Clinical trial NCT01499667: Disease Control and Safety in Patients With Relapsing Remitting Multiple Sclerosis (RRMS) Switching From Natalizumab to Fingolimod
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing Remitting Multiple Sclerosis (RRMS)
Keywords: Relapsing remitting multiple sclerosis
multiple sclerosis (MS)
safety
tolerability
health outcomes
fingolimod
disease control
MRI
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2011-12-26
Enrollment: 142
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: Inclusion Criteria:

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.

Exclusion Criteria:

Patients with:

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

Primary outcomes:
measure: Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) Through 8 Weeks of Fingolimod Treatment
timeFrame: Number of active T2 lesions from last natalizumab dose through 8 weeks of fingolimod treatment
Secondary outcomes:
measure: Number of Active (New or Newly Enlarging) T2 Lesions From the Last Natalizumab Infusion (Baseline) up to the Initiation of Fingolimod Treatment
timeFrame: 8, 12 and 16 weeks (number of active T2 lesions during the washout period only)
measure: Number of Active (New or Newly Enlarging) T2 Lesions During the First 8 Weeks of Fingolimod Treatment
timeFrame: Number of active T2 lesions during 8 wks of fingolimod treatment
measure: Number of Active (New or Newly Enlarging) T2 Lesions During the 24 Weeks After the Last Natalizumab Infusion (Baseline)
timeFrame: Baseline up to 24 weeks
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group
timeFrame: Baseline to week 16 and week 32
measure: Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion
timeFrame: 8 weeks and 24 weeks
measure: Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Washout Period
timeFrame: Baseline to maximum of 16 weeks
measure: Number of Participants With Adverse Events (AE), Serious Adverse Events (SAE) and Death During Fingolimod Treatment
timeFrame: Baseline to maximum of 16 weeks
Other outcomes:
Locations:
city: Box Hill
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Heidelberg
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Prague 5
country: Czech Republic
facility: Novartis Investigative Site
city: Praha 2
country: Czech Republic
facility: Novartis Investigative Site
city: Teplice
country: Czech Republic
facility: Novartis Investigative Site
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Ostfildern
country: Germany
facility: Novartis Investigative Site
state: Baden-Wuerttemberg
city: Bad Mergentheim
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Bielefeld
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Celle
country: Germany
facility: Novartis Investigative Site
city: Erbach
country: Germany
facility: Novartis Investigative Site
city: Erfurt
country: Germany
facility: Novartis Investigative Site
city: Hamburg
country: Germany
facility: Novartis Investigative Site
city: Itzehoe
country: Germany
facility: Novartis Investigative Site
city: Kandel
country: Germany
facility: Novartis Investigative Site
city: Krefeld
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Münster
country: Germany
facility: Novartis Investigative Site
city: Neuburg
country: Germany
facility: Novartis Investigative Site
city: Neuruppin
country: Germany
facility: Novartis Investigative Site
city: Rüdersdorf
country: Germany
facility: Novartis Investigative Site
city: Siegen
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Ioannina
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Ashkelon
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Cefalù
country: Italy
facility: Novartis Investigative Site
state: PA
city: Málaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Barcelona
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.