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

CompletedPhase 2Relapsing MSNCT01185821 2009-014392-51

What it found

Main goal was not benefit

The main measure was safety, drug levels or similar, not whether the treatment works.

“The incidence of adverse events was similar across treatment groups (10 mg: 87.9%; 2 mg: 89.7%; 1.25 mg: 88.4%; 0.5 mg: 96.6%; and 0.25 mg: 84.0%).”

Read by software from the paper's abstract

up to 24 months

Total participants: 252

Read by software from the paper's abstract

What was tested

Treatment tested

Siponimod
Sphingosine 1-phosphate receptor Edg-1 agonist

Results by group

Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study.

Baseline up to approximately 5 years

Group	Value	Number analysed
BAF312 10 mg/2 mg	4 events	33
BAF312 2 mg/2 mg	7 events	29
BAF312 1.25 mg/2 mg	6 events	43
BAF312 .5 mg/2 mg	6 events	29
BAF312 .25 mg/2 mg	8 events	50
BAF312 10 mg/2 mg	30 events	33
BAF312 2 mg/2 mg	26 events	29
BAF312 1.25 mg/2 mg	42 events	43
BAF312 .5 mg/2 mg	29 events	29
BAF312 .25 mg/2 mg	42 events	50

Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout)

Baseline Extension up to day 10

Group	Value	Number analysed
BAF312 10 mg/2 mg	5 participants	33
BAF312 2 mg/2 mg	2 participants	29
BAF312 1.25 mg/2 mg	5 participants	39
BAF312 .5 mg/2 mg	2 participants	29
BAF312 .25 mg/2 mg	4 participants	33
BAF312 10 mg/2 mg	3 participants	33
BAF312 2 mg/2 mg	8 participants	29
BAF312 1.25 mg/2 mg	1 participants	39
BAF312 .5 mg/2 mg	3 participants	29
BAF312 .25 mg/2 mg	0 participants	33
BAF312 10 mg/2 mg	1 participants	33
BAF312 2 mg/2 mg	0 participants	29
BAF312 1.25 mg/2 mg	0 participants	39
BAF312 .5 mg/2 mg	0 participants	29
BAF312 .25 mg/2 mg	0 participants	33
BAF312 10 mg/2 mg	0 participants	33
BAF312 2 mg/2 mg	1 participants	29
BAF312 1.25 mg/2 mg	1 participants	39
BAF312 .5 mg/2 mg	1 participants	29
BAF312 .25 mg/2 mg	1 participants	33
BAF312 10 mg/2 mg	0 participants	33
BAF312 2 mg/2 mg	0 participants	29
BAF312 1.25 mg/2 mg	0 participants	39
BAF312 .5 mg/2 mg	1 participants	29
BAF312 .25 mg/2 mg	0 participants	33

Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout)

Baseline Extension up to day 10

Group	Value	Interval	Number analysed
BAF312 .25 mg/2 mg	4 participants		4

Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set)

Baseline Extension up to approximately 5 years

Group	Value	Number analysed
BAF312 10 mg/2 mg	1 participants	33
BAF312 2 mg/2 mg	3 participants	29
BAF312 1.25 mg/2 mg	2 participants	43
BAF312 .5 mg/2 mg	1 participants	29
BAF312 .25 mg/2 mg	1 participants	50
BAF312 10 mg/2 mg	8 participants	33
BAF312 2 mg/2 mg	10 participants	29
BAF312 1.25 mg/2 mg	4 participants	43
BAF312 .5 mg/2 mg	6 participants	29
BAF312 .25 mg/2 mg	10 participants	50
BAF312 10 mg/2 mg	1 participants	33
BAF312 2 mg/2 mg	1 participants	29
BAF312 1.25 mg/2 mg	1 participants	43
BAF312 .5 mg/2 mg	3 participants	29
BAF312 .25 mg/2 mg	3 participants	50
BAF312 10 mg/2 mg	9 participants	33
BAF312 2 mg/2 mg	8 participants	29
BAF312 1.25 mg/2 mg	12 participants	43
BAF312 .5 mg/2 mg	13 participants	29
BAF312 .25 mg/2 mg	18 participants	50
BAF312 10 mg/2 mg	1 participants	33
BAF312 2 mg/2 mg	0 participants	29
BAF312 1.25 mg/2 mg	1 participants	43
BAF312 .5 mg/2 mg	0 participants	29
BAF312 .25 mg/2 mg	1 participants	50
BAF312 10 mg/2 mg	14 participants	33
BAF312 2 mg/2 mg	8 participants	29
BAF312 1.25 mg/2 mg	10 participants	43
BAF312 .5 mg/2 mg	10 participants	29
BAF312 .25 mg/2 mg	10 participants	50
BAF312 10 mg/2 mg	4 participants	33
BAF312 2 mg/2 mg	7 participants	29
BAF312 1.25 mg/2 mg	4 participants	43
BAF312 .5 mg/2 mg	4 participants	29
BAF312 .25 mg/2 mg	4 participants	50
BAF312 10 mg/2 mg	9 participants	33
BAF312 2 mg/2 mg	13 participants	29
BAF312 1.25 mg/2 mg	13 participants	43
BAF312 .5 mg/2 mg	11 participants	29
BAF312 .25 mg/2 mg	17 participants	50

Number of Participants With Viral Infections of Interest Greater or Equal to 5% in Any Dose Group (Extension Set)

Baseline Extension up to approximately 5 years

Group	Value	Number analysed
BAF312 10 mg/2 mg	5 participants	33
BAF312 2 mg/2 mg	0 participants	29
BAF312 1.25 mg/2 mg	4 participants	43
BAF312 .5 mg/2 mg	2 participants	29
BAF312 .25 mg/2 mg	4 participants	50
BAF312 10 mg/2 mg	5 participants	33
BAF312 2 mg/2 mg	0 participants	29
BAF312 1.25 mg/2 mg	3 participants	43
BAF312 .5 mg/2 mg	2 participants	29
BAF312 .25 mg/2 mg	0 participants	50
BAF312 10 mg/2 mg	3 participants	33
BAF312 2 mg/2 mg	4 participants	29
BAF312 1.25 mg/2 mg	3 participants	43
BAF312 .5 mg/2 mg	6 participants	29
BAF312 .25 mg/2 mg	6 participants	50

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

Baseline Extension up to approximately 5 years

Group	Value	Number analysed
BAF312 10 mg/2 mg	1 participants	33
BAF312 2 mg/2 mg	0 participants	29
BAF312 1.25 mg/2 mg	1 participants	43
BAF312 .5 mg/2 mg	0 participants	29
BAF312 .25 mg/2 mg	1 participants	50

Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.

Safety

Group	Participants at risk	Serious adverse events
BAF312 10/2 mg	33	4 (12.1%)
BAF312 2/2 mg	29	7 (24.1%)
BAF312 1.25/2 mg	43	6 (14.0%)
BAF312 0.5/2 mg	29	6 (20.7%)
BAF312 0.25/2 mg	50	8 (16.0%)
All Patients	184	31 (16.8%)

As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.

What it measured

Main measures

Total Number of Adverse Events During Evaluation of Long Term Safety and Tolerability of BAF312A in Extension Study.
Baseline up to approximately 5 years
Safety
Number of Participants With Cardiac Conduction Abnormalities During the Titration Phase of the Study (Without Washout)
Baseline Extension up to day 10
Number of Participants With Cardiac Conduction-IVCD Abnormality During the Titration Phase of the Study (With Washout)
Baseline Extension up to day 10
Number of Participants With Changes in Blood Pressure for Overall Extension Study. (Extension Analysis Set)
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)
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
El objetivo principal de este estudio es evaluar la seguridad a largo plazo. Los parámetros de seguridad de interés específico son la presión arterial, las infecciones víricas, el edema macular y las alteraciones dermatológicas.

Other measures (3)

Number of Relapses in One Year - Annualized Relapse Rates for Overall Extension Study (ARR) (Extension Set)
Baseline extension up to approximately 5 years
Disability progressionRelapsesMRI lesions
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
MRI lesions
Percentage of Participants Free of Confirmed Disability Progression in Extension Study (Extension Set)
Baseline Extension up to approximately 5 years
Disability progression

Who could take part

Relapsing MS · 18 to 56

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

As registered. Criteria can change, so ask the trial team or your neurologist.

About this trial

In the sponsor's words

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

Papers

Results
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
The incidence of adverse events was similar across treatment groups (10 mg: 87.9%; 2 mg: 89.7%; 1.25 mg: 88.4%; 0.5 mg: 96.6%; and 0.25 mg: 84.0%).
Read by software from the paper's abstract

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History

Started
Aug 2010
Main results due
Oct 2016
Finished
Oct 2016
Results posted
Dec 2017

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