-Aventis Investigational Site Number 804103

    Dnipropetrovsk, 49027

  • Sanofi-Aventis Investigational Site Number 804107

    Donetsk, 83003

  • Sanofi-Aventis Investigational Site Number 804117

    Donetsk, 83099

  • Sanofi-Aventis Investigational Site Number 804119

    Ivano-Frankivsk, 76008

  • Sanofi-Aventis Investigational Site Number 804102

    Kharkiv, 61018

  • Sanofi-Aventis Investigational Site Number 804109

    Kharkiv, 61068

  • Sanofi-Aventis Investigational Site Number 804115

    Kiev, 04050

  • Sanofi-Aventis Investigational Site Number 804116

    Kiev, 04112

  • Sanofi-Aventis Investigational Site Number 804108

    Kiev

  • Sanofi-Aventis Investigational Site Number 804111

    Lutsk, 43005

  • Sanofi-Aventis Investigational Site Number 804124

    Lutsk, 43024

  • Sanofi-Aventis Investigational Site Number 804114

    Lviv, 79010

  • Sanofi-Aventis Investigational Site Number 804121

    Lviv, 79010

  • Sanofi-Aventis Investigational Site Number 804120

    Poltava, 36011

  • Sanofi-Aventis Investigational Site Number 804105

    Vinnytsia, 21005

  • Sanofi-Aventis Investigational Site Number 804118

    Zaporizhya, 69035

  • Sanofi-Aventis Investigational Site Number 804122

    Zaporizhzhya, 69000

  • Sanofi-Aventis Investigational Site Number 804104

    Zaporizhzhya, 69600

Other trials in Ukraine

Turkey (Türkiye)10 sites

  • Sanofi-Aventis Investigational Site Number 792011

    Edirne

  • Sanofi-Aventis Investigational Site Number 792009

    Istanbul, 34147

  • Sanofi-Aventis Investigational Site Number 792001

    Istanbul, 34390

  • Sanofi-Aventis Investigational Site Number 792007

    Istanbul

  • Sanofi-Aventis Investigational Site Number 792010

    Istanbul

  • Sanofi-Aventis Investigational Site Number 792012

    Izmir, 35380

  • Sanofi-Aventis Investigational Site Number 792002

    Kocaeli, 41380

  • Sanofi-Aventis Investigational Site Number 792003

    Manisa

  • Sanofi-Aventis Investigational Site Number 792005

    Samsun

  • Sanofi-Aventis Investigational Site Number 792004

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Germany9 sites

  • Sanofi-Aventis Investigational Site Number 276010

    Bamberg, 96047

  • Sanofi-Aventis Investigational Site Number 276003

    Bayreuth, 95445

  • Sanofi-Aventis Investigational Site Number 276005

    Berlin, 10713

  • Sanofi-Aventis Investigational Site Number 276001

    Erlangen, 91054

  • Sanofi-Aventis Investigational Site Number 276006

    Giessen, 35385

  • Sanofi-Aventis Investigational Site Number 276004

    Hanover, 30625

  • Sanofi-Aventis Investigational Site Number 276007

    Leipzig, 04157

  • Sanofi-Aventis Investigational Site Number 276009

    Magdeburg, 39120

  • Sanofi-Aventis Investigational Site Number 276002

    Wiesbaden, 65191

Other trials in Germany

Australia7 sites

  • Sanofi-Aventis Investigational Site Number 036005

    Bedford Park, 5042

  • Sanofi-Aventis Investigational Site Number 036006

    Chatswood, 2067

  • Sanofi-Aventis Investigational Site Number 036003

    Fitzroy, 3065

  • Sanofi-Aventis Investigational Site Number 036004

    Geelong, 3220

  • Sanofi-Aventis Investigational Site Number 036008

    Heidelberg, 3084

  • Sanofi-Aventis Investigational Site Number 036002

    New Lambton, 2305

  • Sanofi-Aventis Investigational Site Number 036001

    Sydney, 2050

Other trials in Australia

Canada7 sites

  • Sanofi-Aventis Investigational Site Number 124004

    Gatineau, J9J 0A5

  • Sanofi-Aventis Investigational Site Number 124002

    Kingston, K7L 2V7

  • Sanofi-Aventis Investigational Site Number 124007

    Montreal, H1T 2M4

  • Sanofi-Aventis Investigational Site Number 124008

    Ottawa, K2G 6E2

  • Sanofi-Aventis Investigational Site Number 124001

    Québec, G1J 1Z4

  • Sanofi-Aventis Investigational Site Number 124003

    Regina, S4T 1A5

  • Sanofi-Aventis Investigational Site Number 124006

    Saint John, E2L 3L6

Other trials in Canada

France7 sites

  • Sanofi-Aventis Investigational Site Number 250005

    Besançon, 25030

  • Sanofi-Aventis Investigational Site Number 250008

    Dijon, 21033

  • Sanofi-Aventis Investigational Site Number 250001

    Lyon, 69394

  • Sanofi-Aventis Investigational Site Number 250007

    Nantes, 44093

  • Sanofi-Aventis Investigational Site Number 250006

    Nice, 06002

  • Sanofi-Aventis Investigational Site Number 250002

    Nîmes, 30029

  • Sanofi-Aventis Investigational Site Number 250003

    Poissy, 78300

Other trials in France

Belarus5 sites

  • Sanofi-Aventis Investigational Site Number 112105

    Grodno

  • Sanofi-Aventis Investigational Site Number 112102

    Minsk, 220226

  • Sanofi-Aventis Investigational Site Number 112101

    Minsk

  • Sanofi-Aventis Investigational Site Number 112104

    Minsk

  • Sanofi-Aventis Investigational Site Number 112103

    Vitebsk

Other trials in Belarus

Netherlands5 sites

  • Sanofi-Aventis Investigational Site Number 528003

    's-Hertogenbosch, 5211 NL

  • Sanofi-Aventis Investigational Site Number 528001

    Breda, 4818 CK

  • Sanofi-Aventis Investigational Site Number 528002

    Groesbeek, 6561 KE

  • Sanofi-Aventis Investigational Site Number 528004

    Nieuwegein, 3435 CM

  • Sanofi-Aventis Investigational Site Number 528006

    Sittard-Geleen, 6162 BG

Other trials in Netherlands

Poland5 sites

  • Sanofi-Aventis Investigational Site Number 616002

    Gdansk, 80-803

  • Sanofi-Aventis Investigational Site Number 616005

    Lodz, 90-549

  • Sanofi-Aventis Investigational Site Number 616001

    Lublin, 20-718

  • Sanofi-Aventis Investigational Site Number 616004

    Szczecin, 70-215

  • Sanofi-Aventis Investigational Site Number 616003

    Warsaw, 04-141

Other trials in Poland

Spain5 sites

  • Sanofi-Aventis Investigational Site Number 724001

    Barcelona, 08035

  • Sanofi-Aventis Investigational Site Number 724007

    Getafe, 28905

  • Sanofi-Aventis Investigational Site Number 724002

    Girona, 17007

  • Sanofi-Aventis Investigational Site Number 724004

    Madrid, 28040

  • Sanofi-Aventis Investigational Site Number 724003

    Seville, 41071

Other trials in Spain

United Kingdom5 sites

  • Sanofi-Aventis Investigational Site Number 826002

    Edinburgh, EH4 2XU

  • Sanofi-Aventis Investigational Site Number 826004

    Haywards Heath, RH16 4EX

  • Sanofi-Aventis Investigational Site Number 826001

    Irvine, KA12 8SS

  • Sanofi-Aventis Investigational Site Number 826003

    Leeds, LS1 3EX

  • Sanofi-Aventis Investigational Site Number 826005

    Salford, M6 8HD

Other trials in United Kingdom

Belgium4 sites

  • Sanofi-Aventis Investigational Site Number 056004

    Bruges, 8000

  • Sanofi-Aventis Investigational Site Number 056002

    Leuven, 3000

  • Sanofi-Aventis Investigational Site Number 056001

    Melsbroek

  • Sanofi-Aventis Investigational Site Number 056003

    Sijsele-Damme

Other trials in Belgium

Philippines4 sites

  • Sanofi-Aventis Investigational Site Number 608004

    Cebu City

  • Sanofi-Aventis Investigational Site Number 608002

    Makati City, 1229

  • Sanofi-Aventis Investigational Site Number 608001

    Manila

  • Sanofi-Aventis Investigational Site Number 608003

    Quezon City, 1102

Other trials in Philippines

Romania4 sites

  • Sanofi-Aventis Investigational Site Number 642006

    Bacau, 600114

  • Sanofi-Aventis Investigational Site Number 642005

    Brasov, 500123

  • Sanofi-Aventis Investigational Site Number 642001

    Bucharest, 010584

  • Sanofi-Aventis Investigational Site Number 642007

    Oradea, 410154

Other trials in Romania

Slovakia4 sites

  • Sanofi-Aventis Investigational Site Number 703003

    Bratislava, 82606

  • Sanofi-Aventis Investigational Site Number 703005

    Bratislava, 82606

  • Sanofi-Aventis Investigational Site Number 703001

    Martin, 03659

  • Sanofi-Aventis Investigational Site Number 703006

    Prešov, 08181

Other trials in Slovakia

Tunisia4 sites

  • Sanofi-Aventis Investigational Site Number 788003

    Manouba, 2010

  • Sanofi-Aventis Investigational Site Number 788004

    Sfax, 3029

  • Sanofi-Aventis Investigational Site Number 788002

    Tunis, 1006

  • Sanofi-Aventis Investigational Site Number 788001

    Tunis, 1007

Other trials in Tunisia

Chile3 sites

  • Sanofi-Aventis Investigational Site Number 152006

    Santiago

  • Sanofi-Aventis Investigational Site Number 152007

    Santiago

  • Sanofi-Aventis Investigational Site Number 152002

    Viña del Mar

Other trials in Chile

Czechia3 sites

  • Sanofi-Aventis Investigational Site Number 203001

    Brno, 65691

  • Sanofi-Aventis Investigational Site Number 203002

    Ostrava - Poruba, 70852

  • Sanofi-Aventis Investigational Site Number 203004

    Teplice, 415 29

Other trials in Czechia

Sweden3 sites

  • Sanofi-Aventis Investigational Site Number 752002

    Stockholm, 141 86

  • Sanofi-Aventis Investigational Site Number 752001

    Stockholm, 171 76

  • Sanofi-Aventis Investigational Site Number 752003

    Stockholm, 182 88

Other trials in Sweden

Estonia2 sites

  • Sanofi-Aventis Investigational Site Number 233002

    Tallinn, 10617

  • Sanofi-Aventis Investigational Site Number 233001

    Tartu, 50406

Other trials in Estonia

Greece2 sites

  • Sanofi-Aventis Investigational Site Number 300001

    Athens, 11527

  • Sanofi-Aventis Investigational Site Number 300006

    Thessaloniki, 57010

Other trials in Greece

Mexico2 sites

  • Sanofi-Aventis Investigational Site Number 484003

    México, 06726

  • Sanofi-Aventis Investigational Site Number 484005

    Monterrey, 64460

Other trials in Mexico

Thailand2 sites

  • Sanofi-Aventis Investigational Site Number 764001

    Bangkok, 10330

  • Sanofi-Aventis Investigational Site Number 764002

    Bangkok Noi, 10700

Other trials in Thailand

Austria1 site

  • Sanofi-Aventis Investigational Site Number 040001

    Vienna, 1010

Other trials in Austria

About this study

Official title: A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis

The primary objective of the study was to assess the effect of two doses of teriflunomide, in comparison to placebo, on the frequency of multiple sclerosis (MS) relapses in participants with relapsing MS.

Key secondary objective was to assess the effect of the two doses of teriflunomide, in comparison to placebo, on disability progression.

Other secondary objectives were:

  • To assess the effect of the two doses of teriflunomide in comparison to placebo on:
  • Fatigue;
  • Health-related quality of life, a measure of the impact of the participant's health on his or her overall well being.
  • To evaluate the safety and tolerability of teriflunomide.
Read the detailed description

The study consists of:

  • A core treatment period: Teriflunomide 7 mg or Teriflunomide 14 mg or placebo was administered in double-blind fashion until a fixed common end date which was approximately 48 weeks after randomization of the last participant.
  • An extension treatment period: the highest dose of teriflunomide was administered in open-label fashion to participants who successfully complete the core treatment period and wish to continue.

The overall treatment period was followed by a 4-week elimination follow-up period.

Being tested
Placebo, Teriflunomide
Keywords
relapsing multiple sclerosis
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Film-coated tablet

    Oral administration

  • TeriflunomideDrug

    Also called HMR1726

    Film-coated tablet

    Oral administration

Study groups in NCT00751881
Study groupRoleWhat they receive
Teriflunomide 7 mg / 14 mgExperimentalCore treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Receives: Drug: Teriflunomide
Teriflunomide 14 mg / 14 mgExperimentalCore treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Receives: Drug: Teriflunomide
Placebo / Teriflunomide 14 mgPlacebo comparatorCore treatment period: Placebo (for teriflunomide) once daily. Extension treatment period: Teriflunomide 14 mg once daily.
Receives: Drug: Placebo; Drug: Teriflunomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Core Treatment Period: Annualized Relapse Rate (ARR): Poisson Regression Estimate

    ARR is obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of treatment durations.

    Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores.

    To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).

    Measured: Core treatment period between 48 - 152 weeks depending on time of enrollment

Secondary outcomes (11)

  1. Core Treatment Period: Time to Disability Progression

    Probability of disability progression at 24, 48, 108 and 132 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first 12-week sustained disability progression [i.e. increase from baseline of at least 1 point in EDSS score (at least 0.5 point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks].

    Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation.

    Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.

    Measured: Core treatment period between 48 - 152 weeks depending on time of enrollment

  2. Core Treatment Period: Time Without Relapse

    Probability of no relapse at 24, 48, 108 and 132 weeks was estimated using Kaplan-Meier method on the time to relapse defined as the time from randomization to first EDSS confirmed relapse.

    Participants free of confirmed relapse (no EDSS confirmed relapse observed on treatment) were censored at the date of the last study drug intake.

    Measured: Core treatment period between 48 - 152 weeks depending on time of enrollment

  3. Core Treatment Period: Change From Baseline to Week 48 in EDSS Total Score

    EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation.

    EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).

    Baseline adjusted least-squares means at Week 48 were estimated using a Mixed-effect model with repeated measures (MMRM) on EDSS score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.

    Measured: Baseline (before randomization), Week 12, Week 24, Week 36 and Week 48

  4. Core Treatment Period: Change From Baseline to Week 48 in Fatigue Impact Scale (FIS) Total Score

    FIS is a participants-reported scale that qualifies the impact of fatigue on daily life in participants with MS. It consists of 40 statements that measure fatigue in 3 areas; physical, cognitive, and social.

    FIS total score ranges from 0 (no problem) to 160 (extreme problem).

    Baseline adjusted least-squares means at week 48 were estimated using a Mixed-effect model with repeated measures (MMRM) on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.

    Measured: Baseline (before randomization), Week 12, Week 24 and Week 48

  5. Core Treatment Period: Change From Baseline to Last Visit in Fatigue Impact Scale (FIS) Total Score

    Baseline adjusted least-squares means at last visit were estimated using an analysis of covariance (ANCOVA) model on collected data for FIS total score (treatment group, region of enrollment, baseline EDSS stratum, visit number for the last visit and baseline value as factors).

    Measured: Baseline (before randomization) and up to Week 152

  6. Core Treatment Period: Change From Baseline to Week 48 in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores

    SF-36 scale is a generic, self-administered, health-related quality-of-life (QOL) instrument. It is constructed such that the 36 questions represent 8 of the most important health concepts: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.

    Two summary scores are obtained:

    • the physical health component summary score,
    • the mental health component summary score.

    Both scores range from 0 to 100 and a high score indicates a more favorable health state.

    Baseline adjusted least-squares means at week 48 were estimated using a Mixed-effect model with repeated measures [MMRM] on each summary score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.

    Measured: Baseline (before randomization), Week 12, Week 24 and Week 48

  7. Core Treatment Period: Change From Baseline to Last Visit in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores

    Baseline adjusted least-squares means at last visit were estimated using an analysis of covariance (ANCOVA) model on collected data for each summary score (treatment group, region of enrollment, baseline EDSS stratum, visit number for the last visit and baseline value as factors).

    Measured: Baseline (before randomization) and up to Week 152

  8. Core Treatment Period: Overview of Adverse Events

    Adverse Events (AE) are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

    Measured: From first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first

  9. Extension Treatment Period: Overview of Treatment Emergent Adverse Events (TEAE)

    AEs were any unfavourable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.

    Measured: From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period

  10. Extension Treatment Period: Time to Disability Progression

    Probability of disability progression since the randomization of the core period was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first 12 week sustained disability progression [i.e. increase from baseline of at least 1 point in EDSS score (at least 0.5 point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks].

    Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation.

    Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time ≤t by any earlier computed probabilities to estimate the probability of being event free for the amount of time t. Probability of event at time t was 1 minus the probability of being event-free for the amount of time t.

    Measured: Core treatment period (maximum: 173 weeks) and Extension treatment period (maximum: 174 weeks)

  11. Extension Treatment Period: ARR: Poisson Regression Estimate

    ARR was obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of treatment durations. A relapse is defined as the appearance of a new clinical sign/symptom or clinical worsening of a previous sign/symptom (one that had been stable for at least 30 days) that persists for a minimum of 24 hours in the absence of fever. Relapse was confirmed by an increase in EDSS score or Functional System scores. To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrolment and baseline EDSS stratum as covariates).

    Measured: Extension treatment period (Maximum: 174 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Sep 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionApr 2012
  4. Study completionAug 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
1,169 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00751881
Sponsor's protocol ID
EFC10531
Other IDs
2007-004452-36
Acronym
TOWER
Status last verified
May 2016
First submitted
7 May 2008
Last updated
7 Jul 2016
Data monitoring committee
Yes

Publications

  • Confavreux C, O'Connor P, Comi G, Freedman MS, Miller AE, Olsson TP, Wolinsky JS, Bagulho T, Delhay JL, Dukovic D, Truffinet P, Kappos L; TOWER Trial Group. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014 Mar;13(3):247-56. doi: 10.1016/S1474-4422(13)70308-9. Epub 2014 Jan 23.

    PubMed 24461574

  • Comi G, Freedman MS, Meca-Lallana JE, Vermersch P, Kim BJ, Parajeles A, Edwards KR, Gold R, Korideck H, Chavin J, Poole EM, Coyle PK. Prior treatment status: impact on the efficacy and safety of teriflunomide in multiple sclerosis. BMC Neurol. 2020 Oct 6;20(1):364. doi: 10.1186/s12883-020-01937-4.

    PubMed 33023488

  • Miller AE, Olsson TP, Wolinsky JS, Comi G, Kappos L, Hu X, Xu X, Lublin AL, Truffinet P, Chavin J, Delhay JL, Benamor M, Purvis A, Freedman MS; TOWER investigators. Long-term safety and efficacy of teriflunomide in patients with relapsing multiple sclerosis: Results from the TOWER extension study. Mult Scler Relat Disord. 2020 Nov;46:102438. doi: 10.1016/j.msard.2020.102438. Epub 2020 Aug 1.

    PubMed 32911306

  • Qiu W, Huang DH, Hou SF, Zhang MN, Jin T, Dong HQ, Peng H, Zhang CD, Zhao G, Huang YN, Zhou D, Wu WP, Wang BJ, Li JM, Zhang XH, Cheng Y, Li HF, Li L, Lu CZ, Zhang X, Bu BT, Dong WL, Fan DS, Hu XQ, Xu XH; TOWER Trial Chinese Group. Efficacy and Safety of Teriflunomide in Chinese Patients with Relapsing Forms of Multiple Sclerosis: A Subgroup Analysis of the Phase 3 TOWER Study. Chin Med J (Engl). 2018 Dec 5;131(23):2776-2784. doi: 10.4103/0366-6999.246067.

    PubMed 30511679

  • Freedman MS, Morawski J, Thangavelu K. Clinical efficacy of teriflunomide over a fixed 2-year duration in the TOWER study. Mult Scler J Exp Transl Clin. 2018 May 16;4(2):2055217318775236. doi: 10.1177/2055217318775236. eCollection 2018 Apr-Jun.

    PubMed 29796289

  • Freedman MS, Wolinsky JS, Comi G, Kappos L, Olsson TP, Miller AE, Thangavelu K, Benamor M, Truffinet P, O'Connor PW; TEMSO and TOWER Study Groups. The efficacy of teriflunomide in patients who received prior disease-modifying treatments: Subgroup analyses of the teriflunomide phase 3 TEMSO and TOWER studies. Mult Scler. 2018 Apr;24(4):535-539. doi: 10.1177/1352458517695468. Epub 2017 Mar 17.

    PubMed 28304217

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Teriflunomide in people with Multiple Sclerosis, run by Sanofi at 193 sites in 26 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 193 sites in United States, China, Ukraine, Turkey (Türkiye), Germany and 21 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Jun 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Core Treatment Period: Annualized Relapse Rate (ARR): Poisson Regression Estimate (time frame: Core treatment period between 48 - 152 weeks depending on time of enrollment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00751881, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jul 2016.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in