Safety, Tolerability, Efficacy and Optimal Dose Finding Study of BAF312 in Patients With Relapsing-remitting Multiple Sclerosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00879658
First received: April 9, 2009
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

The purpose of this study is to determine the dose-response curve for the MRI-based efficacy of BAF312 compared with placebo in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), and to characterize its safety and tolerability for the selection of an optimal dose in a later phase III study.

Study Design Rationale An adaptive design was chosen to characterize the dose response curve of BAF312. In a first period of study ("Period 1"), three doses of BAF312 and placebo are tested for MRI efficacy. Based on an interim analysis (IA) after 3 months of treatment, two additional active doses for period 2 have been selected , thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. The doses are kept blinded. The use of Modeling and Simulation allows to establish the full range and dynamics of the dose-response curve in silico, and hence the definition of the optimal dose for later phase III studies.

The choice of placebo as treatment control is essential to obtain information on the specific compared to non-specific effects of active treatment and provides the best way of evaluating the efficacy and of assessing the true safety and tolerability profile of BAF312. Short-term placebo exposure (6 (Period 1) or 3 (Period 2) months, respectively) is unlikely to lead to longer term differences in outcomes [Polman, 2008]. The use of an adaptive design strategy contributes to a significant reduction of placebo exposure, both in terms of the number of patients and duration, as compared to conventional trial models.

Patients having completed the study within the protocol may be eligible for the Extension Phase study where they receive long-term BAF312 treatment (a separate protocol).


Condition Intervention Phase
Relapsing-remitting Multiple Sclerosis
Drug: BAF312
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase II, Double-blind, Randomized, Multi-center, Adaptive Dose-ranging, Placebo-controlled, Parallel-group Study Evaluating Safety, Tolerability and Efficacy on MRI Lesion Parameters and Determining the Dose Response Curve of BAF312 Given Orally Once Daily in Patients With Relapsing-remitting Multiple Sclerosis.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Dose response relationship among five doses of BAF312 and placebo during 3 months of treatment in patients with Relapsing-Remitting Multiple Sclerosis (RRMS), as measured by the number of combined unique active [MRI] lesions (CUAL). [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety and tolerability of BAF312 during 6 months and 3 months of treatment in MS patients [ Time Frame: 6 months, 3 months ] [ Designated as safety issue: Yes ]
  • To explore the effect of BAF312 on the number of relapses and thereof derived measures (e.g. annualized relapse rate (ARR), proportion of relapse-free patients) [ Time Frame: 6 months, 3 months ] [ Designated as safety issue: No ]
  • To explore the correlation of the course of the lymphocyte count with paraclinical measures (MRI activity) and with clinical course. [ Time Frame: 6 months, 3 months ] [ Designated as safety issue: No ]
  • To determine the effect of BAF312 after 3 months and 6 months treatment on additional MRI parameters [ Time Frame: 6 months, 3 months ] [ Designated as safety issue: No ]
  • To determine the steady state plasma concentrations of BAF312 in RRMS patients [ Time Frame: Month 1, Month 3, Month 6 ] [ Designated as safety issue: No ]

Enrollment: 296
Study Start Date: March 2009
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BAF312 10mg (period 1) Drug: BAF312
Experimental: BAF312 2 mg (period 1) Drug: BAF312
Experimental: BAF312 0.5 mg (period 1) Drug: BAF312
Experimental: BAF312 dose between 0.1 to 8 mg period 2 Drug: BAF312
Experimental: BAF312 dose between 0.1 - 8 mg period 2 Drug: BAF312
Placebo Comparator: Placebo (period 1, 2) Drug: Placebo

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Multiple Sclerosis (MS) as defined by revised McDonald criteria.
  • A relapsing-remitting course of disease with at least 1 documented relapse during the previous year, or 2 documented relapses during the previous 2 years, or a positive gadolinium (Gd)-enhanced MRI scan at screening (in case the first MRI scan obtained at screening is negative, a second scan may be obtained 1 month later.)
  • An Expanded Disability Status Scale (EDSS) score of 0-5.0 inclusive at randomization.
  • Neurologically stable with no evidence of relapse or corticosteroid treatment within 30 days prior to randomization.
  • Patients who decline initiation or continuation of treatment with available disease modifying drugs for MS, for whatever reason, after having been informed about their respective benefits and possible adverse events by the investigator.

Exclusion Criteria:

  • A manifestation of another type of MS than RRMS
  • History of chronic disease of the immune system other than MS
  • Malignancies, diabetes, significant cardiovascular, pulmonary and hepatic diseases and conditions
  • Active infections

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: NCT00879658

  Hide Study Locations
Locations
United States, Alabama
North Central Neurology Associates, PC
Cullman, Alabama, United States, 35058
United States, California
University of California San Francisco
San Francisco, California, United States, 94117
United States, Colorado
1st International
Centennial, Colorado, United States, 80112
United States, Florida
University of Miami Miller School of Medicine, Clinical Research Building
Miami, Florida, United States, 33136
Neurological Associates
Pompano Beach, Florida, United States, 33060
AMO Corporation
Tallahassee, Florida, United States, 32308
Axiom Clinical Research of Florida
Tampa, Florida, United States, 33609
United States, Illinois
University of Chicago, Department of Neurology
Chicago, Illinois, United States, 60637
Alexian Brothers Neurosciences Institute
Elk Grove Village, Illinois, United States, 60007
United States, Michigan
Michigan Medical, PC
Grand Rapids, Michigan, United States, 49525
United States, North Carolina
Raleigh Neurology Associates
Raleigh, North Carolina, United States, 27607
United States, Ohio
Neurology and Neuroscience Associates Inc.
Akron, Ohio, United States, 44302
United States, Pennsylvania
University of Pittsburgh Medical Center, Department of Neurology
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Absher Neurology
Greenville, South Carolina, United States, 29615
United States, Washington
Swedish Neuroscience Institute
Seattle, Washington, United States, 98122
United States, Wisconsin
Aurora St. Lukes Medical Center
Milwaukee, Wisconsin, United States, 53215
Canada, British Columbia
Novartis Investigative Site
Vancouver, British Columbia, Canada, V6T 2B5
Canada, Ontario
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Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
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Gatineau, Quebec, Canada, J9J 0A5
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Greenfield Park, Quebec, Canada, J4V 2J2
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Montreal, Quebec, Canada, H3A2B4
Finland
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Helsinki, Finland, FI-00100
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Tampere, Finland, FI-33520
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Turku, Finland, FI-20520
Germany
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Berlin, Germany, 10713
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Berlin, Germany, 13439
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Dresden, Germany, 01307
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Freiburg, Germany, 79106
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Leipzig, Germany, 04103
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Lengerich, Germany, 49525
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Munich, Germany, 81675
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Munster, Germany, 48149
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Wiesbaden, Germany, 65191
Hungary
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Budapest, Hungary, 1145
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Budapest, Hungary, 1076
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Debrecen, Hungary, 4012
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Veszprem, Hungary, 8200
Italy
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Chieti, Italy, 66100
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Milano, Italy, 20132
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Montichiari, Italy, 25018
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Roma, Italy, 00152
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Roma, Italy, 00133
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Roma, Italy, 00189
Norway
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Bergen, Norway, 5021
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Drammen, Norway, 3004
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Oslo, Norway, 0407
Poland
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Lodz, Poland, 90153
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Lublin, Poland, 20954
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Warsaw, Poland, 02957
Russian Federation
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Kazan, Russian Federation, 420103
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Moscow, Russian Federation, 127018
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Moscow, Russian Federation, 119049
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Moscow, Russian Federation, 125367
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Moscow, Russian Federation, 121359
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Moscow, Russian Federation, 119992
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Moscow, Russian Federation, 129110
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St Petersburg, Russian Federation, 197022
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St Petersburg, Russian Federation, 197376
Spain
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Barcelona, Spain, 08035
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Bilbao, Spain, 48013
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Sevilla, Spain, 41009
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Valencia, Spain, 46009
Switzerland
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Basel, Switzerland, 4031
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Bern, Switzerland, 3010
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Lugano, Switzerland, 6900
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Zurich, Switzerland, 8091
Turkey
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Ankara, Turkey, 06100
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Haseki/Istanbul, Turkey
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Istanbul, Turkey, 34668
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Izmir, Turkey, 35340
Novartis Investigative Site
Kocaeli, Turkey, 41380
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00879658     History of Changes
Other Study ID Numbers: CBAF312A2201, 2008-008719-25
Study First Received: April 9, 2009
Last Updated: September 19, 2012
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Finland: Finnish Medicines Agency
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Norway: Norwegian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Russia: Ministry of Health of the Russian Federation
Spain: Spanish Agency of Medicines
Switzerland: Swissmedic
Turkey: Ministry of Health

Keywords provided by Novartis:
Multiple Sclerosis
Relapsing-Remitting
Demyelinating Autoimmune Diseases

Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on July 22, 2014