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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00731692




Registration number
NCT00731692
Ethics application status
Date submitted
7/08/2008
Date registered
11/08/2008

Titles & IDs
Public title
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.
Scientific title
A Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of 0.5mg Fingolimod Administered Orally Once Daily Versus Placebo in Patients With Primary Progressive Multiple Sclerosis and An Open-label, Single-arm Extension Study to the Double-blind, Randomized, Multicenter, Placebo-controlled, Parallel-group Study Comparing the Efficacy and Safety of0.5 mg FTY720 Administered Orally Once Daily Versus Placebo in Patients With Primary Progressive Multiple Sclerosis
Secondary ID [1] 0 0
2007-002627-32
Secondary ID [2] 0 0
CFTY720D2306
Universal Trial Number (UTN)
Trial acronym
INFORMS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary Progressive Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - FTY720
Treatment: Drugs - Placebo

Experimental: FTY720D 0.5 mg - Cohort 2: The 0.5 mg group consists of patients who were directly randomized to fingolimod 0.5 mg (i.e. AFTER the amendment

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

Experimental: FTY720D 1.25 mg switch to 0.5 mg - 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


Treatment: Drugs: FTY720
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

Treatment: Drugs: Placebo
Matching placebo capsules were administered orally once daily

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Kaplan-Meier Estimate of the Risk of 3-month Confirmed Disability Progression Based on Composite Endpoint
Timepoint [1] 0 0
up to 36 months after the last patient was randomized
Secondary outcome [1] 0 0
Kaplan-Meier Estimate of the Risk of 3- Month Confirmed Disability Progression Based on Expanded Disability Status Scale (EDSS)
Timepoint [1] 0 0
up to 36 months after the last patient was randomized
Secondary outcome [2] 0 0
Percent Change From Baseline in Brain Volume at Month 36
Timepoint [2] 0 0
Baseline to month 36
Secondary outcome [3] 0 0
Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 9-HPT.
Timepoint [3] 0 0
up to 36 months after the last patient was randomized
Secondary outcome [4] 0 0
Kaplan Meier Estimate -Percentage of Participants With 3- Month Confirmed Disability Progression Based on 25' TWT.
Timepoint [4] 0 0
up to 36 months after the last patient was randomized
Secondary outcome [5] 0 0
Number of New/Enlarging T2 Lesions Per Year Measured From Baseline to Month 36
Timepoint [5] 0 0
Baseline to 36 months
Secondary outcome [6] 0 0
Number of Gd-enhancing Lesions at Month 36
Timepoint [6] 0 0
Baseline to 36 months
Secondary outcome [7] 0 0
Percent Change in Total T2 Lesion Volume From Baseline to Month 36
Timepoint [7] 0 0
Baseline to month 36
Secondary outcome [8] 0 0
Change From Baseline in the Patient Reported Indices in Multiple Sclerosis (PRIMUS-QoL Score)
Timepoint [8] 0 0
Baseline, 36 months
Secondary outcome [9] 0 0
Change From Baseline in PRIMUS-Activities
Timepoint [9] 0 0
Baseline, 36 months
Secondary outcome [10] 0 0
Change From Baseline in Unidimensional Fatigue Impact (U-FIS) Score
Timepoint [10] 0 0
Baseline, 36 months
Secondary outcome [11] 0 0
Change From Baseline in European Quality of Life - 5 Dimensions (EQ-5D Score)
Timepoint [11] 0 0
Baseline, 36 months
Secondary outcome [12] 0 0
Change From Baseline in Multiple Sclerosis Walking Scale (MSWS-12 Score)
Timepoint [12] 0 0
Baseline, 36 months
Secondary outcome [13] 0 0
Blood Concentrations of Fingolimod and Fingolimod-phosphate
Timepoint [13] 0 0
Month 3 up to 36 months
Secondary outcome [14] 0 0
Change in MSFC Z-score and Subscale Scores From Baseline to Month 36
Timepoint [14] 0 0
Baseline to Month 36

Eligibility
Key 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

Extension study Inclusion criteria

* 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.
* Patients initially randomized to fingolimod 0.5 mg or placebo as part of the second study cohort, were to have continued on study drug treatment until such time as the last ongoing patient enrolled in the study had reached 3 years in study
Minimum age
25 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Extension study Exclusion criteria

-Patients were not eligible for enrollment in the extension study if they had any of the following key exclusion criteria at the extension study Baseline visit: active chronic immune system disease other than MS (or stable disease treated with immune therapy); known immunodeficiency syndrome; active infection; uncontrolled diabetes mellitus; macularedema; treatment with Class Ia or III antiarrhythmic drugs; any of the specified cardiac, pulmonary, or hepatic conditions; or any medically unstable condition

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,TAS,VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Camperdown
Recruitment hospital [2] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [3] 0 0
Novartis Investigative Site - Hobart
Recruitment hospital [4] 0 0
Novartis Investigative Site - Box Hill
Recruitment hospital [5] 0 0
Novartis Investigative Site - Heidelberg
Recruitment hospital [6] 0 0
Novartis Investigative Site - Parkville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3084 - Heidelberg
Recruitment postcode(s) [6] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Illinois
Country [6] 0 0
United States of America
State/province [6] 0 0
Kansas
Country [7] 0 0
United States of America
State/province [7] 0 0
Maryland
Country [8] 0 0
United States of America
State/province [8] 0 0
Massachusetts
Country [9] 0 0
United States of America
State/province [9] 0 0
Michigan
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New Jersey
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
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United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
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Texas
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United States of America
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Vermont
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United States of America
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Virginia
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United States of America
State/province [20] 0 0
Washington
Country [21] 0 0
United States of America
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Wisconsin
Country [22] 0 0
Belgium
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Charleroi
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Belgium
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Edegem
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Belgium
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Leuven
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Belgium
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Liege
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Belgium
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Melsbroek
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Belgium
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Sint-Truiden
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Canada
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Alberta
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Canada
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British Columbia
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Canada
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Nova Scotia
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Canada
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Ontario
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Canada
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Quebec
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Canada
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Saskatchewan
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Czechia
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Czech Republic
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Czechia
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CZE
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Czechia
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Ostrava-Poruba
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Plzen
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Praha 2
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Czechia
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Teplice
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Aarhus
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Sønderborg
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Finland
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Helsinki
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Finland
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Tampere
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Turku
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France
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Bordeaux Cedex
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France
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Lille Cedex
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France
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Marseille cedex 05
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France
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Montpellier
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France
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Nantes Cedex 1
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France
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Paris Cedex 13
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France
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Rennes
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France
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Strasbourg
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Germany
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Berlin
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Germany
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Bochum
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Dresden
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Duesseldorf
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Erlangen
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Essen
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Freiburg
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Germany
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Hannover
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Germany
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Hennigsdorf
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Magdeburg
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Germany
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Muenchen
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Germany
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Muenster
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Germany
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Munchen
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Teupitz
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Trier
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Würzburg
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Hungary
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Budapest
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Debrecen
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Gyor
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Miskolc
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Veszprem
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Italy
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BA
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Italy
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BS
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Italy
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CH
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Italy
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CT
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Italy
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GE
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Italy
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MI
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Italy
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PA
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Italy
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PD
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Italy
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RM
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Italy
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TO
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Italy
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VA
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Netherlands
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CK
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Netherlands
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Amsterdam
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Eindhoven
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Nieuwegein
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Netherlands
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Nijmegen
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Netherlands
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Sittard-Geleen
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Poland
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Lodz
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Poland
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Lublin
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Poland
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Warszawa
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Spain
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Andalucia
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Spain
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Madrid
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Spain
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Pais Vasco
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Sweden
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Goeteborg
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Sweden
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Stockholm
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Switzerland
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Basel
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Switzerland
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Bern
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Switzerland
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Lausanne
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Switzerland
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Lugano
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Switzerland
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Zuerich
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Turkey
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Ankara
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Turkey
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Atakum / Samsun
Country [108] 0 0
Turkey
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Balcova / Izmir
Country [109] 0 0
Turkey
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Istanbul
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Turkey
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Yenisehir / Izmir
Country [111] 0 0
United Kingdom
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Manchester
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United Kingdom
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South Yorkshire
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Bristol
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London
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United Kingdom
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Newcastle Upon Tyne
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United Kingdom
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Norwich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.