Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
BAF312 · 6 trials · 7 indications
The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel \& Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). 3-month confirmed disability progression is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5 sustained for at least 3 months.
Following the initial diagnostic CT, repeat CT images were obtained between 24-48 h after the diagnostic scan, and on Day 7 and Day 14 to capture the trajectory of PHE increase and plateau after ICH. Only non-contrast study CT scans were obtained on Day 7 and Day 14. The non-contrast scan acquired on each patient at first follow-up (i.e. 24-48 h after the diagnostic scan) served as the baseline for our analysis. All CT scans were uploaded through a secure server, and edema and hematoma volumes were measured in a semi-automated manner by one Central Reader.
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.
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
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
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.
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
Combined unique active lesions (CUAL) were defined as new gadolinium \[Gd\]-enhanced lesions on T1-weighted MRI scans or new or enlarging lesions on T2-weighted MRI scans, without double-counting of lesions. ED50 is the dose that gives half of the asymptotic maximum change over placebo. ED90 is the dose that gives 90% of the asymptotic maximum change over placebo.
The pharmacokineticsof BAF312 will be studied in plasma up to 312 (+/-24) hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, and 312 (+/-24) hours post dose. Selected metabolites will also be quantified using the same samples as described above. Free plasma circulating fraction of BAF312 will also be investigated to assess whether protein binding is affected by renal impairment. For this purpose a separate blood sample will be taken at the following time point: 4 hours post-dose.
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose.
The pharmacokinetics of BAF312 were studied in plasma up to 504 hours post-dose at the following time points: pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, 144, 216, 312, 408 and 504 hours post dose
| Arm | Type | Description |
|---|---|---|
| Siponimod (BAF312) | EXPERIMENTAL | Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312. |
| Placebo | PLACEBO_COMPARATOR | Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312. |
| BAF312 | EXPERIMENTAL | Days 1 - 7, IV up titration; days 8 - 14, 10 mg (5 x 2 mg tablets) taken daily orally |
| BAF312 10 mg/2 mg | EXPERIMENTAL | 10 mg dose in Double Blind Phase and 2 mg in Open Label Phase |
| BAF312 2 mg/2 mg | EXPERIMENTAL | 2 mg dose in Double Blind Phase and 2 mg in Open Label Phase |
| BAF312 1.25 mg/2 mg | EXPERIMENTAL | 1.25 mg dose in Double Blind Phase and 2 mg in Open Label Phase |
| BAF312 .5 mg/2 mg | EXPERIMENTAL | .5 mg dose in Double Blind Phase and 2 mg in Open Label Phase |
| BAF312 .25 mg/2 mg | EXPERIMENTAL | .25 mg dose in Double Blind Phase and 2 mg in Open Label Phase |
| BAF312 10mg (period 1) | EXPERIMENTAL | - |
| BAF312 2 mg (period 1) | EXPERIMENTAL | - |
| BAF312 0.5 mg (period 1) | EXPERIMENTAL | - |
| BAF312 dose between 0.1 to 8 mg period 2 | EXPERIMENTAL | - |
| BAF312 dose between 0.1 - 8 mg period 2 | EXPERIMENTAL | - |
| Placebo (period 1, 2) | PLACEBO_COMPARATOR | - |
| severe renal impairmnt | EXPERIMENTAL | - |
| moderate renal impairment | EXPERIMENTAL | - |
| mild renal impairment | EXPERIMENTAL | - |
| healthy subjects | EXPERIMENTAL | - |
| Mild hepatically impaired | EXPERIMENTAL | Treatment with a single oral dose of 0.25 mg BAF312 |
| Moderate hepatically impaired | EXPERIMENTAL | Treatment with a single oral dose of 0.25 mg BAF312 |
| Severe hepatically impaired | EXPERIMENTAL | Treatment with a single oral dose of 0.25 mg BAF312 |
| Matched healthy subjects | EXPERIMENTAL | Treatment with a single oral dose of 0.25 mg BAF312 |
| Name | Type | Description |
|---|---|---|
| BAF312 | DRUG | 0.25, 0.5, 1, and 2 mg film-coated tablets |
| Placebo | DRUG | Film-coated tablets |
| BAF312 solution | DRUG | Solution for intravenous (IV) infusion - 4.5mg/4.5mL |
| Matching Placebo for BAF312 solution | DRUG | Solution for intravenous (IV) infusion - 0mg/4.5mL matching placebo |
| BAF312 tablet | DRUG | 2 mg film-coated tablet |
| Matching Placebo for BAF312 tablet | DRUG | 0 mg film-coated tablet matching placebo |
Inclusion Criteria: * Prior history of relapsing remitting MS * SPMS defined as progressive increase of disability over at least 6 months * EDSS score of 3.0 to 6.5 * No relapse of corticosteroid treatment within 3 months Exclusion Criteria: * Women of child bearing potential must use reliable fo...
BAF 312 is an investigational small molecule being studied for multiple conditions, including relapsing-remitting multiple sclerosis, secondary progressive multiple sclerosis, hepatic impairment, renal impairment, hemorrhagic stroke, and in healthy volunteers. It is being developed by Novartis AG.
BAF 312 is a small molecule that acts as a sphingosine 1-phosphate receptor modulator. It is being studied for its potential effects on immune cell trafficking in conditions like multiple sclerosis and hemorrhagic stroke.
BAF 312 is being developed by Novartis AG, a global healthcare company traded on the New York Stock Exchange under the ticker NVS. Novartis is conducting clinical trials to evaluate the drug's safety and efficacy across several indications.
BAF 312 is in clinical development. It has completed Phase 1, Phase 2, and Phase 3 trials. The most advanced completed trial was a Phase 3 study in secondary progressive multiple sclerosis, while earlier-phase studies covered hepatic impairment and relapsing-remitting multiple sclerosis.
BAF 312 has been studied in several completed trials. NCT01185821 was a Phase 2 study in relapsing-remitting multiple sclerosis. NCT01565902 was a Phase 1 pharmacokinetic study in hepatic impairment. NCT01665144 was a Phase 3 trial in secondary progressive multiple sclerosis, and NCT03338998 was a Phase 2 study in intracerebral hemorrhage.
Yes, BAF 312 is also known as siponimod. In clinical trials, it has been referred to by both names, including in the EXPAND study for secondary progressive multiple sclerosis, which evaluated siponimod in over 1,600 patients.