Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as BAF312 solution, siponimod
BAF312 · 7 trials · 10 indications
An Adverse Event (AE) is any untoward medical occurrence in a participant that does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporarily associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs are defined as the AEs started after the first dose of siponimod to 30 days after the date of the last actual administration, or events present prior to start of treatment but which increased in severity. TEAEs suspected to be related to study drug are reported.
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 | EXPERIMENTAL | Participants will receive titrated doses of siponimod tablets, orally, once daily of 0.25 mg on Day 2, 0.5 mg on Day 3, 0.75 mg on Day 4, 1.25 mg on Day 5, and maintenance dose of siponimod 2.0 mg tablets, orally, once daily from Day 6 up to 6 months. As of protocol amendment 3, participants entering the trial converting from fingolimod will start directly with 2 mg dose of siponimod. |
| 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 |
|---|---|---|
| Siponimod | DRUG | Siponimod 2mg tablets taken once daily |
| 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 |
Key Inclusion Criteria: 1. Signed informed consent. 2. Male or female aged 18 to 65 years (inclusive). 3. Patients with advancing RMS as defined by the principal investigator. 4. Prior history of relapsing MS (RMS), with or without progressive features, according to the 2010 Revised McDonald or Lub...
BAF312 is an investigational small molecule developed by Novartis AG for neurological conditions. It has been studied in relapsing remitting multiple sclerosis, secondary progressive multiple sclerosis, hemorrhagic stroke, hepatic impairment, and renal impairment. The program includes completed Phase 1, Phase 2, and Phase 3 clinical trials.
BAF312 has been studied for several indications: secondary progressive multiple sclerosis, relapsing remitting multiple sclerosis, hemorrhagic stroke including intracerebral hemorrhage, hepatic impairment, and renal impairment. These represent the conditions evaluated in its clinical development program rather than approved uses.
Novartis AG, which trades under the ticker NVS, is the developer of BAF312. The company has sponsored the clinical trials evaluating the compound across multiple sclerosis, hemorrhagic stroke, and organ impairment studies.
BAF312 has completed Phase 1, Phase 2, and Phase 3 clinical trials. The program includes a completed Phase 3 study in secondary progressive multiple sclerosis, a completed Phase 2 study in intracerebral hemorrhage, and completed Phase 1 pharmacokinetic studies in renal and hepatic impairment.
Completed trials include NCT01665144, the Phase 3 EXPAND study in secondary progressive multiple sclerosis with 1,651 participants, NCT03338998, a Phase 2 study in intracerebral hemorrhage, NCT01904214, a Phase 1 renal impairment study, and NCT01565902, a Phase 1 hepatic impairment study.
Yes, BAF312, BAF 312, and BAF312 solution are alternative names for the same compound. BAF312 is the primary designation used in trial records, while BAF 312 and BAF312 solution refer to the same investigational small molecule developed by Novartis AG.