Clinical trial NCT01185821: Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis
Official title: A Dose Blinded Extension Study to the CBAF312A2201 Study to Evaluate Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally Once Daily in Patients With Relapsing-remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: BAF312
siponimod
Multiple Sclerosis
Relapsing remitting Multiple Sclerosis
Demyelinating Autoimmune Diseases
MS
RRMS
inflammatory disease
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2010-08-20
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Maximum age (years): 56
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This extension study was originally set up as a 2 year dose-blinded extension study to maintain blinding of ongoing Core study. Study was later amended to include a subsequent Open-Label treatment phase after Core study was unblinded. During the Dose-Blinded phase of the extension study patients received the same dose from the Core study. Patients who received placebo in Period 1 during the Core Study were equally randomized to 1 of the 3 active doses of siponimod used during Period 1 (0.5, 2.0, or 10 mg) and patients who received placebo in Period 2 were equally randomized to 1 of the 2 active doses of siponimod used during Period 2 (0.25 mg or 1.25 mg).
Primary purpose: TREATMENT

Brief summary: This study consisted of a two year dose blinded phase during which patients received one of five doses of siponimod (10, 2, 1.25, 0.5 or 0.25mg) following which patients were switched to open label treatment with siponimod 2mg for approximately a further 3 years. It will provide data on long term safety, tolerability and efficacy of siponimod in the RRMS patient population

Detailed description: This study was prematurely discontinued after approximately 5 years. The decision to prematurely discontinue the study was not taken due to safety-related concerns, rather due to a decision to focus the development of siponimod in MS on a different population.

Eligibility criteria: Inclusion Criteria:

* Patients completed the core study BAF312A2201
* Written informed consent provided before any assessment of the extension study
* Female patients at risk of becoming pregnant must have a negative pregnancy test and use simultaneously two forms of effective contraception

Exclusion Criteria:

* Newly diagnosed systemic disease other than MS (which may require immunosuppressive treatment)
* Malignancies, diabetes, significant cardiovascular and pulmonary diseases and conditions
* Active infections

Primary outcomes:
measure: Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study.
timeFrame: Baseline up to approximately 5 years
measure: Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout)
timeFrame: Baseline Extension up to day 10
measure: Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout)
timeFrame: Baseline Extension up to day 10
measure: Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set)
timeFrame: Baseline Extension up to approximately 5 years
measure: Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set)
timeFrame: Baseline Extension up to approximately 5 years
measure: Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set)
timeFrame: Baseline Extension up to approximately 5 years
Secondary outcomes:
measure: Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set)
timeFrame: Baseline extension up to approximately 5 years
measure: Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set)
timeFrame: Baseline Extension up to approximately 5 years
measure: Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set)
timeFrame: Baseline Extension up to approximately 5 years
Other outcomes:
Locations:
city: Miami
country: United States
facility: Novartis Investigative Site
state: Florida
city: Pompano Beach
country: United States
facility: Novartis Investigative Site
state: Florida
city: Tallahassee
country: United States
facility: Novartis Investigative Site
state: Florida
city: Chicago
country: United States
facility: Novartis Investigative Site
state: Illinois
city: Grand Rapids
country: United States
facility: Novartis Investigative Site
state: Michigan
city: Akron
country: United States
facility: Novartis Investigative Site
state: Ohio
city: Greenville
country: United States
facility: Novartis Investigative Site
state: South Carolina
city: Seattle
country: United States
facility: Novartis Investigative Site
state: Washington
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Gatineau
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Greenfield Park
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Helsinki
country: Finland
facility: Novartis Investigative Site
city: Tampere
country: Finland
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Ibbenbueren
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Muenster
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Veszprem
country: Hungary
facility: Novartis Investigative Site
city: Montichiari
country: Italy
facility: Novartis Investigative Site
state: BS
city: Chieti
country: Italy
facility: Novartis Investigative Site
state: CH
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Roma
country: Italy
facility: Novartis Investigative Site
state: RM
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Oslo
country: Norway
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Lublin
country: Poland
facility: Novartis Investigative Site
city: Warszawa
country: Poland
facility: Novartis Investigative Site
city: Kazan
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Saint-Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Sevilla
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Valencia
country: Spain
facility: Novartis Investigative Site
state: Comunidad Valenciana
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: Lugano
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Haseki / Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Izmir
country: Turkey
facility: Novartis Investigative Site
city: Kocaeli
country: Turkey
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Kappos L, Li DK, Stuve O, Hartung HP, Freedman MS, Hemmer B, Rieckmann P, Montalban X, Ziemssen T, Hunter B, Arnould S, Wallstrom E, Selmaj K. Safety and Efficacy of Siponimod (BAF312) in Patients With Relapsing-Remitting Multiple Sclerosis: Dose-Blinded, Randomized Extension of the Phase 2 BOLD Study. JAMA Neurol. 2016 Sep 1;73(9):1089-98. doi: 10.1001/jamaneurol.2016.1451.