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

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00879658

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 (including effects on blood pressure) for the selection of an optimal dose in a later phase III study.

An adaptive design was chosen to characterize the dose response curve of BAF312 with 5 active treatment arms and placebo. Currently only treatment arms for the first period of the study are posted. The treatment arms for period 2 will be added after the results of the interim analysis are available (expected early 2010).

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 doses are selected for another group of patients in a following second period ("Period 2"), thus allowing to optimize the overall determination of the dose response curve with 5 data points of active treatment, and placebo. 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 versus 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 placebo exposure [6 (Period 1) or 3 (Period 2) months, respectively] does not 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 their treatment within the protocol of this study are 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 10mg Drug: BAF312 2 mg Drug: BAF312 0.5 mg Drug: Placebo	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Parallel Assignment
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:

MedlinePlus related topics: Autoimmune Diseases Multiple Sclerosis

U.S. FDA Resources

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 (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 ]

Estimated Enrollment:	275
Study Start Date:	March 2009
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1 (period 1): Experimental	Drug: BAF312 10mg
2 (period 1): Experimental	Drug: BAF312 2 mg
3 (period 1): Experimental	Drug: BAF312 0.5 mg
4 (period 1): Placebo Comparator	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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00879658

Contacts

Contact: Novartis Pharmaceuticals

+41-61-324-1111

Show 82 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	Novartis Pharmaceuticals ( External Affairs )
Study ID Numbers:	CBAF312A2201, EudraCT 2008-008719-25
Study First Received:	April 9, 2009
Last Updated:	September 2, 2009
ClinicalTrials.gov Identifier:	NCT00879658 History of Changes
Health Authority:	Canada: Health Canada; Finland: National Agency for Medicines; 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 and Social Development of the Russian Federation; Spain: Spanish Agency of Medicines; United States: Food and Drug Administration; Switzerland: Swissmedic; Turkey: Ministry of Health

Keywords provided by Novartis:

Multiple Sclerosis
Relapsing-Remitting
Demyelinating Autoimmune Diseases

Additional relevant MeSH terms:

Pathologic Processes
Autoimmune Diseases
Multiple Sclerosis
Immune System Diseases
Demyelinating Diseases

Nervous System Diseases
Demyelinating Autoimmune Diseases, CNS
Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Autoimmune Diseases of the Nervous System

ClinicalTrials.gov processed this record on November 05, 2009