Clinical trial NCT00803049: Long Term Safety and Efficacy Study of Teriflunomide 7 mg or 14 mg in Patients With Relapsing-Remitting Multiple Sclerosis
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Oral treatment
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-12-05
Enrollment: 742
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline (LTS6050) up to 28 days after last dose of study drug up to 450 weeks
Secondary outcomes:
measure: Time to 12 Week Sustained Disability Progression (DP): Kaplan-Meier Estimates of the Rate of DP
timeFrame: Up to 10.8 years (EFC6049: 108 weeks + LTS6050: 450 weeks)
measure: Time to 24 Week Sustained Disability Progression (DP): Kaplan-Meier Estimates of the Rate of DP
timeFrame: Up to 10.8 years (EFC6049: 108 weeks + LTS6050: 450 weeks)
measure: Percentage of Participants Free of Sustained Disability Progression (DP)
timeFrame: Up to 10.8 years since EFC6049 randomization (EFC6049: 108 weeks + LTS6050: 450 weeks)
measure: Annualized MS Relapse Rate (ARR): Poisson Regression Estimates
timeFrame: Up to 8 years since LTS6050 randomization
measure: Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Volume of Abnormal Lesions (Burden of Disease [BOD]) at Week 192 Since LTS6050 Randomization
timeFrame: Baseline, Week 192
Other outcomes:
Locations:
city: Maitland
country: United States
facility: Investigational Site Number 1032
state: Florida
city: Ft. Wayne
country: United States
facility: Investigational Site Number 1038
state: Indiana
city: Detroit
country: United States
facility: Investigational Site Number 1033
state: Michigan
city: Allentown
country: United States
facility: Investigational Site Number 1037
state: Pennsylvania
city: Graz
country: Austria
facility: Investigational Site Number 1603
city: Innsbruck
country: Austria
facility: Investigational Site Number 1604
city: Wien
country: Austria
facility: Investigational Site Number 1601
city: Wien
country: Austria
facility: Investigational Site Number 1602
city: Calgary
country: Canada
facility: Investigational Site Number 1208
city: Gatineau
country: Canada
facility: Investigational Site Number 1212
city: Greenfield Park
country: Canada
facility: Investigational Site Number 1205
city: Halifax
country: Canada
facility: Investigational Site Number 1201
city: London
country: Canada
facility: Investigational Site Number 1206
city: Montreal
country: Canada
facility: Investigational Site Number 1203
city: Ottawa
country: Canada
facility: Investigational Site Number 1204
city: Quebec
country: Canada
facility: Investigational Site Number 1202
city: St. John'S
country: Canada
facility: Investigational Site Number 1211
city: Toronto
country: Canada
facility: Investigational Site Number 1209
city: Vancouver
country: Canada
facility: Investigational Site Number 1210
city: Winnipeg
country: Canada
facility: Investigational Site Number 1207
city: Santiago
country: Chile
facility: Investigational Site Number 3804
city: Santiago
country: Chile
facility: Investigational Site Number 3802
city: Santiago
country: Chile
facility: Investigational Site Number 3803
city: Santiago
country: Chile
facility: Investigational Site Number 3801
city: Viña Del Mar
country: Chile
facility: Investigational Site Number 3805
city: Olomouc
country: Czech Republic
facility: Investigational Site Number 4101
city: Glostrup
country: Denmark
facility: Investigational Site Number 4801
city: Sønderborg
country: Denmark
facility: Investigational Site Number 4804
city: Vejle
country: Denmark
facility: Investigational Site Number 4802
city: Tallinn
country: Estonia
facility: Investigational Site Number 1502
city: Tartu
country: Estonia
facility: Investigational Site Number 1501
city: Helsinki
country: Finland
facility: Investigational Site Number 2203
city: Pori
country: Finland
facility: Investigational Site Number 2206
city: Tampere
country: Finland
facility: Investigational Site Number 2201
city: Turku
country: Finland
facility: Investigational Site Number 2202
city: Besancon
country: France
facility: Investigational Site Number 2415
city: Clermont Ferrand Cedex 1
country: France
facility: Investigational Site Number 2403
city: Dijon
country: France
facility: Investigational Site Number 2408
city: Lille Cedex
country: France
facility: Investigational Site Number 2413
city: Limoges Cedex
country: France
facility: Investigational Site Number 2404
city: Lyon Cedex 03
country: France
facility: Investigational Site Number 2401
city: Marseille
country: France
facility: Investigational Site Number 2409
city: Montpellier Cedex 5
country: France
facility: Investigational Site Number 2402
city: Nancy Cedex
country: France
facility: Investigational Site Number 2405
city: Nantes Cedex 01
country: France
facility: Investigational Site Number 2414
city: Nice Cedex
country: France
facility: Investigational Site Number 2407
city: Paris Cedex 12
country: France
facility: Investigational Site Number 2410
city: Rennes Cedex
country: France
facility: Investigational Site Number 2406
city: Toulouse
country: France
facility: Investigational Site Number 2411
city: Berlin
country: Germany
facility: Investigational Site Number 2011
city: Berlin
country: Germany
facility: Investigational Site Number 2001
city: Bochum
country: Germany
facility: Investigational Site Number 2000
city: Erbach
country: Germany
facility: Investigational Site Number 2012
city: Essen
country: Germany
facility: Investigational Site Number 2004
city: Gießen
country: Germany
facility: Investigational Site Number 2005
city: Hannover
country: Germany
facility: Investigational Site Number 2007
city: Münster
country: Germany
facility: Investigational Site Number 2008
city: Offenbach
country: Germany
facility: Investigational Site Number 2010
city: Rostock
country: Germany
facility: Investigational Site Number 2009
city: Wiesbaden
country: Germany
facility: Investigational Site Number 2003
city: Bari
country: Italy
facility: Investigational Site Number 2819
city: Fidenza
country: Italy
facility: Investigational Site Number 2827
city: Firenze
country: Italy
facility: Investigational Site Number 2803
city: Gallarate
country: Italy
facility: Investigational Site Number 2814
city: Milano
country: Italy
facility: Investigational Site Number 2808
city: Padova
country: Italy
facility: Investigational Site Number 2812
city: Pavia
country: Italy
facility: Investigational Site Number 2809
city: Roma
country: Italy
facility: Investigational Site Number 2813
city: Roma
country: Italy
facility: Investigational Site Number 2824
city: 'S Hertogenbosch
country: Netherlands
facility: Investigational Site Number 4602
city: Breda
country: Netherlands
facility: Investigational Site Number 4605
city: Nijmegen
country: Netherlands
facility: Investigational Site Number 4601
city: Sittard-Geleen
country: Netherlands
facility: Investigational Site Number 4604
city: Oslo
country: Norway
facility: Investigational Site Number 3601
city: Tønsberg
country: Norway
facility: Investigational Site Number 3604
city: Bialystok
country: Poland
facility: Investigational Site Number 3008
city: Bialystok
country: Poland
facility: Investigational Site Number 3009
city: Gdansk
country: Poland
facility: Investigational Site Number 3007
city: Lodz
country: Poland
facility: Investigational Site Number 3005
city: Lublin
country: Poland
facility: Investigational Site Number 3006
city: Lublin
country: Poland
facility: Investigational Site Number 3004
city: Poznan
country: Poland
facility: Investigational Site Number 3001
city: Warszawa
country: Poland
facility: Investigational Site Number 3002
city: Warszawa
country: Poland
facility: Investigational Site Number 3003
city: Coimbra
country: Portugal
facility: Investigational Site Number 4201
city: Lisboa
country: Portugal
facility: Investigational Site Number 4203
city: Moscow
country: Russian Federation
facility: Investigational Site Number 3203
city: Moscow
country: Russian Federation
facility: Investigational Site Number 3205
city: Nizhny Novgorod
country: Russian Federation
facility: Investigational Site Number 3207
city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 3208
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 3201
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 3202
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 3206
city: Stockholm
country: Sweden
facility: Investigational Site Number 3401
city: Basel
country: Switzerland
facility: Investigational Site Number 1802
city: Izmir
country: Turkey
facility: Investigational Site Number 5003
city: Izmir
country: Turkey
facility: Investigational Site Number 5006
city: Kocaeli
country: Turkey
facility: Investigational Site Number 5005
city: Sihhiye / Ankara
country: Turkey
facility: Investigational Site Number 5001
city: Dnipropetrovsk
country: Ukraine
facility: Investigational Site Number 3504
city: Ivano-Frankovsk
country: Ukraine
facility: Investigational Site Number 3505
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 3506
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 3510
city: Lviv
country: Ukraine
facility: Investigational Site Number 3508
city: Odessa
country: Ukraine
facility: Investigational Site Number 3502
city: Uzhgorod
country: Ukraine
facility: Investigational Site Number 3509
city: Vinnitsa
country: Ukraine
facility: Investigational Site Number 3507
city: Zaporizhzhya
country: Ukraine
facility: Investigational Site Number 3501
city: Dundee
country: United Kingdom
facility: Investigational Site Number 2604
city: London
country: United Kingdom
facility: Investigational Site Number 2607
city: London
country: United Kingdom
facility: Investigational Site Number 2608
city: Newcastle Upon Tyne
country: United Kingdom
facility: Investigational Site Number 2600
city: Nottingham
country: United Kingdom
facility: Investigational Site Number 2601
city: Plymouth
country: United Kingdom
facility: Investigational Site Number 2609
city: Sheffield
country: United Kingdom
facility: Investigational Site Number 2606
city: Stoke On Trent
country: United Kingdom
facility: Investigational Site Number 2602
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.