Phase III Study With Teriflunomide Versus Placebo in Patients With First Clinical Symptom of Multiple Sclerosis

NCT00622700 | Completed Phase 3 Results DMC

• 3 other identifiers: EFC6260HMR1726D-30052006-001152-12
• Study Type: interventional
• Target: 618
• Locations: 20 countries
• Sites: 127

Brief Summary

The primary objective was to demonstrate the effect of teriflunomide (HMR1726) (14 milligram per day \[mg/day\] and 7 mg/day), in comparison to placebo, for reducing conversion of participants presenting with their first clinical episode consistent with multiple sclerosis (MS) to clinically definite multiple sclerosis (CDMS). The secondary objectives were:

• To demonstrate the effect of teriflunomide, in comparison to placebo, on:
• Reducing conversion to definite multiple sclerosis (DMS)
• Reducing annualized relapse rate (ARR)
• Reducing disease activity/progression as measured by Magnetic Resonance Imaging (MRI)
• Reducing accumulation of disability for at least 12 weeks as measured by the Expanded Disability Status Scale (EDSS)
• Proportion of disability-free participants as assessed by the EDSS
• Reducing participant-reported fatigue
• To evaluate the safety and tolerability of teriflunomide
• To evaluate the pharmacokinetics (PK) of teriflunomide
• Optional pharmacogenomic testing aimed at assessing the association between the main enzyme systems of teriflunomide metabolism and hepatic safety, and other potential associations between gene variations and clinical outcomes

Conditions

Multiple Sclerosis

Keywords

MS; Clinically Isolated Syndrome; CIS; CDMS; relapses

Outcome Measures

Primary Outcomes (1)

• Core Treatment Period: Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS)

  Conversion to CDMS was defined by the occurrence of a relapse, which was defined as a new neurological abnormality separated by at least 30 days from onset of a preceding clinical event, presented for at least 24 hours and occurred in the absence of fever or known infection. Percent probability of conversion at 24, 48, and 108 weeks was estimated using Kaplan-Meier method.

  Up to a maximum of 108 weeks depending on time of enrollment

Secondary Outcomes (14)

• Core Treatment Period: Time to Conversion to Definite Multiple Sclerosis (DMS)

  Up to a maximum of 108 weeks depending on time of enrollment

• Core Treatment Period: Annualized Relapse Rate (ARR)

  Up to a maximum of 108 weeks depending on time of enrollment

• Core Treatment Period: Brain Magnetic Resonance Imaging (MRI) Assessment: Change From Baseline in Total Lesion Volume at Week 108

  Baseline, Week 108

• Core Treatment Period: Brain MRI Assessment: Number of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan (Poisson Regression Estimates)

  Up to a maximum of 108 weeks depending on time of enrollment

• Core Treatment Period: Brain MRI Assessment: Volume of Gadolinium Enhancing (Gd-enhancing) T1-lesions Per MRI Scan

  Up to a maximum of 108 weeks depending on time of enrollment

Other Outcomes (1)

• Core Treatment Period: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)

  From first study drug intake up to 112 days after last intake in the placebo-controlled period or up to first intake in the extension treatment period, whichever occurred first

Study Arms (3)

Placebo/Teriflunomide 7 mg or Teriflunomide 14 mg

PLACEBO COMPARATOR

Core treatment period: Placebo matched to teriflunomide tablet once daily orally. Extension treatment period: Re-randomized in 1:1 ratio to either teriflunomide 7 mg or 14 mg once daily orally.

Drug: Teriflunomide; Drug: Placebo

Teriflunomide 7 mg/7 mg

EXPERIMENTAL

Core treatment period: Teriflunomide 7 mg tablet once daily orally. Extension treatment period: Teriflunomide 7 mg tablet once daily orally.

Drug: Teriflunomide

Teriflunomide 14 mg/14 mg

EXPERIMENTAL

Core treatment period: Teriflunomide 14 mg tablet once daily orally. Extension treatment period: Teriflunomide 14 mg tablet once daily orally.

Drug: Teriflunomide

Interventions

Teriflunomide DRUG

Film-coated tablet Oral administration

Also known as: HMR1726, Aubagio

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

Placebo DRUG

Film-coated tablet Oral administration

Placebo/Teriflunomide 7 mg or Teriflunomide 14 mg

Eligibility Criteria

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

You may qualify if:

• First acute or subacute, well-defined neurological event consistent with demyelination (that is, optic neuritis confirmed by an ophthalmologist, spinal cord syndrome, brainstem/cerebellar syndromes)
• Onset of MS symptoms occurring within 90 days of randomization
• A screening MRI scan with 2 or more T2 lesions at least 3 millimeter (mm) in diameter that are characteristic of MS

You may not qualify if:

• Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease
• Significantly impaired bone marrow function
• Pregnancy or nursing
• Alcohol or drug abuse
• Use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate before enrollment
• 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 (131)

Investigational Site Number 8965

Cullman, Alabama, 35058, United States

Location

Investigational Site Number 8954

Phoenix, Arizona, 85013-4496, United States

Location

Investigational Site Number 8946

Phoenix, Arizona, 85060, United States

Location

Investigational Site Number 8962

Fort Collins, Colorado, 80528, United States

Location

Investigational Site Number 8920

Maitland, Florida, 32761, United States

Location

Investigational Site Number 8953

St. Petersburg, Florida, 33701, United States

Location

Investigational Site Number 8914

Fort Wayne, Indiana, 63104, United States

Location

Investigational Site Number 8940

Indianapolis, Indiana, 46256, United States

Location

Investigational Site Number 8922

Shreveport, Louisiana, 71103, United States

Location

Investigational Site Number 8955

Grand Rapids, Michigan, 49503, United States

Location

Investigational Site Number 8949

Traverse City, Michigan, 49684, United States

Location

Investigational Site Number 8937

St Louis, Missouri, 63104, United States

Location

Investigational Site Number 8951

Albuquerque, New Mexico, 87131, United States

Location

Investigational Site Number 8925

New York, New York, 10029-6574, United States

Location

Investigational Site Number 8941

Charlotte, North Carolina, 28204, United States

Location

Investigational Site Number 8924

Dayton, Ohio, 45409, United States

Location

Investigational Site Number 8905

Round Rock, Tennessee, 78681, United States

Location

Investigational Site Number 8930

Burlington, Vermont, 05401, United States

Location

Investigational Site Number 8963

Seattle, Washington, 98122, United States

Location

Investigational Site Number 1405

Geelong, 3220, Australia

Location

Investigational Site Number 1404

Heidelberg, 3081, Australia

Location

Investigational Site Number 1407

Hobart, 7001, Australia

Location

Investigational Site Number 1401

Parkville, 3050, Australia

Location

Investigational Site Number 4004

Innsbruck, 6020, Austria

Location

Investigational Site Number 4005

Linz, 4020, Austria

Location

Investigational Site Number 4001

Vienna, 1010, Austria

Location

Investigational Site Number 5312

Pleven, 5800, Bulgaria

Location

Investigational Site Number 5307

Sofia, 1000, Bulgaria

Location

Investigational Site Number 5304

Sofia, 1407, Bulgaria

Location

Investigational Site Number 5309

Sofia, 1431, Bulgaria

Location

Investigational Site Number 5303

Sofia, 1527, Bulgaria

Location

Investigational Site Number 5306

Sofia, 1606, Bulgaria

Location

Investigational Site Number 5402

Greenfield Park, J4V 2J2, Canada

Location

Investigational Site Number 5403

London, N6A 5A5, Canada

Location

Investigational Site Number 5409

Montreal, H1T 2M4, Canada

Location

Investigational Site Number 5401

Ottawa, K1H 8L6, Canada

Location

Investigational Site Number 5406

Québec, G1J 1Z4, Canada

Location

Investigational Site Number 5408

Sherbrooke, J1H 5N4, Canada

Location

Investigational Site Number 5410

Toronto, M4N 3M5, Canada

Location

Investigational Site Number 5404

Toronto, M5B 1W8, Canada

Location

Investigational Site Number 5602

Santiago, 760-0746, Chile

Location

Investigational Site Number 5601

Santiago, Chile

Location

Investigational Site Number 5606

Santiago, Chile

Location

Investigational Site Number 5605

Viña del Mar, 2520997, Chile

Location

Investigational Site Number 5801

Brno, 65691, Czechia

Location

Investigational Site Number 5803

Hradec Králové, 50005, Czechia

Location

Investigational Site Number 5804

Olomouc, 77520, Czechia

Location

Investigational Site Number 5805

Ostrava - Poruba, 70852, Czechia

Location

Investigational Site Number 6002

Aarhus C, 8000, Denmark

Location

Investigational Site Number 6004

Esbjerg, 6700, Denmark

Location

Investigational Site Number 6201

Tallinn, 10617, Estonia

Location

Investigational Site Number 6203

Tartu, 50406, Estonia

Location

Investigational Site Number 6405

Helsinki, 00100, Finland

Location

Investigational Site Number 6403

Kuopio, 70210, Finland

Location

Investigational Site Number 6401

Turku, 20100, Finland

Location

Investigational Site Number 6611

Besançon, 25030, France

Location

Investigational Site Number 6601

Clermont-Ferrand, 63003, France

Location

Investigational Site Number 6609

Lille, 59037, France

Location

Investigational Site Number 6604

Montpellier, 34295, France

Location

Investigational Site Number 6612

Nancy, 54036, France

Location

Investigational Site Number 6605

Nantes, 44093, France

Location

Investigational Site Number 6602

Nice, 06002, France

Location

Investigational Site Number 6614

Nîmes, 30029, France

Location

Investigational Site Number 6607

Strasbourg, 67091, France

Location

Investigational Site Number 6801

Bayreuth, 95445, Germany

Location

Investigational Site Number 6810

Berlin, 10713, Germany

Location

Investigational Site Number 6805

Berlin, 10785, Germany

Location

Investigational Site Number 6807

Erbach im Odenwald, 64711, Germany

Location

Investigational Site Number 6803

Essen, 45122, Germany

Location

Investigational Site Number 6809

Hanover, 30625, Germany

Location

Investigational Site Number 6804

Ludwigshafen, 67063, Germany

Location

Investigational Site Number 6815

Minden, 32429, Germany

Location

Investigational Site Number 6802

Münster, 48149, Germany

Location

Investigational Site Number 6806

Wiesbaden, 65191, Germany

Location

Investigational Site Number 7101

Budapest, 1076, Hungary

Location

Investigational Site Number 7103

Budapest, 1145, Hungary

Location

Investigational Site Number 7108

Esztergom, 2500, Hungary

Location

Investigational Site Number 7105

Veszprém, 8200, Hungary

Location

Investigational Site Number 7402

Klaipėda, LT-92288, Lithuania

Location

Investigational Site Number 7403

Šiauliai, LT-76231, Lithuania

Location

Investigational Site Number 7401

Vilnius, LT-08661, Lithuania

Location

Investigational Site Number 7501

Chihuahua City, 31203, Mexico

Location

Investigational Site Number 7502

Guadalajara, 45110, Mexico

Location

Investigational Site Number 7709

Gdansk, 80-803, Poland

Location

Investigational Site Number 7710

Lodz, 93-513, Poland

Location

Investigational Site Number 7701

Warsaw, 02-097, Poland

Location

Investigational Site Number 7703

Warsaw, 02-957, Poland

Location

Investigational Site Number 7707

Warsaw, 04-141, Poland

Location

Investigational Site Number 7803

Bucharest, 020125, Romania

Location

Investigational Site Number 7806

Bucharest, 050098, Romania

Location

Investigational Site Number 7805

Cluj-Napoca, 400012, Romania

Location

Investigational Site Number 7807

Cluj-Napoca, 400012, Romania

Location

Investigational Site Number 7808

Timișoara, 300736, Romania

Location

Investigational Site Number 7907

Kazan', 420021, Russia

Location

Investigational Site Number 7909

Nizhny Novgorod, 603000, Russia

Location

Investigational Site Number 7906

Nizhny Novgorod, 603076, Russia

Location

Investigational Site Number 7904

Nizhny Novgorod, 603126, Russia

Location

Investigational Site Number 7912

Novosibirsk, 630007, Russia

Location

Investigational Site Number 7910

Rostov-on-Don, 344085, Russia

Location

Investigational Site Number 7911

Saint Petersburg, 194044, Russia

Location

Investigational Site Number 7905

Smolensk, 214019, Russia

Location

Investigational Site Number 8304

Edirne, Turkey (Türkiye)

Location

Investigational Site Number 8309

Istanbul, 34390, Turkey (Türkiye)

Location

Investigational Site Number 8315

Istanbul, 34400, Turkey (Türkiye)

Location

Investigational Site Number 8308

Istanbul, Turkey (Türkiye)

Location

Investigational Site Number 8310

Istanbul, Turkey (Türkiye)

Location

Investigational Site Number 8312

Istanbul, Turkey (Türkiye)

Location

Investigational Site Number 8305

Izmir, 35100, Turkey (Türkiye)

Location

Investigational Site Number 8301

Izmir, 35340, Turkey (Türkiye)

Location

Investigational Site Number 8303

Izmir, 35380, Turkey (Türkiye)

Location

Investigational Site Number 8302

İzmit, 41380, Turkey (Türkiye)

Location

Investigational Site Number 8314

Trabzon, 61080, Turkey (Türkiye)

Location

Investigational Site Number 8507

Chernihiv, 14029, Ukraine

Location

Investigational Site Number 8501

Dnipropetrovsk, 49027, Ukraine

Location

Investigational Site Number 8511

Donets'K, 83099, Ukraine

Location

Investigational Site Number 8506

Kharkiv, 61018, Ukraine

Location

Investigational Site Number 8504

Kharkiv, 61178, Ukraine

Location

Investigational Site Number 8508

Kiev, 03110, Ukraine

Location

Investigational Site Number 8512

Lutsk, 43005, Ukraine

Location

Investigational Site Number 8505

Lviv, 79010, Ukraine

Location

Investigational Site Number 8510

Poltava, 36011, Ukraine

Location

Investigational Site Number 8503

Vinnytsia, 21005, Ukraine

Location

Investigational Site Number 8502

Zaporizhzhya, 69000, Ukraine

Location

Investigational Site Number 8709

Liverpool, L9 7LJ, United Kingdom

Location

Investigational Site Number 8701

London, E1 1BB, United Kingdom

Location

Investigational Site Number 8704

London, SW17 0QT, United Kingdom

Location

Investigational Site Number 8706

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

Investigational Site Number 8705

Nottingham, NG7 2UH, United Kingdom

Location

Investigational Site Number 8708

Plymouth, PL6 5BX, United Kingdom

Location

Investigational Site Number 8707

Salford, M6 8HD, United Kingdom

Location

Investigational Site Number 8702

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• Miller AE, Wolinsky JS, Kappos L, Comi G, Freedman MS, Olsson TP, Bauer D, Benamor M, Truffinet P, O'Connor PW; TOPIC Study Group. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014 Oct;13(10):977-86. doi: 10.1016/S1474-4422(14)70191-7. Epub 2014 Sep 2.

  PMID: 25192851 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Recurrence

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: February 14, 2008
• First Posted: February 25, 2008
• Study Start: February 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: February 1, 2016
• Last Updated: March 13, 2017
• Results First Posted: December 19, 2014

Record last verified: 2017-01

Locations

AU (3); FR (9); DE (10); FI (3); CA (8); GB (8); US (19); ES (2); HU (4); LI (3); CZ (4); UA (11); ME (2); RU (8); PL (5); DK (2); RO (5); BU (6); CL (4); TU (11)