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

April 9, 2009
September 19, 2012
March 2009
May 2011   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00879658 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Safety and tolerability (including blood pressure effects) 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 (MRI activity) and clinical course. [ Time Frame: 6 months, 3 months ] [ Designated as safety issue: No ]
  • To determine the effect of BAF312 at 6 and 3 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 ]
Not Provided
Not Provided
 
Safety, Tolerability, Efficacy and Optimal Dose Finding Study of BAF312 in Patients With Relapsing-remitting Multiple Sclerosis
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.

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).

Not Provided
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Relapsing-remitting Multiple Sclerosis
  • Drug: BAF312
  • Drug: Placebo
  • Experimental: BAF312 10mg (period 1)
    Intervention: Drug: BAF312
  • Experimental: BAF312 2 mg (period 1)
    Intervention: Drug: BAF312
  • Experimental: BAF312 0.5 mg (period 1)
    Intervention: Drug: BAF312
  • Experimental: BAF312 dose between 0.1 to 8 mg period 2
    Intervention: Drug: BAF312
  • Experimental: BAF312 dose between 0.1 - 8 mg period 2
    Intervention: Drug: BAF312
  • Placebo Comparator: Placebo (period 1, 2)
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
296
May 2011
May 2011   (final data collection date for primary outcome measure)

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

Both
18 Years to 55 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Poland,   Switzerland,   Turkey,   Canada,   Finland,   Germany,   Hungary,   Italy,   Norway,   Russian Federation,   Spain
 
NCT00879658
CBAF312A2201, 2008-008719-25
Not Provided
Novartis ( Novartis Pharmaceuticals )
Novartis Pharmaceuticals
Not Provided
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Novartis
September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP