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

NCT ID: NCT00879658

Last Updated: 2020-01-13

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

297 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-30

Study Completion Date

2011-05-04

Brief Summary

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The purpose of this study was 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 were tested for MRI efficacy. Based on an interim analysis (IA) after 3 months of treatment, two additional active doses for period 2 wereselected , thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. The doses were kept blinded. The use of Modeling and Simulation allowed 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 was 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) was unlikely to lead to longer term differences in outcomes \[Polman, 2008\]. The use of an adaptive design strategy contributed 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 might be eligible for the Extension Phase study where they receive long-term BAF312 treatment (a separate protocol).

Detailed Description

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Conditions

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Relapsing-remitting Multiple Sclerosis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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BAF312 10mg (period 1)

Group Type EXPERIMENTAL

BAF312

Intervention Type DRUG

BAF312 2 mg (period 1)

Group Type EXPERIMENTAL

BAF312

Intervention Type DRUG

BAF312 0.5 mg (period 1)

Group Type EXPERIMENTAL

BAF312

Intervention Type DRUG

BAF312 dose between 0.1 to 8 mg period 2

Group Type EXPERIMENTAL

BAF312

Intervention Type DRUG

BAF312 dose between 0.1 - 8 mg period 2

Group Type EXPERIMENTAL

BAF312

Intervention Type DRUG

Placebo (period 1, 2)

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Interventions

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BAF312

Intervention Type DRUG

Placebo

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Novartis Investigative Site

Cullman, Alabama, United States

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San Francisco, California, United States

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Centennial, Colorado, United States

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Miami, Florida, United States

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Pompano Beach, Florida, United States

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Tallahassee, Florida, United States

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Tampa, Florida, United States

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Chicago, Illinois, United States

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Elk Grove Village, Illinois, United States

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Grand Rapids, Michigan, United States

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Raleigh, North Carolina, United States

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Akron, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Greenville, South Carolina, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Vancouver, British Columbia, Canada

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Ottawa, Ontario, Canada

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Gatineau, Quebec, Canada

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Greenfield Park, Quebec, Canada

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Montreal, Quebec, Canada

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Helsinki, , Finland

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Tampere, , Finland

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Turku, , Finland

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Berlin, , Germany

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Berlin, , Germany

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Dresden, , Germany

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Freiburg im Breisgau, , Germany

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Leipzig, , Germany

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Lengerich, , Germany

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München, , Germany

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Münster, , Germany

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Wiesbaden, , Germany

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Budapest, , Hungary

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Budapest, , Hungary

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Debrecen, , Hungary

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Veszprém, , Hungary

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Montichiari, BS, Italy

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Chieti, CH, Italy

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Milan, MI, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Roma, RM, Italy

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Bergen, , Norway

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Drammen, , Norway

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Oslo, , Norway

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Lodz, , Poland

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Lublin, , Poland

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Warsaw, , Poland

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Kazan', , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Moscow, , Russia

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Saint Petersburg, , Russia

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Saint Petersburg, , Russia

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Seville, Andalusia, Spain

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Bilbao, Basque Country, Spain

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Barcelona, Catalonia, Spain

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Valencia, Valencia, Spain

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Madrid, , Spain

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Basel, , Switzerland

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Bern, , Switzerland

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Lugano, , Switzerland

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Zurich, , Switzerland

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Ankara, , Turkey (Türkiye)

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Haseki / Istanbul, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Kocaeli, , Turkey (Türkiye)

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Countries

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United States Canada Finland Germany Hungary Italy Norway Poland Russia Spain Switzerland Turkey (Türkiye)

References

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Mercier F, Bornkamp B, Ohlssen D, Wallstroem E. Characterization of dose-response for count data using a generalized MCP-Mod approach in an adaptive dose-ranging trial. Pharm Stat. 2015 Jul-Aug;14(4):359-67. doi: 10.1002/pst.1693. Epub 2015 Jun 17.

Reference Type DERIVED
PMID: 26083135 (View on PubMed)

Selmaj K, Li DK, Hartung HP, Hemmer B, Kappos L, Freedman MS, Stuve O, Rieckmann P, Montalban X, Ziemssen T, Auberson LZ, Pohlmann H, Mercier F, Dahlke F, Wallstrom E. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013 Aug;12(8):756-67. doi: 10.1016/S1474-4422(13)70102-9. Epub 2013 Jun 11.

Reference Type DERIVED
PMID: 23764350 (View on PubMed)

Other Identifiers

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2008-008719-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CBAF312A2201

Identifier Type: -

Identifier Source: org_study_id

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