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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00340834




Registration number
NCT00340834
Ethics application status
Date submitted
19/06/2006
Date registered
21/06/2006
Date last updated
21/09/2017

Titles & IDs
Public title
Efficacy and Safety of Fingolimod in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase
Scientific title
A 12-month Double-blind, Randomized, Multicenter, Active-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5 mg and 1.25 mg Fingolimod (FTY720) Administered Orally Once Daily Versus Interferon ß-1a (Avonex) Administered im Once Weekly in Patients With Relapsing-remitting Multiple Sclerosis With Optional Extension Phase
Secondary ID [1] 0 0
CFTY720D2302E1
Secondary ID [2] 0 0
CFTY720D2302
Universal Trial Number (UTN)
Trial acronym
TRANSFORMS
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 - Fingolimod 1.25 mg
Treatment: Drugs - Fingolimod 0.5 mg
Treatment: Drugs - Interferon ß-1a 30 µg

Experimental: Fingolimod 1.25 mg -

Experimental: Fingolimod 0.5 mg -

Active comparator: Interferon ß-1a 30 µg -


Treatment: Drugs: Fingolimod 1.25 mg
Core: Patients self-administered fingolimod 1.25 mg capsules orally once daily. In addition, they self-administered an interferon ß-1a placebo intramuscular (im) injection once weekly.

Extension: Patients self-administered fingolimod 1.25 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.

Treatment: Drugs: Fingolimod 0.5 mg
Core: Patients self-administered fingolimod 0.5 mg capsules orally once daily. In addition, they self-administered an interferon ß-1a placebo intramuscular (im) injection once weekly.

Extension: Patients self-administered fingolimod 0.5 mg capsules orally once daily.

Treatment: Drugs: Interferon ß-1a 30 µg
Core: Patients self-administered interferon ß-1a 30 µg in an intramuscular (im) injection once weekly. In addition, they self-administered a fingolimod placebo capsule orally once daily.

Extension: Patients self-administered either fingolimod 1.25 mg or 0.5 mg capsules orally once daily until switched to 0.5 mg capsules upon study protocol amendment.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Estimated Annualized Aggregate Relapse Rate (ARR) in the Core Phase of the Study
Timepoint [1] 0 0
Baseline to Month 12
Secondary outcome [1] 0 0
Number of New or Newly Enlarged T2 Lesions in Comparison With Baseline in the Core Phase of the Study
Timepoint [1] 0 0
Baseline to Month 12
Secondary outcome [2] 0 0
Percentage of Participants Free of 3-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Core Phase of the Study
Timepoint [2] 0 0
Baseline to Month 12
Secondary outcome [3] 0 0
Estimated Annualized Aggregate Relapse Rate (ARR) in the Core and Extension Phases of the Study
Timepoint [3] 0 0
Month 0 to end of study (up to approximately 4.5 years)
Secondary outcome [4] 0 0
Number of New or Newly Enlarged T2 Lesions in the Extension Phase of the Study
Timepoint [4] 0 0
Month 12 to end of study (up to approximately 3.5 years)
Secondary outcome [5] 0 0
Percentage of Participants Free of 3-month and 6-month Disability Progression Assessed With the Expanded Disability Status Scale (EDSS) at the End of the Extension Phase of the Study
Timepoint [5] 0 0
Baseline to end of study (up to approximately 4.5 years)

Eligibility
Key inclusion criteria
* Male and female patients between ages 18-55 with a diagnosis of multiple sclerosis (MS)
* Patients with a relapsing-remitting disease course
* Patients with Expanded Disability Status Scale (EDSS) score of 0-5.5
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients with other chronic disease of the immune system, malignancies, acute pulmonary disease, cardiac failure, etc
* Pregnant or nursing women
* Patients who cannot tolerate treatment with an interferon

Other protocol-defined inclusion/exclusion criteria applied to the study.

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 administering the treatment/s
The people assessing the outcomes
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
1/05/2006
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2011
Sample size
Target
Accrual to date
Final
1292
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Strategic Health Evaluators - Chatswood
Recruitment hospital [2] 0 0
Royal Prince Alfred Hospital - Department of Medicine, Level, Missenden R, Camperdown
Recruitment hospital [3] 0 0
Liverpool Hospital, Neurology Department, Health Services Building, 4th Floor, Goulburn and Campbell Street - Liverpool
Recruitment hospital [4] 0 0
Gosford Private Hospital - North Gosford
Recruitment hospital [5] 0 0
St George Private Hospital - Suite 7E, Level 5, South Street, Kogarah
Recruitment hospital [6] 0 0
Box Hill Hopsital, Level 3, 16 Arnold Street - Box Hill
Recruitment hospital [7] 0 0
Royal Melbourne Hospital - Suite 30, Grattan St., Parkbville
Recruitment postcode(s) [1] 0 0
2067 - Chatswood
Recruitment postcode(s) [2] 0 0
2050 - Department of Medicine, Level, Missenden R, Camperdown
Recruitment postcode(s) [3] 0 0
2170 - Liverpool
Recruitment postcode(s) [4] 0 0
2250 - North Gosford
Recruitment postcode(s) [5] 0 0
2217 - Suite 7E, Level 5, South Street, Kogarah
Recruitment postcode(s) [6] 0 0
3128 - Box Hill
Recruitment postcode(s) [7] 0 0
3050 - Suite 30, Grattan St., Parkbville
Recruitment outside Australia
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Alabama
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Santa Fe
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Argentina
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Cordoba
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Argentina
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General Urquiza 609, Buenos Aires
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Argentina
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Montaneses 2325, Buenos Aires
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Austria
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Sankt Poelten
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Austria
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Abteilung fuer Neurologie, Linz
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Austria
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Anichstrasse 35, Innsbruck
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Austria
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Ignaz Harrerstr. 79 , Salzburg
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Austria
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Vienna
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Belgium
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Avenue Hippocrate 10, Bruxelles
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Belgium
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Laarbeeklaan 101, Brussels
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Belgium
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Melsbroek
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Sint-Truiden
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BA
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u. 8-20m, Budapest
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Uzsoki u. 29., Budapest
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Viale Giovan Battista Morgagni, 85, Firenze
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Porto
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Avda. Carlos Haya, s/n, Málaga
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Avenida Dr. Fedriani, 3, Sevilla
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Barcelona
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Bilbao
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C/ Dr. Martin Lagos, s/n, Madrid
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EUI-planta 2, Pg. Vall d'Hebron 119-29, Barcelona
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Spain
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San Martin de Porres, 4, Madrid
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Spain
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Valencia
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Switzerland
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Neurologische Klinik, Frauenklinikstrasse 26, Zuerich
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Switzerland
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Petersgraben 4, Basel
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United Kingdom
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Investigational Site
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London
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Lower Lane, Fazakerly, Liverpool
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United Kingdom
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Norwick

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

Ethics approval
Ethics application status

Summary
Brief summary
This study assessed the safety, tolerability, and efficacy of 2 doses of oral fingolimod versus interferon ß-1a to reduce the frequency of relapses in patients with relapsing-remitting multiple sclerosis.
Trial website
https://clinicaltrials.gov/study/NCT00340834
Trial related presentations / publications
Cohen JA, Khatri B, Barkhof F, Comi G, Hartung HP, Montalban X, Pelletier J, Stites T, Ritter S, von Rosenstiel P, Tomic D, Kappos L; TRANSFORMS (TRial Assessing injectable interferoN vS. FTY720 Oral in RRMS) Study Group. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016 May;87(5):468-75. doi: 10.1136/jnnp-2015-310597. Epub 2015 Jun 25.
Khatri BO, Pelletier J, Kappos L, Hartung HP, Comi G, Barkhof F, von Rosenstiel P, Meng X, Grinspan A, Hashmonay R, Cohen JA; TRANSFORMS Study Group. Effect of prior treatment status and reasons for discontinuation on the efficacy and safety of fingolimod vs. interferon beta-1a intramuscular: Subgroup analyses of the Trial Assessing Injectable Interferon vs. Fingolimod Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS). Mult Scler Relat Disord. 2014 May;3(3):355-63. doi: 10.1016/j.msard.2013.11.006. Epub 2013 Dec 12.
Chinea Martinez AR, Correale J, Coyle PK, Meng X, Tenenbaum N. Efficacy and safety of fingolimod in Hispanic patients with multiple sclerosis: pooled clinical trial analyses. Adv Ther. 2014 Oct;31(10):1072-81. doi: 10.1007/s12325-014-0154-4. Epub 2014 Sep 23.
Zarbin MA, Jampol LM, Jager RD, Reder AT, Francis G, Collins W, Tang D, Zhang X. Ophthalmic evaluations in clinical studies of fingolimod (FTY720) in multiple sclerosis. Ophthalmology. 2013 Jul;120(7):1432-9. doi: 10.1016/j.ophtha.2012.12.040. Epub 2013 Mar 24.
Khatri B, Barkhof F, Comi G, Hartung HP, Kappos L, Montalban X, Pelletier J, Stites T, Wu S, Holdbrook F, Zhang-Auberson L, Francis G, Cohen JA; TRANSFORMS Study Group. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011 Jun;10(6):520-9. doi: 10.1016/S1474-4422(11)70099-0. Epub 2011 May 13.
Twiss J, Doward LC, McKenna SP, Eckert B. Interpreting scores on multiple sclerosis-specific patient reported outcome measures (the PRIMUS and U-FIS). Health Qual Life Outcomes. 2010 Oct 11;8:117. doi: 10.1186/1477-7525-8-117.
Cohen JA, Barkhof F, Comi G, Hartung HP, Khatri BO, Montalban X, Pelletier J, Capra R, Gallo P, Izquierdo G, Tiel-Wilck K, de Vera A, Jin J, Stites T, Wu S, Aradhye S, Kappos L; TRANSFORMS Study Group. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med. 2010 Feb 4;362(5):402-15. doi: 10.1056/NEJMoa0907839. Epub 2010 Jan 20.
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmacuticals
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/NCT00340834