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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00879658
Recruitment Status : Completed
First Posted : April 10, 2009
Last Update Posted : March 2, 2018
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:

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 or disease Intervention/treatment Phase
Relapsing-remitting Multiple Sclerosis Drug: BAF312 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 296 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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.
Study Start Date : March 2009
Primary Completion Date : May 2011
Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Safety and tolerability of BAF312 during 6 months and 3 months of treatment in MS patients [ Time Frame: 6 months, 3 months ]
  2. 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 ]
  3. 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 ]
  4. To determine the effect of BAF312 after 3 months and 6 months treatment on additional MRI parameters [ Time Frame: 6 months, 3 months ]
  5. To determine the steady state plasma concentrations of BAF312 in RRMS patients [ Time Frame: Month 1, Month 3, Month 6 ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00879658

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Sponsors and Collaborators
Novartis Pharmaceuticals
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals Identifier: NCT00879658     History of Changes
Other Study ID Numbers: CBAF312A2201
2008-008719-25 ( EudraCT Number )
First Posted: April 10, 2009    Key Record Dates
Last Update Posted: March 2, 2018
Last Verified: February 2018

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Multiple Sclerosis
Demyelinating Autoimmune Diseases

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