This Was an Open-label, Single-arm Extension Study (CFTY720D2306E1) to a Double-blind, Randomized Multicenter, Placebo-controlled, Parallel-group Core Study (CFTY720D2306) in PPMS.

NCT00731692 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: CFTY720D23062007-002627-32
• Study Type: interventional
• Target: 970
• Locations: 18 countries
• Sites: 157

Brief Summary

The purpose of this study is to evaluate whether FTY720 is effective in delaying MS disability progression compared to placebo in patients with PPMS. This was an open-label, single-arm extension study to a double-blind, randomized multicenter, placebo-controlled, parallel-group core study. The core study completed and eligible patients enrolled into the extension study at the next scheduled or unscheduled core study visit. All patients, regardless of their treatment in the core study, received fingolimod 0.5 mg in the extension study. The extension study was terminated early after the results of the core study became available showing that the study did not meet its primary endpoint which was defined as confirmed disability progression in this population

Conditions

Primary Progressive Multiple Sclerosis

Keywords

FTY720, primary progressive multiple sclerosis,PPMS

Outcome Measures

Primary Outcomes (1)

• Kaplan-Meier Estimate of the Risk of 3-month Confirmed Disability Progression Based on Composite Endpoint

  3-month sustained increase from Baseline in EDSS (at least 1 point increase from Baseline for patients with a Baseline value of 5 or less or at least 0.5 point increase from Baseline for patients with a Baseline value of 5.5 or more) or 3-month sustained increase of at least 20% from BL in the time taken to complete the timed 25-foot walk test (25' TWT); or 3-month sustained increase of at least 20% from BL in the time taken to complete the 9-HPT. The 25' TWT is a quantitative measure of lower extremity function. The EDSS is a scale assessing neurologic impairment, including a series of scores in each of 8 functional systems: Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. The score ranges from 0 (normal) to 10 (death due to MS)). The 9-hole peg test (9-HPT) is a quantitative measure of upper extremity (arm and hand) function.

  up to 36 months after the last patient was randomized

Secondary Outcomes (14)

• Kaplan-Meier Estimate of the Risk of 3- Month Confirmed Disability Progression Based on Expanded Disability Status Scale (EDSS)

  up to 36 months after the last patient was randomized

• Percent Change From Baseline in Brain Volume at Month 36

  Baseline to month 36

• Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 9-HPT.

  up to 36 months after the last patient was randomized

• Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 25' TWT.

  up to 36 months after the last patient was randomized

• Number of New/Enlarging T2 Lesions Per Year Measured From Baseline to Month 36

  Baseline to 36 months

Study Arms (3)

FTY720D 0.5 mg

EXPERIMENTAL

Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment

Drug: FTY720

Placebo

PLACEBO COMPARATOR

Cohort 1 and 2: Patients randomized to placebo continued on placebo after re-randomization

Drug: Placebo

FTY720D 1.25 mg switch to 0.5 mg

EXPERIMENTAL

Cohort 1: fingolimod 1.25 group consists of patients who were initially randomized to fingolimod 1.25 mg and switched to fingolimod 0.5 mg after amendment on Nov 2009

Drug: FTY720

Interventions

FTY720 DRUG

Fingolimod capsules at doses of 1.25 mg (prior to implementation of Amendment 5) and 0.5 mg (after Amendment 5) were administered orally once daily

FTY720D 0.5 mg; FTY720D 1.25 mg switch to 0.5 mg

Placebo DRUG

Matching placebo capsules were administered orally once daily

Placebo

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• General
• sign written informed consent prior to participating in the study
• through 65 years of age inclusive
• females of childbearing potential must:
• have a negative pregnancy test at Baseline (prior to randomization) and
• use simultaneously two forms of effective contraception during the treatment and 3-months after discontinuation of study medication
• Primary Progressive Multiple sclerosis.
• diagnosis of primary progressive multiple sclerosis (according to the 2005 Revised McDonald criteria):
• time since first reported symptoms between 2 and 10 years
• evidence of clinical disability progression in the 2 years prior to Screening
• disability status at Screening
• EDSS score of 3.5-6.0 inclusive
• pyramidal functional system score of 2 or more
• 'TWT less than 30 seconds
• Patients initially randomized to fingolimod 1.25 mg or placebo as part of the first study cohort, were to have completed at least 3 years on study drug treatment at the time of extension study initiation.

You may not qualify if:

• PPMS specific:
• History of relapses/attacks
• Progressive neurological disorder other than PPMS
• Pure cerebellar syndrome or pure visual progressive syndrome or pure
• cognitive progressive syndrome
• Presence of spinal cord compression at screening MRI
• Relevant history of vitamin B12 deficit
• Evidence of syphilis or borreliosis at Screening
• Cardiovascular conditions:
• Myocardial infarction within the past 6 months or current unstable ischemic heart disease
• History of angina pectoris due to coronary spasm or history of Raynaud's phenomenon
• Severe cardiac failure or cardiac arrest
• History of symptomatic bradycardia
• Resting pulse \<55 bpm pre-dose
• History of sick sinus syndrome or sino-atrial heart block

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (157)

Novartis Investigative Site

Newport Beach, California, 92660, United States

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Novartis Investigative Site

Sacramento, California, 95817, United States

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Aurora, Colorado, 80045, United States

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Pompano Beach, Florida, 33060, United States

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Novartis Investigative Site

Tampa, Florida, 33609, United States

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Atlanta, Georgia, 30302, United States

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Chicago, Illinois, 60611, United States

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Chicago, Illinois, 60637, United States

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Kansas City, Kansas, 66160, United States

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Baltimore, Maryland, 21287, United States

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Boston, Massachusetts, 02135, United States

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Brookline, Massachusetts, 02445, United States

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Detroit, Michigan, 48201, United States

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St Louis, Missouri, 63110, United States

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Teaneck, New Jersey, 07666, United States

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Buffalo, New York, 14203, United States

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New York, New York, 10029, United States

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Rochester, New York, 14642, United States

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Stony Brook, New York, 11794, United States

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Charlotte, North Carolina, 28207, United States

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Durham, North Carolina, 27705, United States

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Cleveland, Ohio, 44195, United States

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Columbus, Ohio, 43221, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Knoxville, Tennessee, 37934, United States

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Nashville, Tennessee, 37212, United States

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Dallas, Texas, 75390-9034, United States

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Houston, Texas, 77030, United States

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San Antonio, Texas, 78229, United States

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Burlington, Vermont, 05401, United States

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Charlottesville, Virginia, 22904, United States

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Seattle, Washington, 98122, United States

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Madison, Wisconsin, 53792, United States

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Camperdown, New South Wales, 2050, Australia

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Liverpool, New South Wales, 2170, Australia

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Hobart, Tasmania, 7000, Australia

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Box Hill, Victoria, 3128, Australia

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Heidelberg, Victoria, 3084, Australia

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Parkville, Victoria, 3050, Australia

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Charleroi, 6000, Belgium

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Edegem, 2650, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Melsbroek, 1820, Belgium

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Sint-Truiden, 3800, Belgium

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Calgary, Alberta, T2N 2T9, Canada

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Edmonton, Alberta, T6R 2B7, Canada

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Burnaby, British Columbia, V5G 2X6, Canada

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Vancouver, British Columbia, V6T 2B5, Canada

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Halifax, Nova Scotia, B3H 4K4, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M4N 3M5, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Gatineau, Quebec, J9J 0A5, Canada

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Greenfield Park, Quebec, J4V 2J2, Canada

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Montreal, Quebec, H2L 4M1, Canada

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Montreal, Quebec, H3A 2B4, Canada

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Regina, Saskatchewan, S4T 1A5, Canada

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Brno, Czech Republic, 656 91, Czechia

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Rychnov nad Kněžnou, Czech Republic, 516 01, Czechia

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Olomouc, CZE, 775 20, Czechia

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Ostrava-Poruba, 708 00, Czechia

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Pilsen, 301 00, Czechia

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Prague, 128 08, Czechia

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Teplice, 415 29, Czechia

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Aarhus, 8000 C, Denmark

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Sønderborg, 6400, Denmark

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Helsinki, 00930, Finland

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Tampere, 33100, Finland

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Turku, 20520, Finland

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Bordeaux, F-33076, France

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Lille, 59037, France

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Marseille, 13385, France

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Montpellier, 34295, France

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Nantes, 44093, France

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Paris, 75651, France

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Rennes, 35043, France

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Strasbourg, 67091, France

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Berlin, 10713, Germany

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Berlin, 13347, Germany

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Bochum, 44791, Germany

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Dresden, 01307, Germany

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Düsseldorf, D-40225, Germany

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Freiburg im Breisgau, 79106, Germany

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Hanover, 30625, Germany

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Hennigsdorf, 16761, Germany

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Magdeburg, 39120, Germany

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München, 81377, Germany

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München, 81675, Germany

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Münster, 48149, Germany

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Teupitz, 15755, Germany

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Trier, 54292, Germany

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Würzburg, 97080, Germany

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Budapest, 1076, Hungary

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Budapest, 1145, Hungary

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Debrecen, 4032, Hungary

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Győr, 9024, Hungary

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Miskolc, 3526, Hungary

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Veszprém, H-8200, Hungary

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Bari, BA, 70124, Italy

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Montichiari, BS, 25018, Italy

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Chieti, CH, 66100, Italy

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Catania, CT, 95123, Italy

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Genova, GE, 16132, Italy

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Milan, MI, 20122, Italy

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Milan, MI, 20132, Italy

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Cefalù, PA, 90015, Italy

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Padua, PD, 35128, Italy

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Roma, RM, 00133, Italy

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Roma, RM, 00189, Italy

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Orbassano, TO, 10043, Italy

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Gallarate, VA, 21013, Italy

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Breda, CK, 4818, Netherlands

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Amsterdam, 1105 AZ, Netherlands

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Eindhoven, 5623 EJ, Netherlands

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Nieuwegein, 3435 CM, Netherlands

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Nijmegen, 6525 GC, Netherlands

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Sittard-Geleen, 6162 BG, Netherlands

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Lodz, 90-153, Poland

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Lublin, 20-954, Poland

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Warsaw, 02-097, Poland

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Warsaw, 02-957, Poland

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Seville, Andalusia, 41009, Spain

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Bilbao, Basque Country, 48013, Spain

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Badalona, Catalonia, 08916, Spain

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Barcelona, Catalonia, 08035, Spain

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Barcelona, Catalonia, 08036, Spain

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Girona, Catalonia, 17007, Spain

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L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Lleida, Catalonia, 25198, Spain

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Majadahonda, Madrid, 28222, Spain

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Valencia, Valencia, 46026, Spain

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Madrid, 28040, Spain

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Madrid, 28046, Spain

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Gothenburg, 413 45, Sweden

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Stockholm, 17176, Sweden

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Basel, 4031, Switzerland

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Bern, 3010, Switzerland

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Lausanne, 1011, Switzerland

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Lugano, 6900, Switzerland

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Zurich, 8091, Switzerland

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Ankara, 06100, Turkey (Türkiye)

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Atakum / Samsun, 55139, Turkey (Türkiye)

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Balcova / Izmir, 35340, Turkey (Türkiye)

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Istanbul, 34093, Turkey (Türkiye)

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Yenisehir / Izmir, Turkey (Türkiye)

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Salford, Manchester, M6 8HD, United Kingdom

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Sheffield, South Yorkshire, S10 2JF, United Kingdom

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Bristol, BS10 5NB, United Kingdom

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London, EC1A 7BE, United Kingdom

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London, NW1 2BU, United Kingdom

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London, SE5 9RS, United Kingdom

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London, W8 6RF, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Norwich, NR4 7UY, United Kingdom

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Related Publications (7)

• Calvi A, Mendelsohn Z, Hamed W, Chard D, Tur C, Stutters J, MacManus D, Kanber B, Wheeler-Kingshott CAMG, Barkhof F, Prados F. Treatment reduces the incidence of newly appearing multiple sclerosis lesions evolving into chronic active, slowly expanding lesions: A retrospective analysis. Eur J Neurol. 2024 Jan;31(1):e16092. doi: 10.1111/ene.16092. Epub 2023 Oct 12.

  PMID: 37823722 DERIVED

• Leppert D, Kropshofer H, Haring DA, Dahlke F, Patil A, Meinert R, Tomic D, Kappos L, Kuhle J. Blood Neurofilament Light in Progressive Multiple Sclerosis: Post Hoc Analysis of 2 Randomized Controlled Trials. Neurology. 2022 May 24;98(21):e2120-e2131. doi: 10.1212/WNL.0000000000200258. Epub 2022 Apr 4.

  PMID: 35379762 DERIVED

• Koch MW, Mostert J, Repovic P, Bowen JD, Strijbis E, Uitdehaag B, Cutter G. Smoking, obesity, and disability worsening in PPMS: an analysis of the INFORMS original trial dataset. J Neurol. 2022 Mar;269(3):1663-1669. doi: 10.1007/s00415-021-10750-z. Epub 2021 Aug 15.

  PMID: 34392376 DERIVED

• Koch MW, Mostert J, Zhang Y, Wolinsky JS, Lublin FD, Strijbis E, Cutter G. Association of Age With Contrast-Enhancing Lesions Across the Multiple Sclerosis Disease Spectrum. Neurology. 2021 Sep 28;97(13):e1334-e1342. doi: 10.1212/WNL.0000000000012603. Epub 2021 Aug 10.

  PMID: 34376508 DERIVED

• Miller DH, Lublin FD, Sormani MP, Kappos L, Yaldizli O, Freedman MS, Cree BAC, Weiner HL, Lubetzki C, Hartung HP, Montalban X, Uitdehaag BMJ, MacManus DG, Yousry TA, Gandini Wheeler-Kingshott CAM, Li B, Putzki N, Merschhemke M, Haring DA, Wolinsky JS. Brain atrophy and disability worsening in primary progressive multiple sclerosis: insights from the INFORMS study. Ann Clin Transl Neurol. 2018 Jan 30;5(3):346-356. doi: 10.1002/acn3.534. eCollection 2018 Mar.

  PMID: 29560379 DERIVED

• Lublin F, Miller DH, Freedman MS, Cree BAC, Wolinsky JS, Weiner H, Lubetzki C, Hartung HP, Montalban X, Uitdehaag BMJ, Merschhemke M, Li B, Putzki N, Liu FC, Haring DA, Kappos L; INFORMS study investigators. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016 Mar 12;387(10023):1075-1084. doi: 10.1016/S0140-6736(15)01314-8. Epub 2016 Jan 28.

  PMID: 26827074 DERIVED

• Hartung HP, Aktas O. Bleak prospects for primary progressive multiple sclerosis therapy: downs and downs, but a glimmer of hope. Ann Neurol. 2009 Oct;66(4):429-32. doi: 10.1002/ana.21880. No abstract available.

  PMID: 19847907 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Fingolimod Hydrochloride

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

trialandresults.registries@novartis.com

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 7, 2008
• First Posted: August 11, 2008
• Study Start: July 28, 2008
• Primary Completion: June 22, 2015
• Study Completion: June 22, 2015
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Locations

SE (2); AU (6); DK (2); FR (8); BE (6); US (33); CA (13); CZ (7); FI (3); IT (13); PL (4); HU (6); GB (9); DE (17); CH (5); ES (12); NL (6); TU (5)