FTY720 in Patients With Primary Progressive Multiple Sclerosis (INFORMS)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00731692
First received: August 7, 2008
Last updated: May 21, 2014
Last verified: May 2014
  Purpose

The purpose of this study is to evaluate whether FTY720 is effective in delaying MS disability progression compared to placebo in patients with PPMS.


Condition Intervention Phase
Primary Progressive Multiple Sclerosis
Drug: FTY720
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • 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 [ Time Frame: When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of FTY720 compared to placebo in patients with PPMS [ Time Frame: when the last patient still ongoing in the study completes Month 36 of the double blind treatment phase ] [ Designated as safety issue: Yes ]
  • To evaluate the effect of FTY720 relative to placebo on conventional MRI parameters [ Time Frame: When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study ] [ Designated as safety issue: No ]
  • To evaluate the effect of FTY720 relative to placebo on Patient Reported Outcomes [ Time Frame: When the last still ongoing patient in the double-blind treatment phase completes Month 36 of the study ] [ Designated as safety issue: No ]

Enrollment: 969
Study Start Date: July 2008
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: FTY720D 0.5 mg Drug: FTY720
Placebo Comparator: Placebo Drug: Placebo
Capsules

  Eligibility

Ages Eligible for Study:   25 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00731692

  Show 157 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00731692     History of Changes
Other Study ID Numbers: CFTY720D2306, 2007-002627-32
Study First Received: August 7, 2008
Last Updated: May 21, 2014
Health Authority: United States: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
Czech Republic: State Institute for Drug Control
Denmark: Danish Medicines Agency
European Union: European Medicines Agency
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Netherlands: Medicines Evaluation Board (MEB)
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
FTY720, primary progressive multiple sclerosis,PPMS

Additional relevant MeSH terms:
Fingolimod
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Sclerosis
Autoimmune Diseases
Autoimmune Diseases of the Nervous System
Demyelinating Autoimmune Diseases, CNS
Demyelinating Diseases
Immune System Diseases
Nervous System Diseases
Pathologic Processes
Immunologic Factors
Immunosuppressive Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 23, 2014