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Multiple SclerosisPhase 3NCT00803049

Long Term Safety and Efficacy Study of Teriflunomide 7 mg or 14 mg in Patients With Relapsing-Remitting Multiple Sclerosis

A Phase 3 study testing Teriflunomide (HMR1726) in people with Multiple Sclerosis, run by Sanofi at 116 sites in 21 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 this study was to document the long-term safety and tolerability of teriflunomide in Multiple Sclerosis (MS) participants with relapse. The secondary objective was to document the long-term efficacy on disability progression, relapse rate and Magnetic Resonance Imaging (MRI) parameters. 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 (HMR1726)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
742 participants
Where
116 sitesin 21 countries
Study dates
Oct 2006to Dec 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

  • Participant who completed the previous double-blind placebo-controlled study EFC6049 and who did not meet criteria for treatment withdrawal.
  • Willingness to participate in a long-term safety/efficacy trial.

Who cannot join

  • 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

116 sites in 21 countries.

116 sites in 21 countries

France14 sites

  • Investigational Site Number 2415

    Besançon, 25030

  • Investigational Site Number 2403

    Clermont-Ferrand, 63003

  • Investigational Site Number 2408

    Dijon, 21079

  • Investigational Site Number 2413

    Lille, 59020

  • Investigational Site Number 2404

    Limoges, 87042

  • Investigational Site Number 2401

    Lyon, 69394

  • Investigational Site Number 2409

    Marseille, 13005

  • Investigational Site Number 2402

    Montpellier, 34000

  • Investigational Site Number 2405

    Nancy, 54036

  • Investigational Site Number 2414

    Nantes, 44093

  • Investigational Site Number 2407

    Nice, 06002

  • Investigational Site Number 2410

    Paris, 75571

  • Investigational Site Number 2406

    Rennes, 35033

  • Investigational Site Number 2411

    Toulouse, 31059

Other trials in France

Canada12 sites

  • Investigational Site Number 1208

    Calgary, T2N 2T9

  • Investigational Site Number 1212

    Gatineau, J9J 0A5

  • Investigational Site Number 1205

    Greenfield Park, J4V 2J2

  • Investigational Site Number 1201

    Halifax, B3H 1V7

  • Investigational Site Number 1206

    London, N6A 5A5

  • Investigational Site Number 1203

    Montreal, H2L 4M1

  • Investigational Site Number 1204

    Ottawa, K1H 8L6

  • Investigational Site Number 1202

    Québec, G1J 1Z4

  • Investigational Site Number 1211

    St. John's, A1B 3V6

  • Investigational Site Number 1209

    Toronto, M5B 1W8

  • Investigational Site Number 1210

    Vancouver, V6T 2B5

  • Investigational Site Number 1207

    Winnipeg, R3A 1R9

Other trials in Canada

Germany11 sites

  • Investigational Site Number 2011

    Berlin, 10785

  • Investigational Site Number 2001

    Berlin, 13347

  • Investigational Site Number 2000

    Bochum, 44791

  • Investigational Site Number 2012

    Erbach im Odenwald, 64711

  • Investigational Site Number 2004

    Essen, 45122

  • Investigational Site Number 2005

    Giessen, 35385

  • Investigational Site Number 2007

    Hanover, 30625

  • Investigational Site Number 2008

    Münster, 48149

  • Investigational Site Number 2010

    Offenbach, 63069

  • Investigational Site Number 2009

    Rostock, 18055

  • Investigational Site Number 2003

    Wiesbaden, 65191

Other trials in Germany

Italy9 sites

  • Investigational Site Number 2819

    Bari, 70124

  • Investigational Site Number 2827

    Fidenza, 43036

  • Investigational Site Number 2803

    Florence, 50134

  • Investigational Site Number 2814

    Gallarate, 21013

  • Investigational Site Number 2808

    Milan, 20132

  • Investigational Site Number 2812

    Padova, 35128

  • Investigational Site Number 2809

    Pavia, 27100

  • Investigational Site Number 2813

    Roma, 00152

  • Investigational Site Number 2824

    Roma, 00185

Other trials in Italy

Poland9 sites

  • Investigational Site Number 3008

    Bialystok, 15-276

  • Investigational Site Number 3009

    Bialystok, 15-402

  • Investigational Site Number 3007

    Gdansk, 80-803

  • Investigational Site Number 3005

    Lodz, 90-153

  • Investigational Site Number 3006

    Lublin, 20-718

  • Investigational Site Number 3004

    Lublin, 20-954

  • Investigational Site Number 3001

    Poznan, 60-355

  • Investigational Site Number 3002

    Warsaw, 02-097

  • Investigational Site Number 3003

    Warsaw, 02-957

Other trials in Poland

Ukraine9 sites

  • Investigational Site Number 3504

    Dnipropetrovsk, 49027

  • Investigational Site Number 3505

    Ivano-Frankivsk, 76008

  • Investigational Site Number 3506

    Kharkiv, 61018

  • Investigational Site Number 3510

    Kharkiv, 61178

  • Investigational Site Number 3508

    Lviv, 79010

  • Investigational Site Number 3502

    Odesa, 65025

  • Investigational Site Number 3509

    Uzhhorod, 88018

  • Investigational Site Number 3507

    Vinnitsa, 21005

  • Investigational Site Number 3501

    Zaporizhzhya, 69600

Other trials in Ukraine

United Kingdom8 sites

  • Investigational Site Number 2604

    Dundee, DD1 9SY

  • Investigational Site Number 2607

    London, E1 1BB

  • Investigational Site Number 2608

    London, SW17 0QT

  • Investigational Site Number 2600

    Newcastle upon Tyne, NE1 4LP

  • Investigational Site Number 2601

    Nottingham, NG7 2UH

  • Investigational Site Number 2609

    Plymouth, PL6 8BX

  • Investigational Site Number 2606

    Sheffield, S10 2JF

  • Investigational Site Number 2602

    Stoke-on-Trent, ST4 7LN

Other trials in United Kingdom

Russia7 sites

  • Investigational Site Number 3203

    Moscow, 119049

  • Investigational Site Number 3205

    Moscow, 125015

  • Investigational Site Number 3207

    Nizhny Novgorod, 603076

  • Investigational Site Number 3208

    Novosibirsk, 630087

  • Investigational Site Number 3201

    Saint Petersburg, 194044

  • Investigational Site Number 3202

    Saint Petersburg, 197089

  • Investigational Site Number 3206

    Saint Petersburg, 197376

Other trials in Russia

Chile5 sites

  • Investigational Site Number 3804

    Santiago, 750-0710

  • Investigational Site Number 3802

    Santiago, 760-0746

  • Investigational Site Number 3803

    Santiago, 890-0085

  • Investigational Site Number 3801

    Santiago

  • Investigational Site Number 3805

    Viña del Mar

Other trials in Chile

United States4 sites

  • Investigational Site Number 1037

    Allentown, Pennsylvania, 18103

  • Investigational Site Number 1033

    Detroit, Michigan, 48201

  • Investigational Site Number 1038

    Fort Wayne, Indiana, 63104

  • Investigational Site Number 1032

    Maitland, Florida, 32761

Other trials in United States

Austria4 sites

  • Investigational Site Number 1603

    Graz, 8036

  • Investigational Site Number 1604

    Innsbruck, 6020

  • Investigational Site Number 1601

    Vienna, 1010

  • Investigational Site Number 1602

    Vienna, 1090

Other trials in Austria

Finland4 sites

  • Investigational Site Number 2203

    Helsinki, 00100

  • Investigational Site Number 2206

    Pori, 28100

  • Investigational Site Number 2201

    Tampere, 33100

  • Investigational Site Number 2202

    Turku, 20520

Other trials in Finland

Netherlands4 sites

  • Investigational Site Number 4602

    's-Hertogenbosch, 5223 GZ

  • Investigational Site Number 4605

    Breda, 4818 CK

  • Investigational Site Number 4601

    Nijmegen, 6525 GC

  • Investigational Site Number 4604

    Sittard-Geleen, 6162 BG

Other trials in Netherlands

Turkey (Türkiye)4 sites

  • Investigational Site Number 5003

    Izmir, 35340

  • Investigational Site Number 5006

    Izmir, 35380

  • Investigational Site Number 5005

    Kocaeli, 41380

  • Investigational Site Number 5001

    Sihhiye / Ankara, 06100

Other trials in Turkey (Türkiye)

Denmark3 sites

  • Investigational Site Number 4801

    Glostrup Municipality, 2600

  • Investigational Site Number 4804

    Sønderborg, 6400

  • Investigational Site Number 4802

    Vejle, 7100

Other trials in Denmark

Estonia2 sites

  • Investigational Site Number 1502

    Tallinn, 10617

  • Investigational Site Number 1501

    Tartu, 50406

Other trials in Estonia

Norway2 sites

  • Investigational Site Number 3601

    Oslo, 0407

  • Investigational Site Number 3604

    Tønsberg, 3116

Other trials in Norway

Portugal2 sites

  • Investigational Site Number 4201

    Coimbra, 3000-075

  • Investigational Site Number 4203

    Lisbon, 1169-050

Other trials in Portugal

Czechia1 site

  • Investigational Site Number 4101

    Olomouc, 77520

Other trials in Czechia

Sweden1 site

  • Investigational Site Number 3401

    Stockholm, 171 76

Other trials in Sweden

Switzerland1 site

  • Investigational Site Number 1802

    Basel, 4031

Other trials in Switzerland

About this study

Official title: Long-term Extension of the Multinational, Double-blind, Placebo Controlled Study EFC6049 (HMR1726D/3001) to Document the Safety of Two Doses of Teriflunomide (7 and 14 mg) in Patients With Multiple Sclerosis With Relapses

The primary objective of this study was to document the long-term safety and tolerability of teriflunomide in Multiple Sclerosis (MS) participants with relapse.

The secondary objective was to document the long-term efficacy on disability progression, relapse rate and Magnetic Resonance Imaging (MRI) parameters.

Read the detailed description

Participants completing the EFC6049 (HMR1726D/3001) study were given the opportunity to continue in the extension study;

  • participants receiving teriflunomide 7 mg or 14 mg were blindly maintained on the same dose of teriflunomide.
  • participants receiving placebo were randomized at a 1:1 ratio to teriflunomide 7 mg or 14 mg.

The study period per participant was broken down as follows:

  • Double-blind treatment: up to a maximum of 288 weeks or until teriflunomide was commercially available in the country where participant lived,
  • Post-washout follow-up: 4 weeks after last treatment intake. No post-washout follow up if participant continued on teriflunomide treatment by obtaining its commercial form after end of the study.

The total duration of the extension was 292 weeks (about 6 years) from the first participant enrolled or until teriflunomide is commercially available in the country where participant lived.

Being tested
Teriflunomide (HMR1726)
Keywords
Multiple Sclerosis, Oral treatment
Medical subject headings
Multiple Sclerosis

What participants receive

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

  • Teriflunomide (HMR1726)Drug

    Also called Aubagio

    Tablet, oral administration QD.

Study groups in NCT00803049
Study groupRoleWhat they receive
Placebo/Teriflunomide 7 mgExperimentalParticipants who completed treatment of placebo (for teriflunomide) tablet once daily (QD) for 108 weeks in EFC6049 study, received teriflunomide tablet 7 mg QD for 288 weeks in this extension study.
Receives: Drug: Teriflunomide (HMR1726)
Teriflunomide 7 mg/7 mgExperimentalParticipants who completed treatment of teriflunomide 7 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 7 mg tablet QD for 288 weeks in this extension study.
Receives: Drug: Teriflunomide (HMR1726)
Placebo/Teriflunomide 14 mgExperimentalParticipants who completed treatment of placebo (for teriflunomide) tablet QD for 108 weeks in EFC6049, study received teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Receives: Drug: Teriflunomide (HMR1726)
Teriflunomide 14 mg/14 mgExperimentalParticipants who completed treatment of teriflunomide 14 mg tablet QD for 108 weeks in EFC6049 study, continued their treatment with teriflunomide 14 mg tablet QD for 288 weeks in this extension study.
Receives: Drug: Teriflunomide (HMR1726)

What is being measured

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

  1. Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

    Adverse event (AE) was defined as any untoward medical occurrence in a participant who received investigational medicinal product (IMP) without regard to possibility of causal relationship with this treatment. TEAEs: AEs that developed or worsened or became serious during on-treatment period which was defined as the period from the time of first dose of study drug (in LTS6050) up to 4 weeks (28 days) after last dose of study drug. 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 both serious and non-serious AEs.

    Measured: Baseline (LTS6050) up to 28 days after last dose of study drug up to 450 weeks

Secondary outcomes (5)

  1. Time to 12 Week Sustained Disability Progression (DP): Kaplan-Meier Estimates of the Rate of DP

    Sustained DP defined as sustained increase of at least 1 point from baseline (EFC6049) expanded disability status scale (EDSS) score (0.5 point for participants with baseline EDSS>5.5) persisting for at least 12 weeks. EDSS: an ordinal scale qualifies disability in participants with MS. EDSS total score range: 0 (normal neurological examination) to 10 (death due to Multiple Sclerosis [MS]). Probability of DP at 12 weeks was estimated using Kaplan-Meier method on time to DP defined as date of first DP minus (-) date of randomization in EFC6049 study +1 day. Participants free of DP (no DP observed on treatment) were censored at the date of last on-treatment EDSS evaluation in LTS6050. 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.

    Measured: Up to 10.8 years (EFC6049: 108 weeks + LTS6050: 450 weeks)

  2. Time to 24 Week Sustained Disability Progression (DP): Kaplan-Meier Estimates of the Rate of DP

    Sustained DP was defined as sustained increase of at least 1 point from baseline (EFC6049) EDSS score (0.5 point for participants with baseline EDSS>5.5) persisting for at least 24 weeks. EDSS: an ordinal scale qualifies disability in participants with MS. EDSS total score range: 0 (normal neurological examination) to 10 (death due to MS). Probability of DP at 24 weeks was estimated using Kaplan-Meier method on time to DP defined as date of first DP minus (-) date of randomization in EFC6049 study +1 day. Participants free of DP (no DP observed on treatment) were censored at the date of last on-treatment EDSS evaluation in LTS6050. 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.

    Measured: Up to 10.8 years (EFC6049: 108 weeks + LTS6050: 450 weeks)

  3. Percentage of Participants Free of Sustained Disability Progression (DP)

    Sustained DP was defined as sustained increase of at least 1 point from baseline (EFC6049) EDSS score (0.5 point for participants with baseline EDSS>5.5) persisting for at least 12 weeks and 24 weeks. EDSS is an ordinal scale in half-point increments that qualifies disability in participants with MS. It consists of 8 ordinal rating scales assessing seven functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder, cerebral) as well as ambulation. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicates worse neurological function. Percentage of participants who were considered as free of disability progression confirmed after 12 week sustained progression and 24 week sustained progression were reported. Analysis for this outcome measure was performed on combined data of EFC6049 and LTS6050 study, as pre-specified in protocol.

    Measured: Up to 10.8 years since EFC6049 randomization (EFC6049: 108 weeks + LTS6050: 450 weeks)

  4. Annualized MS Relapse Rate (ARR): Poisson Regression Estimates

    ARR was obtained from total number of confirmed relapses that occurred during treatment period divided by sum of treatment durations in LTS6050 study only. 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 EDSS score or Functional System (FS) scores. EDSS: an ordinal scale qualifies disability. EDSS total score range: 0 (normal neurological examination) to 10 (death due to MS). FSS: to assess the neurological function. Total score range: 0 (normal) - 6(worse), higher scores = worse neurological function. To account for the different treatment duration 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: Up to 8 years since LTS6050 randomization

  5. Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Volume of Abnormal Lesions (Burden of Disease [BOD]) at Week 192 Since LTS6050 Randomization

    BOD was assessed by cerebral MRI and defined as the total volume of all abnormal brain tissue (calculated as the sum of the total volume of T2-lesion component and T1-hypointense lesion component).

    Measured: Baseline, Week 192

Timeline

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

  1. First posted5 Dec 2008 (estimated)
  2. Study startOct 2006
  3. Primary completionDec 2015
  4. Study completionDec 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
Double blind
Who is masked
Participant, Investigator
Enrolment
742 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00803049
Sponsor's protocol ID
LTS6050
Other IDs
2006-003361-14
Status last verified
Dec 2016
First submitted
1 Dec 2008
Last updated
30 Jan 2017
Data monitoring committee
Yes

Publications

  • Sprenger T, Kappos L, Sormani MP, Miller AE, Poole EM, Cavalier S, Wuerfel J. Effects of teriflunomide treatment on cognitive performance and brain volume in patients with relapsing multiple sclerosis: Post hoc analysis of the TEMSO core and extension studies. Mult Scler. 2022 Oct;28(11):1719-1728. doi: 10.1177/13524585221089534. Epub 2022 Apr 29.

    PubMed 35485424

  • 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

  • Sprenger T, Kappos L, Radue EW, Gaetano L, Mueller-Lenke N, Wuerfel J, Poole EM, Cavalier S. Association of brain volume loss and long-term disability outcomes in patients with multiple sclerosis treated with teriflunomide. Mult Scler. 2020 Sep;26(10):1207-1216. doi: 10.1177/1352458519855722. Epub 2019 Jun 14.

    PubMed 31198103

  • Sormani MP, Truffinet P, Thangavelu K, Rufi P, Simonson C, De Stefano N. Predicting long-term disability outcomes in patients with MS treated with teriflunomide in TEMSO. Neurol Neuroimmunol Neuroinflamm. 2017 Jun 28;4(5):e379. doi: 10.1212/NXI.0000000000000379. eCollection 2017 Sep.

    PubMed 28680917

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Teriflunomide (HMR1726) in people with Multiple Sclerosis, run by Sanofi at 116 sites in 21 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 2 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 30 Jan 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 116 sites in France, Canada, Germany, Italy, Poland and 16 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. 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 30 Jan 2017). 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?

Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) (time frame: Baseline (LTS6050) up to 28 days after last dose of study drug up to 450 weeks). 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 NCT00803049, which also lists 4 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 30 Jan 2017.

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