Relapsing Remitting Multiple Sclerosis (RRMS)Phase 3TOFIINGONCT01499667

Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod

A Phase 3 study testing Fingolimod in people with Relapsing Remitting Multiple Sclerosis (RRMS), run by Novartis Pharmaceuticals at 44 sites in 11 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Relapsing Remitting Multiple Sclerosis (RRMS)
What is being tested?: Fingolimod
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 142 participants
Where: 44 sitesin 11 countries
Study dates: Sep 2011to Nov 2012
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients must:
Have relapsing remitting multiple sclerosis
Have been on treatment with natalizumab for at least 6 months prior to screening and discontinuation is an option.

Who cannot join

Patients with:
History of chronic immune disease
Crohn's disease
Certain cancers
Uncontrolled diabetes
Certain eye disorders

Show all 14Show fewer

Negative for varicella-zoster virus IgG antibodies
Certain hepatic conditions
Low white blood cell count
On certain immunosuppressive medications or heart medications
Resting heart rate less than 45 bpm.
Certain heart conditions or certain lung conditions
Inability to undergo MRI scans
Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

44 sites in 11 countries.

Country

City, postcode or hospital

44 sites in 11 countries

Germany20 sites

Novartis Investigative Site
Bad Mergentheim, 97980
Novartis Investigative Site
Berlin, 10713
Novartis Investigative Site
Berlin, 12163
Novartis Investigative Site
Bielefeld, 33647
Novartis Investigative Site
Bochum, 44791
Novartis Investigative Site
Celle, Germany, 29223
Novartis Investigative Site
Erbach im Odenwald, 64711
Novartis Investigative Site
Erfurt, 99089
Novartis Investigative Site
Hamburg, 22083
Novartis Investigative Site
Itzehoe, 25524
Novartis Investigative Site
Kandel, 76870
Novartis Investigative Site
Krefeld, 47805
Novartis Investigative Site
Leipzig, 04275
Novartis Investigative Site
Münster, 48149
Novartis Investigative Site
Neuburg am Inn, 86633
Novartis Investigative Site
Neuruppin, 16816
Novartis Investigative Site
Ostfildern, Baden-Wurttemberg, 73760
Novartis Investigative Site
Rüdersdorf, 15562
Novartis Investigative Site
Siegen, 57076
Novartis Investigative Site
Ulm, 89073

Other trials in Germany

Greece5 sites

Novartis Investigative Site
Athens, GR, 115 25
Novartis Investigative Site
Athens, GR 151 25
Novartis Investigative Site
Athens, GR-106 76
Novartis Investigative Site
Ioannina, GR, 455 00
Novartis Investigative Site
Thessaloniki, GR, 570 10

Other trials in Greece

Spain5 sites

Novartis Investigative Site
Barcelona, Barcelona, 08025
Novartis Investigative Site
Barcelona, Catalonia, 08035
Novartis Investigative Site
Madrid, Madrid, 28046
Novartis Investigative Site
Málaga, Andalusia, 29010
Novartis Investigative Site
Seville, Andalusia, 41009

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Czechia3 sites

Novartis Investigative Site
Prague, 128 08
Novartis Investigative Site
Prague, 150 00
Novartis Investigative Site
Teplice, 415 29

Other trials in Czechia

Australia2 sites

Novartis Investigative Site
Box Hill, Victoria, 3128
Novartis Investigative Site
Heidelberg, Victoria, 3084

Other trials in Australia

Hungary2 sites

Novartis Investigative Site
Budapest, 1074
Novartis Investigative Site
Budapest, 1085

Other trials in Hungary

Israel2 sites

Novartis Investigative Site
Ashkelon, 78278
Novartis Investigative Site
Jerusalem, 91120

Other trials in Israel

Italy2 sites

Novartis Investigative Site
Cefalù, PA, 90015
Novartis Investigative Site
Milan, MI, 20132

Other trials in Italy

Austria1 site

Novartis Investigative Site
Vienna, 1010

Other trials in Austria

Finland1 site

Novartis Investigative Site
Helsinki, 00100

Other trials in Finland

Switzerland1 site

Novartis Investigative Site
Basel, 4031

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About this study

Official title: A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720)

This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod.

Read the detailed description

Patient were screened, signed an informed consent at visit 1, at the 2nd visit, all patient received a baseline infusion of Natalizumub and subsequently randomized to one of 3 treatment arms. At the randomization visit, the Washout Phase started, and eligible patients were randomized 1:1:1 to one of three treatment groups:

8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod,
12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod, or
16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod.

Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)
Being tested: Fingolimod, Placebo
Keywords: Relapsing remitting multiple sclerosis, multiple sclerosis (MS), safety, tolerability, health outcomes, fingolimod, disease control, MRI
Medical subject headings: Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

FingolimodDrug
Fingolimod 0.5 mg capsules for oral administration once daily
PlaceboDrug
Matching placebo in capsules for oral administration once daily.

Study groups in NCT01499667
Study group	Role	What they receive
8-week washout + Fingolimod (FTY720)	Experimental	8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day Receives: Drug: Fingolimod
12-week washout + Fingolimod (FTY720)	Experimental	12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day Receives: Drug: Fingolimod; Drug: Placebo
16-week washout + Fingolimod (FTY720)	Experimental	16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day Receives: Drug: Fingolimod; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group.
Measured: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment

Secondary outcomes (7)

Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated from baseline to beginning of treatment.
Measured: 8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
Lesions were measured by MRIs and the number of active (new or newly enlarging) T2 lesions was calculated for first 8 weeks of fingolimod treatment.
Measured: Number of active T2 lesions during 8 wks of fingolimod treatment
Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
Lesions will be measured by MRIs and the number of active (new or newly enlarging) T2 lesions will be calculated for 24 weeks from baseline.
Measured: Baseline up to 24 weeks
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
Kurtzke's Expanded Disability Status Scale (EDSS) measures the changes in neurologic impairment, either chronic (progression over time), or acute (MS relapses). The EDSS steps range from 0 (normal) to 10 (death due to MS). Relapse severity is assessed based on severity of neurologic impairment as evaluated using the EDSS.
Measured: Baseline to week 16 and week 32
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
Gadolinium-enhancing lesions will be measured on post-contrast T1-weighted brain MRI scans
Measured: 8 weeks and 24 weeks
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
Adverse events were summarized by the number of patients having any adverse event overall.
Measured: Baseline to maximum of 16 weeks
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
Adverse events were summarized by the number of patients having any adverse event overall.
Measured: Baseline to maximum of 16 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011Nov 2012

First posted26 Dec 2011 (estimated)
Study startSep 2011
Primary completionNov 2012
Study completionNov 2012

Why it stopped: Based on recent publications, determination of natalizumub washout period was no longer relevant.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Relapsing Remitting Multiple Sclerosis (RRMS)Studies of the same condition, open and under way.
More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 142 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01499667
Sponsor's protocol ID: CFTY720D2324
Other IDs: 2011-001442-15
Acronym: TOFIINGO
Status last verified: Aug 2014
First submitted: 18 Aug 2011
Last updated: 8 Aug 2014
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Derfuss T, Kovarik JM, Kappos L, Savelieva M, Chhabra R, Thakur A, Zhang Y, Wiendl H, Tomic D. alpha4-integrin receptor desaturation and disease activity return after natalizumab cessation. Neurol Neuroimmunol Neuroinflamm. 2017 Aug 25;4(5):e388. doi: 10.1212/NXI.0000000000000388. eCollection 2017 Sep.
PubMed 28856176

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 32-week, Patient- and Rater-blinded, Randomized, Multi-center, Parallel-group Study to Evaluate Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis Transferred From Previous Treatment With Natalizumab to Fingolimod (FTY720)
ClinicalTrials.gov ID: NCT01499667
Acronym / sponsor ID: TOFIINGO / CFTY720D2324
Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)
Keywords: Relapsing remitting multiple sclerosis, multiple sclerosis (MS), safety, tolerability, health outcomes, fingolimod, disease control, MRI
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Based on recent publications, determination of natalizumub washout period was no longer relevant.
Enrolment: 142 participants (actual)
Lead sponsor: Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
Study start: Sep 2011
Primary completion: Nov 2012 (actual)
Study completion: Nov 2012 (actual)
First posted: 26 Dec 2011 (estimated)
Results: Posted 4 Apr 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study evaluated disease control during different lengths of treatment transition from natalizumab to fingolimod.

Detailed description

8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod,
12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod, or
16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
8-week washout + Fingolimod (FTY720)	Experimental	Drug: Fingolimod8-week washout (8 weeks no treatment) followed by 24 weeks of treatment with fingolimod 0.5mg once a day
12-week washout + Fingolimod (FTY720)	Experimental	Drug: Fingolimod, Drug: Placebo12-week washout (8 weeks no treatment and 4 weeks placebo) followed by 20 weeks of treatment with fingolimod 0.5mg once a day
16-week washout + Fingolimod (FTY720)	Experimental	Drug: Fingolimod, Drug: Placebo16-week washout (8 weeks no treatment and 8 weeks placebo) followed by 16 weeks of treatment with fingolimod 0.5mg once a day

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

Have relapsing remitting multiple sclerosis
Have been on treatment with natalizumab for at least 6 months prior to screening and discontinuation is an option.

Key exclusion criteria (14 listed)

History of chronic immune disease
Crohn's disease
Certain cancers
Uncontrolled diabetes
Certain eye disorders

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
FingolimodFingolimod 0.5 mg capsules for oral administration once daily	Drug	12-week washout + Fingolimod (FTY720), 16-week washout + Fingolimod (FTY720), 8-week washout + Fingolimod (FTY720)
PlaceboMatching placebo in capsules for oral administration once daily.	Drug	12-week washout + Fingolimod (FTY720), 16-week washout + Fingolimod (FTY720)

Primary outcome

Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
Time frame: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment
Active lesions were measured on brain MRI scans, performed at week 8, compared to the prior scan. The primary variable was analyzed by fitting a negative binomial regression model adjusted for washout group.

7 secondary outcomes

Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
Time frame: 8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
Time frame: Number of active T2 lesions during 8 wks of fingolimod treatment
Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
Time frame: Baseline up to 24 weeks
Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
Time frame: Baseline to week 16 and week 32
Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
Time frame: 8 weeks and 24 weeks
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
Time frame: Baseline to maximum of 16 weeks
Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
Time frame: Baseline to maximum of 16 weeks

Results and safety

Results posted to the registry on 4 Apr 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
8-week Washout + Fingolimod (FTY720)	50	41
12-week Washout + Fingolimod (FTY720)	42	31
16-week Washout + Fingolimod (FTY720)	50	40

Primary outcome: Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment

Time frame: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment. Mean (Standard Deviation). Unit: Count of Active T2 Lesions

Measure	8-week Washout + Fingolimod (FTY720) n = 41	12-week Washout + Fingolimod (FTY720) n = 29	16-week Washout + Fingolimod (FTY720) n = 39
Value	2.1 (7.24)	1.7 (3.78)	8.2 (16.81)

Population analysed: The modified Full Analysis Set (mFAS) included all patients in the Full Analysis Set who completed 8 weeks of fingolimod treatment and provided an MRI scan at this time point. The analysis of primary variable was performed on the mFAS.

7 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
8-week Washout + Fingolimod (FTY720)	2 of 50 (4%)	17 of 50 (34%)	Not reported
12-week Washout + Fingolimod (FTY720)	5 of 42 (11.9%)	7 of 42 (16.7%)	Not reported
16-week Washout + Fingolimod (FTY720)	4 of 50 (8%)	14 of 50 (28%)	Not reported

Limitations and caveats (from the sponsor): Study was terminated due to new data on nataluzimab washout prior to treatment with other disease modifying treatments. The power to detect statistically significant differences between the washout groups based on the (-)binomial is estimated 30-40%.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 28856176Derfuss T, Kovarik JM, Kappos L, Savelieva M, Chhabra R, Thakur A, Zhang Y, Wiendl H, Tomic D. alpha4-integrin receptor desaturation and disease activity return after natalizumab cessation. Neurol Neuroimmunol Neuroinflamm. 2017 Aug 25;4(5):e388. doi: 10.1212/NXI.0000000000000388. eCollection 2017 Sep.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Novartis Pharmaceuticals study director

Novartis Pharmaceuticals

44 sites in 11 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Fingolimod in people with Relapsing Remitting Multiple Sclerosis (RRMS), run by Novartis Pharmaceuticals at 44 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 44 sites in Germany, Greece, Spain, Czechia, Australia and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Apr 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment (time frame: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01499667, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2014; AzTrials last refreshed its copy on 6 Nov 2026.