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

NCT01185821 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CBAF312A2201E12009-014392-51
• Study Type: interventional
• Target: 185
• Locations: 12 countries
• Sites: 46

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

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

BAF312; siponimod; Multiple Sclerosis; Relapsing remitting Multiple Sclerosis; Demyelinating Autoimmune Diseases; MS; RRMS; inflammatory disease

Outcome Measures

Primary Outcomes (6)

• 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

• 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

• 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

• 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

• 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

• Number of Participants With Dermatologic Alterations - Basal Cell Carcinoma (Extension Set)

  Baseline Extension up to approximately 5 years

Secondary Outcomes (3)

• Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set)

  Baseline extension up to approximately 5 years

• Percentage of Participants Free of Magnetic Resonance Imaging (MRI) Identified Disease Activity at Any Scan During Extension Study (Extension Set)

  Baseline Extension up to approximately 5 years

• Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set)

  Baseline Extension up to approximately 5 years

Study Arms (5)

BAF312 10 mg/2 mg

EXPERIMENTAL

10 mg dose in Double Blind Phase and 2 mg in Open Label Phase

Drug: BAF312

BAF312 2 mg/2 mg

EXPERIMENTAL

2 mg dose in Double Blind Phase and 2 mg in Open Label Phase

Drug: BAF312

BAF312 1.25 mg/2 mg

EXPERIMENTAL

1.25 mg dose in Double Blind Phase and 2 mg in Open Label Phase

Drug: BAF312

BAF312 .5 mg/2 mg

EXPERIMENTAL

.5 mg dose in Double Blind Phase and 2 mg in Open Label Phase

Drug: BAF312

BAF312 .25 mg/2 mg

EXPERIMENTAL

.25 mg dose in Double Blind Phase and 2 mg in Open Label Phase

Drug: BAF312

Interventions

BAF312 DRUG

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.

Also known as: siponimod

BAF312 .25 mg/2 mg; BAF312 .5 mg/2 mg; BAF312 1.25 mg/2 mg; BAF312 10 mg/2 mg; BAF312 2 mg/2 mg

Eligibility Criteria

• Age: 18 Years - 56 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (46)

Novartis Investigative Site

Miami, Florida, 33136, United States

Location

Novartis Investigative Site

Pompano Beach, Florida, 33060, United States

Location

Novartis Investigative Site

Tallahassee, Florida, 32308, United States

Location

Novartis Investigative Site

Chicago, Illinois, 60637, United States

Location

Novartis Investigative Site

Grand Rapids, Michigan, 49525, United States

Location

Novartis Investigative Site

Akron, Ohio, 44320, United States

Location

Novartis Investigative Site

Greenville, South Carolina, 29607, United States

Location

Novartis Investigative Site

Seattle, Washington, 98122, United States

Location

Novartis Investigative Site

Ottawa, Ontario, K1H 8L6, Canada

Location

Novartis Investigative Site

Gatineau, Quebec, J9J 0A5, Canada

Location

Novartis Investigative Site

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Novartis Investigative Site

Helsinki, 00930, Finland

Location

Novartis Investigative Site

Tampere, FIN-33520, Finland

Location

Novartis Investigative Site

Dresden, 01307, Germany

Location

Novartis Investigative Site

Ibbenbueren, 49477, Germany

Location

Novartis Investigative Site

München, 81675, Germany

Location

Novartis Investigative Site

Münster, 48149, Germany

Location

Novartis Investigative Site

Budapest, 1076, Hungary

Location

Novartis Investigative Site

Budapest, 1145, Hungary

Location

Novartis Investigative Site

Debrecen, 4032, Hungary

Location

Novartis Investigative Site

Veszprém, H-8200, Hungary

Location

Novartis Investigative Site

Montichiari, BS, 25018, Italy

Location

Novartis Investigative Site

Chieti, CH, 66100, Italy

Location

Novartis Investigative Site

Roma, RM, 00133, Italy

Location

Novartis Investigative Site

Roma, RM, 00152, Italy

Location

Novartis Investigative Site

Bergen, 5021, Norway

Location

Novartis Investigative Site

Oslo, 0424, Norway

Location

Novartis Investigative Site

Lodz, 90-324, Poland

Location

Novartis Investigative Site

Lublin, 20-954, Poland

Location

Novartis Investigative Site

Warsaw, 02-957, Poland

Location

Novartis Investigative Site

Kazan', 420103, Russia

Location

Novartis Investigative Site

Moscow, 125367, Russia

Location

Novartis Investigative Site

Moscow, 127018, Russia

Location

Novartis Investigative Site

Saint Petersburg, 194044, Russia

Location

Novartis Investigative Site

Saint Petersburg, 197022, Russia

Location

Novartis Investigative Site

Seville, Andalusia, 41009, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Valencia, Valencia, 46026, Spain

Location

Novartis Investigative Site

Basel, 4031, Switzerland

Location

Novartis Investigative Site

Lugano, 6900, Switzerland

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Ankara, 06100, Turkey (Türkiye)

Location

Novartis Investigative Site

Haseki / Istanbul, 34096, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, 35340, Turkey (Türkiye)

Location

Novartis Investigative Site

Kocaeli, 41380, Turkey (Türkiye)

Location

Related Publications (1)

• 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.

  PMID: 27380540 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

siponimod

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking continued during the double blind period of extension only.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: August 19, 2010
• First Posted: August 20, 2010
• Study Start: August 30, 2010
• Primary Completion: October 10, 2016
• Study Completion: October 10, 2016
• Last Updated: March 27, 2018
• Results First Posted: December 12, 2017

Record last verified: 2018-02

Locations

TU (5); CA (3); US (8); RU (5); CH (3); FI (2); DE (4); NO (2); PL (3); ES (3); HU (4); IT (4)