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

NCT00803049 | Completed Phase 3 Results DMC

• 2 other identifiers: LTS60502006-003361-14
• Study Type: interventional
• Target: 742
• Locations: 21 countries
• Sites: 116

Brief 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.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Oral treatment

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (5)

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

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

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

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

• Percentage of Participants Free of Sustained Disability Progression (DP)

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

• Annualized MS Relapse Rate (ARR): Poisson Regression Estimates

  Up to 8 years since LTS6050 randomization

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

  Baseline, Week 192

Study Arms (4)

Placebo/Teriflunomide 7 mg

EXPERIMENTAL

Participants 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.

Drug: Teriflunomide (HMR1726)

Teriflunomide 7 mg/7 mg

EXPERIMENTAL

Participants 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.

Drug: Teriflunomide (HMR1726)

Placebo/Teriflunomide 14 mg

EXPERIMENTAL

Participants 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.

Drug: Teriflunomide (HMR1726)

Teriflunomide 14 mg/14 mg

EXPERIMENTAL

Participants 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.

Drug: Teriflunomide (HMR1726)

Interventions

Teriflunomide (HMR1726) DRUG

Tablet, oral administration QD.

Also known as: Aubagio

Placebo/Teriflunomide 14 mg; Placebo/Teriflunomide 7 mg; Teriflunomide 14 mg/14 mg; Teriflunomide 7 mg/7 mg

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (116)

Investigational Site Number 1032

Maitland, Florida, 32761, United States

Location

Investigational Site Number 1038

Fort Wayne, Indiana, 63104, United States

Location

Investigational Site Number 1033

Detroit, Michigan, 48201, United States

Location

Investigational Site Number 1037

Allentown, Pennsylvania, 18103, United States

Location

Investigational Site Number 1603

Graz, 8036, Austria

Location

Investigational Site Number 1604

Innsbruck, 6020, Austria

Location

Investigational Site Number 1601

Vienna, 1010, Austria

Location

Investigational Site Number 1602

Vienna, 1090, Austria

Location

Investigational Site Number 1208

Calgary, T2N 2T9, Canada

Location

Investigational Site Number 1212

Gatineau, J9J 0A5, Canada

Location

Investigational Site Number 1205

Greenfield Park, J4V 2J2, Canada

Location

Investigational Site Number 1201

Halifax, B3H 1V7, Canada

Location

Investigational Site Number 1206

London, N6A 5A5, Canada

Location

Investigational Site Number 1203

Montreal, H2L 4M1, Canada

Location

Investigational Site Number 1204

Ottawa, K1H 8L6, Canada

Location

Investigational Site Number 1202

Québec, G1J 1Z4, Canada

Location

Investigational Site Number 1211

St. John's, A1B 3V6, Canada

Location

Investigational Site Number 1209

Toronto, M5B 1W8, Canada

Location

Investigational Site Number 1210

Vancouver, V6T 2B5, Canada

Location

Investigational Site Number 1207

Winnipeg, R3A 1R9, Canada

Location

Investigational Site Number 3804

Santiago, 750-0710, Chile

Location

Investigational Site Number 3802

Santiago, 760-0746, Chile

Location

Investigational Site Number 3803

Santiago, 890-0085, Chile

Location

Investigational Site Number 3801

Santiago, Chile

Location

Investigational Site Number 3805

Viña del Mar, Chile

Location

Investigational Site Number 4101

Olomouc, 77520, Czechia

Location

Investigational Site Number 4801

Glostrup Municipality, 2600, Denmark

Location

Investigational Site Number 4804

Sønderborg, 6400, Denmark

Location

Investigational Site Number 4802

Vejle, 7100, Denmark

Location

Investigational Site Number 1502

Tallinn, 10617, Estonia

Location

Investigational Site Number 1501

Tartu, 50406, Estonia

Location

Investigational Site Number 2203

Helsinki, 00100, Finland

Location

Investigational Site Number 2206

Pori, 28100, Finland

Location

Investigational Site Number 2201

Tampere, 33100, Finland

Location

Investigational Site Number 2202

Turku, 20520, Finland

Location

Investigational Site Number 2415

Besançon, 25030, France

Location

Investigational Site Number 2403

Clermont-Ferrand, 63003, France

Location

Investigational Site Number 2408

Dijon, 21079, France

Location

Investigational Site Number 2413

Lille, 59020, France

Location

Investigational Site Number 2404

Limoges, 87042, France

Location

Investigational Site Number 2401

Lyon, 69394, France

Location

Investigational Site Number 2409

Marseille, 13005, France

Location

Investigational Site Number 2402

Montpellier, 34000, France

Location

Investigational Site Number 2405

Nancy, 54036, France

Location

Investigational Site Number 2414

Nantes, 44093, France

Location

Investigational Site Number 2407

Nice, 06002, France

Location

Investigational Site Number 2410

Paris, 75571, France

Location

Investigational Site Number 2406

Rennes, 35033, France

Location

Investigational Site Number 2411

Toulouse, 31059, France

Location

Investigational Site Number 2011

Berlin, 10785, Germany

Location

Investigational Site Number 2001

Berlin, 13347, Germany

Location

Investigational Site Number 2000

Bochum, 44791, Germany

Location

Investigational Site Number 2012

Erbach im Odenwald, 64711, Germany

Location

Investigational Site Number 2004

Essen, 45122, Germany

Location

Investigational Site Number 2005

Giessen, 35385, Germany

Location

Investigational Site Number 2007

Hanover, 30625, Germany

Location

Investigational Site Number 2008

Münster, 48149, Germany

Location

Investigational Site Number 2010

Offenbach, 63069, Germany

Location

Investigational Site Number 2009

Rostock, 18055, Germany

Location

Investigational Site Number 2003

Wiesbaden, 65191, Germany

Location

Investigational Site Number 2819

Bari, 70124, Italy

Location

Investigational Site Number 2827

Fidenza, 43036, Italy

Location

Investigational Site Number 2803

Florence, 50134, Italy

Location

Investigational Site Number 2814

Gallarate, 21013, Italy

Location

Investigational Site Number 2808

Milan, 20132, Italy

Location

Investigational Site Number 2812

Padua, 35128, Italy

Location

Investigational Site Number 2809

Pavia, 27100, Italy

Location

Investigational Site Number 2813

Roma, 00152, Italy

Location

Investigational Site Number 2824

Roma, 00185, Italy

Location

Investigational Site Number 4602

's-Hertogenbosch, 5223 GZ, Netherlands

Location

Investigational Site Number 4605

Breda, 4818 CK, Netherlands

Location

Investigational Site Number 4601

Nijmegen, 6525 GC, Netherlands

Location

Investigational Site Number 4604

Sittard-Geleen, 6162 BG, Netherlands

Location

Investigational Site Number 3601

Oslo, 0407, Norway

Location

Investigational Site Number 3604

Tønsberg, 3116, Norway

Location

Investigational Site Number 3008

Bialystok, 15-276, Poland

Location

Investigational Site Number 3009

Bialystok, 15-402, Poland

Location

Investigational Site Number 3007

Gdansk, 80-803, Poland

Location

Investigational Site Number 3005

Lodz, 90-153, Poland

Location

Investigational Site Number 3006

Lublin, 20-718, Poland

Location

Investigational Site Number 3004

Lublin, 20-954, Poland

Location

Investigational Site Number 3001

Poznan, 60-355, Poland

Location

Investigational Site Number 3002

Warsaw, 02-097, Poland

Location

Investigational Site Number 3003

Warsaw, 02-957, Poland

Location

Investigational Site Number 4201

Coimbra, 3000-075, Portugal

Location

Investigational Site Number 4203

Lisbon, 1169-050, Portugal

Location

Investigational Site Number 3203

Moscow, 119049, Russia

Location

Investigational Site Number 3205

Moscow, 125015, Russia

Location

Investigational Site Number 3207

Nizhny Novgorod, 603076, Russia

Location

Investigational Site Number 3208

Novosibirsk, 630087, Russia

Location

Investigational Site Number 3201

Saint Petersburg, 194044, Russia

Location

Investigational Site Number 3202

Saint Petersburg, 197089, Russia

Location

Investigational Site Number 3206

Saint Petersburg, 197376, Russia

Location

Investigational Site Number 3401

Stockholm, 171 76, Sweden

Location

Investigational Site Number 1802

Basel, 4031, Switzerland

Location

Investigational Site Number 5003

Izmir, 35340, Turkey (Türkiye)

Location

Investigational Site Number 5006

Izmir, 35380, Turkey (Türkiye)

Location

Investigational Site Number 5005

Kocaeli, 41380, Turkey (Türkiye)

Location

Investigational Site Number 5001

Sihhiye / Ankara, 06100, Turkey (Türkiye)

Location

Investigational Site Number 3504

Dnipropetrovsk, 49027, Ukraine

Location

Investigational Site Number 3505

Ivano-Frankivsk, 76008, Ukraine

Location

Investigational Site Number 3506

Kharkiv, 61018, Ukraine

Location

Investigational Site Number 3510

Kharkiv, 61178, Ukraine

Location

Investigational Site Number 3508

Lviv, 79010, Ukraine

Location

Investigational Site Number 3502

Odesa, 65025, Ukraine

Location

Investigational Site Number 3509

Uzhhorod, 88018, Ukraine

Location

Investigational Site Number 3507

Vinnitsa, 21005, Ukraine

Location

Investigational Site Number 3501

Zaporizhzhya, 69600, Ukraine

Location

Investigational Site Number 2604

Dundee, DD1 9SY, United Kingdom

Location

Investigational Site Number 2607

London, E1 1BB, United Kingdom

Location

Investigational Site Number 2608

London, SW17 0QT, United Kingdom

Location

Investigational Site Number 2600

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Investigational Site Number 2601

Nottingham, NG7 2UH, United Kingdom

Location

Investigational Site Number 2609

Plymouth, PL6 8BX, United Kingdom

Location

Investigational Site Number 2606

Sheffield, S10 2JF, United Kingdom

Location

Investigational Site Number 2602

Stoke-on-Trent, ST4 7LN, United Kingdom

Location

Related Publications (4)

• 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.

  PMID: 35485424 DERIVED

• 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.

  PMID: 33023488 DERIVED

• 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.

  PMID: 31198103 DERIVED

• 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.

  PMID: 28680917 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2008
• First Posted: December 5, 2008
• Study Start: October 1, 2006
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: January 30, 2017
• Results First Posted: January 30, 2017

Record last verified: 2016-12

Locations

NO (2); ES (2); CH (1); FR (14); IT (9); GB (8); AU (4); CL (5); CA (12); CZ (1); NL (4); RU (7); US (4); PT (2); TU (4); UA (9); PL (9); DK (3); FI (4); SE (1); DE (11)