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

NCT01499667 | Terminated Phase 3 Results

• 2 other identifiers: CFTY720D23242011-001442-15
• Study Type: interventional
• Target: 142
• Locations: 10 countries
• Sites: 42

Brief Summary

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

Conditions

Relapsing Remitting Multiple Sclerosis (RRMS)

Keywords

Relapsing remitting multiple sclerosis; multiple sclerosis (MS); safety; tolerability; health outcomes; fingolimod; disease control; MRI

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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)

  Baseline up to 24 weeks

• Change From Baseline in Expanded Disability Status Scale (EDSS) by Washout Group

  Baseline to week 16 and week 32

• Cumulative Number of Gadolinium-enhancing T1 Lesions From the Last Natalizumab Infusion

  8 weeks and 24 weeks

Study Arms (3)

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

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

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

Drug: Fingolimod; Drug: Placebo

Interventions

Fingolimod DRUG

Fingolimod 0.5 mg capsules for oral administration once daily

12-week washout + Fingolimod (FTY720); 16-week washout + Fingolimod (FTY720); 8-week washout + Fingolimod (FTY720)

Placebo DRUG

Matching placebo in capsules for oral administration once daily.

12-week washout + Fingolimod (FTY720); 16-week washout + Fingolimod (FTY720)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (44)

Novartis Investigative Site

Box Hill, Victoria, 3128, Australia

Location

Novartis Investigative Site

Heidelberg, Victoria, 3084, Australia

Location

Novartis Investigative Site

Vienna, 1010, Austria

Location

Novartis Investigative Site

Prague, 128 08, Czechia

Location

Novartis Investigative Site

Prague, 150 00, Czechia

Location

Novartis Investigative Site

Teplice, 415 29, Czechia

Location

Novartis Investigative Site

Helsinki, 00100, Finland

Location

Novartis Investigative Site

Ostfildern, Baden-Wurttemberg, 73760, Germany

Location

Novartis Investigative Site

Celle, Germany, 29223, Germany

Location

Novartis Investigative Site

Bad Mergentheim, 97980, Germany

Location

Novartis Investigative Site

Berlin, 10713, Germany

Location

Novartis Investigative Site

Berlin, 12163, Germany

Location

Novartis Investigative Site

Bielefeld, 33647, Germany

Location

Novartis Investigative Site

Bochum, 44791, Germany

Location

Novartis Investigative Site

Erbach im Odenwald, 64711, Germany

Location

Novartis Investigative Site

Erfurt, 99089, Germany

Location

Novartis Investigative Site

Hamburg, 22083, Germany

Location

Novartis Investigative Site

Itzehoe, 25524, Germany

Location

Novartis Investigative Site

Kandel, 76870, Germany

Location

Novartis Investigative Site

Krefeld, 47805, Germany

Location

Novartis Investigative Site

Leipzig, 04275, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Neuburg am Inn, 86633, Germany

Location

Novartis Investigative Site

Neuruppin, 16816, Germany

Location

Novartis Investigative Site

Rüdersdorf, 15562, Germany

Location

Novartis Investigative Site

Siegen, 57076, Germany

Location

Novartis Investigative Site

Ulm, 89073, Germany

Location

Novartis Investigative Site

Athens, GR, 115 25, Greece

Location

Novartis Investigative Site

Ioannina, GR, 455 00, Greece

Location

Novartis Investigative Site

Thessaloniki, GR, 570 10, Greece

Location

Novartis Investigative Site

Athens, GR 151 25, Greece

Location

Novartis Investigative Site

Athens, GR-106 76, Greece

Location

Novartis Investigative Site

Budapest, 1074, Hungary

Location

Novartis Investigative Site

Budapest, 1085, Hungary

Location

Novartis Investigative Site

Ashkelon, 78278, Israel

Location

Novartis Investigative Site

Jerusalem, 91120, Israel

Location

Novartis Investigative Site

Milan, MI, 20132, Italy

Location

Novartis Investigative Site

Cefalù, PA, 90015, Italy

Location

Novartis Investigative Site

Málaga, Andalusia, 29010, Spain

Location

Novartis Investigative Site

Seville, Andalusia, 41009, Spain

Location

Novartis Investigative Site

Barcelona, Barcelona, 08025, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Madrid, Madrid, 28046, Spain

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 28856176 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Fingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sphingosine; Amino Alcohols; Alcohols; Organic Chemicals; Propylene Glycols; Glycols; Amines

Limitations and Caveats

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%.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharnaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  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, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2011
• First Posted: December 26, 2011
• Study Start: September 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: August 8, 2014
• Results First Posted: April 4, 2014

Record last verified: 2014-08

Locations

IT (2); CH (1); HU (2); FI (1); GR (5); CZ (3); IL (2); ES (5); AU (1); DE (20)