Long-term Safety, Tolerability and Efficacy of BAF312 Given Orally in Patients With Relapsing-remitting Multiple Sclerosis

Relapsing Remitting Multiple Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01185821
• Other study ID #: CBAF312A2201E1
• Secondary ID: 2009-014392-51
• Status: Completed
• Phase: Phase 2
• First received: August 19, 2010
• Last updated: February 27, 2018
• Start date: August 30, 2010
• Est. completion date: October 10, 2016

Study information

• Verified date: February 2018
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: October 10, 2016
• Est. primary completion date: October 10, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 56 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• BAF312
BAF312 was supplied in film-coated tablets in strengths of 5, 4 ,2, 1, .5 and .25 mg. The actual doses taken were 10, 2, 1.25, .5 and .25 mg taken orally once a day.

Locations

Country	Name	City	State
Canada	Novartis Investigative Site	Gatineau	Quebec
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Finland	Novartis Investigative Site	Helsinki
Finland	Novartis Investigative Site	Tampere
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Ibbenbueren
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Debrecen
Hungary	Novartis Investigative Site	Veszprem
Italy	Novartis Investigative Site	Chieti	CH
Italy	Novartis Investigative Site	Montichiari	BS
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Norway	Novartis Investigative Site	Bergen
Norway	Novartis Investigative Site	Oslo
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Lublin
Poland	Novartis Investigative Site	Warszawa
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	Saint-Petersburg
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigative Site	Ankara
Turkey	Novartis Investigative Site	Haseki / Istanbul
Turkey	Novartis Investigative Site	Istanbul
Turkey	Novartis Investigative Site	Izmir
Turkey	Novartis Investigative Site	Kocaeli
United States	Novartis Investigative Site	Akron	Ohio
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Grand Rapids	Michigan
United States	Novartis Investigative Site	Greenville	South Carolina
United States	Novartis Investigative Site	Miami	Florida
United States	Novartis Investigative Site	Pompano Beach	Florida
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Tallahassee	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Canada,  Finland,  Germany,  Hungary,  Italy,  Norway,  Poland,  Russian Federation,  Spain,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study.	Refer to adverse events for complete listing of serious adverse events and other adverse events. Adverse events of interest were presented in separate tables. There were no reports of macular edema.	Baseline up to approximately 5 years
Primary	Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout)	Number of patients with abnormal ECG conduction findings during dose-blinded titration at any visit post-dose, by type of abnormality and treatment (Extension Set). Number analyzed represent participants who had ECG results. Washout was defined as not being on treatment drug between Core and Extension for >7 days. Abbreviation: Con=conduction, IVCD=intraventricular conduction defect , WPW=Wolff-Parkinson-White syndrome	Baseline Extension up to day 10
Primary	Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout)	Number of patients with abnormal ECG conduction findings during dose-blinded titration at any visit post-dose, by type of abnormality and treatment (Extension Set). Number analyzed represent participants who had ECG results. Washout was defined as not being on treatment drug between Core and Extension for >7 days. Abbreviations: washout = WO, Con=conduction	Baseline Extension up to day 10
Primary	Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set)	Sitting blood pressure was measured in triplicate. The categories of notably low and high values and changes are presented for systolic (SBP) and diastolic (DBP). Multiple occurrences for a patient are counted as one occurrence in this table.	Baseline Extension up to approximately 5 years
Primary	Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set)	Most infections were clinical diagnoses and were not confirmed by microbiology / virologic investigations. A patient with multiple occurrences of an infection for a preferred term is counted only once in each specific category.; Events identified as infections by the Investigator and defined as an AE with onset on or after the first dose of Extension Study drug up to and including 30 days after the date of the last dose	Baseline Extension up to approximately 5 years
Primary	Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set)		Baseline Extension up to approximately 5 years
Secondary	Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set)	Group level ARR (raw) is calculated as the total number of relapses for all the patients in the treatment group divided by the total number of days on study for all patients in the group and multiplied by 365.25 to obtain the annual rate.; Model estimates are based on a negative binomial regression model, adjusted for treatment group, age, baseline EDSS, baseline number of Gd-enhanced T1 lesions and number of relapses in previous 2 years as covariates, with log(time on study in years) as the offset variable, using the log link.	Baseline extension up to approximately 5 years
Secondary	Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set)	Free of MRI disease activity is defined as free of Gadolinium enhanced T1 lesions at any scan; free of new or enlarging T2 lesions at any scan: free of both gadolinium enhanced T1 lesions and new or enlarging T2 lesions at any scan. Number of patients analyzed = patients with at least one MRI scan during the specified time period. New lesions at a specific visit are assessed relative to the previous scheduled visit scan.; No imputation of missing scans is performed. As a result missing scans can lead to an overestimation of the proportion of patients free of a specific MRI activity.	Baseline Extension up to approximately 5 years
Secondary	Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set)	Six-month disability progression was defined relative to extension baseline EDSS score: 1.5 point increase in patients with baseline EDSS score of 0, 1.0 increase in patients with baseline EDSS score of between 0.5 to 5.0, inclusive and 0.5 increase in patients with baseline EDSS score of = 5.5. The criteria for 6-month disability progression included detection of onset of progression and confirmation of progression for a period of at least 6 months.	Baseline Extension up to approximately 5 years

External Links

•   Publication from the Journal of the American Medical Association (JAMA) - Neurology