FTY720 in Patients With Primary Progressive Multiple Sclerosis

Primary Progressive Multiple Sclerosis Clinical Trial

— INFORMS  

Official title:

A Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5mg FTY720 Administered Orally Once Daily Versus Placebo in Patients With Primary Progressive Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00731692
• Other study ID #: CFTY720D2306
• Secondary ID: 2007-002627-32
• Status: Completed
• Phase: Phase 3
• First received: August 7, 2008
• Last updated: April 13, 2015
• Start date: July 2008
• Est. completion date: December 2014

Study information

• Verified date: April 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationAustralia: Department of Health and Ageing Therapeutic Goods AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsCanada: Health CanadaCzech Republic: State Institute for Drug ControlDenmark: Danish Medicines AgencyEuropean Union: European Medicines AgencyFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencyNetherlands: Medicines Evaluation Board (MEB)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsSpain: Spanish Agency of MedicinesSweden: Medical Products AgencySwitzerland: SwissmedicUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 969
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 25 Years to 65 Years

Eligibility

Inclusion Criteria:

General

1. sign written informed consent prior to participating in the study

2. 25 through 65 years of age inclusive

3. 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.

1. diagnosis of primary progressive multiple sclerosis (according to the 2005 Revised McDonald criteria):

2. time since first reported symptoms between 2 and 10 years

3. evidence of clinical disability progression in the 2 years prior to Screening

4. disability status at Screening

• EDSS score of 3.5-6.0 inclusive

• pyramidal functional system score of 2 or more

• 25'TWT less than 30 seconds

Exclusion Criteria:

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

• History or presence of second and third degree AV block or an increase QT interval (QTc>440 ms)

• Arrythmia requiring treatment with class III antiarrythmic drugs

• History of positive tilt test from workout of vasovagal syncope

• Hypertension, not controlled with medication

Pulmonary:

• Severe respiratory disease or pulmonary fibrosis

• TB

• Abnormal X-ray, suggestive of active pulmonary disease

• Abnormal PFT: <70% of predicted for FEV1 and FVC; <60% for DLCO

• Patients receiving chronic (daily) therapies for asthma

Hepatic:

• Known history of alcohol abuse, chronic liver or biliary disease

• Total or conjugated Brb >ULN, unless in context of Gilbert's syndrome

• AP >1.5xULN; ALT/AST >2xULN; GGT>3xULN

Other:

• History of chronic disease of the immune system other than MS

• Malignancy (other than successfully treated SCC or BCC)

• Diabetes Mellitus

• Macular Edema present at screening

• HIV, Hepatitis C or B, other active infection

• History of total lymphoid irradiation or bone marrow transplantation

• Serum creatinine >1.7 mg/dl

• WBC <3500 cells/mm3

• Lymphocyte count <800 cells/mm3

• History of substance abuse or any other factor that may interfere with subject ability to cooperate and comply with the study procedures

• Unable to undergo MRI scans

• Participation in any therapeutical clinical research study in the 6 months prior to randomization

• Pregnant or lactating women

• Drugs requiring wash-out period:

3 months:

• Systemic corticosteroids or ACTH

• INF-beta

6 months:

• Immunosuppressive medication

• Immunoglobulins

• Monoclonal antibodies

• Drugs that exclude participation in the study:

• Cladribine

• Cyclophosphamide

• Mitoxantrone (except: patients who received a cumulative dose of no more than 60mg/m2 more than 5 years ago could enter the study)

Other protocol-defined inclusion/exclusion criteria may apply.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Primary Progressive Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• FTY720

• Placebo
Capsules

Locations

Country	Name	City	State
Australia	Novartis Investigative Site	Box Hill	Victoria
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Hobart	Tasmania
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	Parkville	Victoria
Belgium	Novartis Investigative Site	Charleroi
Belgium	Novartis Investigative Site	Edegem
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Liege
Belgium	Novartis Investigative Site	Melsbroek
Belgium	Novartis Investigative Site	Sint-Truiden
Canada	Novartis Investigative Site	Burnaby	British Columbia
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Regina	Saskatchewan
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
Canada	Novartis Investigative Site	Vancouver	British Columbia
Czech Republic	Novartis Investigative Site	Brno
Czech Republic	Novartis Investigative Site	Olomouc	CZE
Czech Republic	Novartis Investigative Site	Ostrava-Poruba
Czech Republic	Novartis Investigative Site	Plzen
Czech Republic	Novartis Investigative Site	Praha 2
Czech Republic	Novartis Investigative Site	Rychnov nad Kneznou
Czech Republic	Novartis Investigative Site	Teplice
Denmark	Novartis Investigative Site	Aarhus
Denmark	Novartis Investigative Site	Glostrup
Denmark	Novartis Investigative Site	Sønderborg
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Tampere
Finland	Novartis Investigative Site	Turku
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Lille Cedex
France	Novartis Investigative Site	Marseille cedex 05
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nantes Cedex 1
France	Novartis Investigative Site	Paris Cedex 13
France	Novartis Investigative Site	Rennes
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Düsseldorf
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Essen
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hennigsdorf
Germany	Novartis Investigative Site	Magdeburg
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	München
Germany	Novartis Investigative Site	Teupitz
Germany	Novartis Investigative Site	Trier
Germany	Novartis Investigative Site	Würzburg
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Gyor
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Veszprem
Italy	Novartis Investigative Site	Bari	BA
Italy	Novartis Investigative Site	Catania	CT
Italy	Novartis Investigative Site	Cefalù	PA
Italy	Novartis Investigative Site	Chieti	CH
Italy	Novartis Investigative Site	Gallarate	VA
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Montichiari	BS
Italy	Novartis Investigative Site	Orbassano	TO
Italy	Novartis Investigative Site	Padova	PD
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Nieuwegein
Netherlands	Novartis Investigative Site	Nijmegen
Netherlands	Novartis Investigative Site	Sittard-Geleen
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Poland	Novartis Investigative Site	Warszawa
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	Girona	Catalunya
Spain	Novartis Investigative Site	L'Hospitalet de Llobregat	Catalunya
Spain	Novartis Investigative Site	Lleida	Catalunya
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Majadahonda	Madrid
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Sweden	Novartis Investigative Site	Göteborg
Sweden	Novartis Investigative Site	Stockholm
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Bern
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Atakum / Samsun
Turkey	Novartis Investigative Site	Balcova / Izmir
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Yenisehir / Izmir
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Norwich
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Sheffield
United States	Novartis Investigative Site	Atlanta	Georgia
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Boston	Massachusetts
United States	Novartis Investigative Site	Brookline	Massachusetts
United States	Novartis Investigative Site	Buffalo	New York
United States	Novartis Investigative Site	Burlington	Vermont
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Charlottesville	Virginia
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Cleveland	Ohio
United States	Novartis Investigative Site	Columbus	Ohio
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Durham	North Carolina
United States	Novartis Investigative Site	Houston	Texas
United States	Novartis Investigative Site	Kansas City	Kansas
United States	Novartis Investigative Site	Knoxville	Tennessee
United States	Novartis Investigative Site	Madison	Wisconsin
United States	Novartis Investigative Site	Nashville	Tennessee
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Newport Beach	California
United States	Novartis Investigative Site	Pittsburgh	Pennsylvania
United States	Novartis Investigative Site	Pompano Beach	Florida
United States	Novartis Investigative Site	Rochester	New York
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	St. Louis	Missouri
United States	Novartis Investigative Site	Stony Brook	New York
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Hungary,  Italy,  Netherlands,  Poland,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate the effect of FTY720 relative to placebo on delaying the time to sustained disability progression for patients treated for at least 36 months		When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study	No
Secondary	To evaluate the safety and tolerability of FTY720 compared to placebo in patients with PPMS		when the last patient still ongoing in the study completes Month 36 of the double blind treatment phase	Yes
Secondary	To evaluate the effect of FTY720 relative to placebo on conventional MRI parameters		When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study	No
Secondary	To evaluate the effect of FTY720 relative to placebo on Patient Reported Outcomes		When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study	No