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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00751881




Registration number
NCT00751881
Ethics application status
Date submitted
7/05/2008
Date registered
12/09/2008
Date last updated
7/07/2016

Titles & IDs
Public title
An Efficacy Study of Teriflunomide in Participants With Relapsing Multiple Sclerosis
Scientific title
A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis
Secondary ID [1] 0 0
2007-004452-36
Secondary ID [2] 0 0
EFC10531
Universal Trial Number (UTN)
Trial acronym
TOWER
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - Teriflunomide

Experimental: Teriflunomide 7 mg / 14 mg - Core treatment period: Teriflunomide 7 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.

Experimental: Teriflunomide 14 mg / 14 mg - Core treatment period: Teriflunomide 14 mg once daily. Extension treatment period: Teriflunomide 14 mg once daily.

Placebo comparator: Placebo / Teriflunomide 14 mg - Core treatment period: Placebo (for teriflunomide) once daily. Extension treatment period: Teriflunomide 14 mg once daily.


Treatment: Drugs: Placebo
Film-coated tablet

Oral administration

Treatment: Drugs: Teriflunomide
Film-coated tablet

Oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Core Treatment Period: Annualized Relapse Rate (ARR): Poisson Regression Estimate
Timepoint [1] 0 0
Core treatment period between 48 - 152 weeks depending on time of enrollment
Secondary outcome [1] 0 0
Core Treatment Period: Time to Disability Progression
Timepoint [1] 0 0
Core treatment period between 48 - 152 weeks depending on time of enrollment
Secondary outcome [2] 0 0
Core Treatment Period: Time Without Relapse
Timepoint [2] 0 0
Core treatment period between 48 - 152 weeks depending on time of enrollment
Secondary outcome [3] 0 0
Core Treatment Period: Change From Baseline to Week 48 in EDSS Total Score
Timepoint [3] 0 0
Baseline (before randomization), Week 12, Week 24, Week 36 and Week 48
Secondary outcome [4] 0 0
Core Treatment Period: Change From Baseline to Week 48 in Fatigue Impact Scale (FIS) Total Score
Timepoint [4] 0 0
Baseline (before randomization), Week 12, Week 24 and Week 48
Secondary outcome [5] 0 0
Core Treatment Period: Change From Baseline to Last Visit in Fatigue Impact Scale (FIS) Total Score
Timepoint [5] 0 0
Baseline (before randomization) and up to Week 152
Secondary outcome [6] 0 0
Core Treatment Period: Change From Baseline to Week 48 in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores
Timepoint [6] 0 0
Baseline (before randomization), Week 12, Week 24 and Week 48
Secondary outcome [7] 0 0
Core Treatment Period: Change From Baseline to Last Visit in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores
Timepoint [7] 0 0
Baseline (before randomization) and up to Week 152
Secondary outcome [8] 0 0
Core Treatment Period: Overview of Adverse Events
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Extension Treatment Period: Overview of Treatment Emergent Adverse Events (TEAE)
Timepoint [9] 0 0
From first intake of study drug in extension treatment period up to 28 days after the last intake in the extension treatment period
Secondary outcome [10] 0 0
Extension Treatment Period: Time to Disability Progression
Timepoint [10] 0 0
Core treatment period (maximum: 173 weeks) and Extension treatment period (maximum: 174 weeks)
Secondary outcome [11] 0 0
Extension Treatment Period: ARR: Poisson Regression Estimate
Timepoint [11] 0 0
Extension treatment period (Maximum: 174 weeks)

Eligibility
Key inclusion criteria
* Relapsing multiple sclerosis,
* Two relapses in prior 2 years or one relapse in prior year.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/08/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/08/2015
Sample size
Target
Accrual to date
Final
1169
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Investigational Site Number 036005 - Bedford Park
Recruitment hospital [2] 0 0
Sanofi-Aventis Investigational Site Number 036006 - Chatswood
Recruitment hospital [3] 0 0
Sanofi-Aventis Investigational Site Number 036003 - Fitzroy
Recruitment hospital [4] 0 0
Sanofi-Aventis Investigational Site Number 036004 - Geelong
Recruitment hospital [5] 0 0
Sanofi-Aventis Investigational Site Number 036008 - Heidelberg
Recruitment hospital [6] 0 0
Sanofi-Aventis Investigational Site Number 036002 - New Lambton
Recruitment hospital [7] 0 0
Sanofi-Aventis Investigational Site Number 036001 - Sydney
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
2067 - Chatswood
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
2305 - New Lambton
Recruitment postcode(s) [7] 0 0
2050 - Sydney
Recruitment outside Australia
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Istanbul
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Ukraine
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Ivano-Frankovsk
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Poltava
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Edinburgh
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Haywards Heath
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Irvine
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Leeds
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Salford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.

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.
Trial website
https://clinicaltrials.gov/study/NCT00751881
Trial related presentations / 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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Sciences & Operations
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00751881