Nervous System Diseases

Immune System Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Rare Diseases

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Sclerosis

Neoplasm Metastasis

Autoimmune Diseases

Demyelinating Autoimmune Diseases, CNS

Autoimmune Diseases of the Nervous System

Demyelinating Diseases

Neoplastic Processes

Chronic Disease

Disease Attributes

Chronic Graft Versus Host Disease

All Drugs and Chemicals

Siponimod

Immunosuppressive Agents

Immunologic Factors

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.

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.

0.25, 0.5, 1, and 2 mg film-coated tablets

BAF312

Placebo

Novartis Pharmaceuticals

Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis (Core Part) followed by extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability and efficacy (Extension Part).

Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Locations: central Contact Info Novartis.email@novartis.com

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). Confirmed disability 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.

Delay in time to 3 month confirmed worsening of at least 20% from baseline in the timed 25 foot walk test.

Efficacy is shown by the reduction of the increase in T1 lesion volume.

Confirmed disability is defined as 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.

Efficacy of BAF312 relative to placebo was measured by the effect on confirmed relapses rate, the time to the first relapse, and proportion of patient free from relapses.

The overall response of the effect of BAF312 compared to placebo patients on the patient reported outcome form MSWS-12.

Effect of BAF312 relative to placebo on disease activity and burden of disease as measured by Gd-T1 lesion, new/enlarged T2 lesion, and brain atrophy on brain MRI scans.

effect on confirmed disability progression in pre-defined subgroups, including patients with or without superimposed relapses, rapidly evolving patients with 1.5 point or greater change in EDSS score in 2 years prior to enrollment into the study. Patients with score of 4 or more in MSSS and those who don't meet this criteria.

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 2 mg BAF312 daily for a variable duration.

Siponimod (BAF312)

Matching placebo to BAF312 was administered orally during the Core Part of the trial.

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Study Director

The Full analysis set (FAS), which comprised all randomized patients with assigned treatments who took at least one dose of study medication, was considered for the analysis. Only participants from the FAS with non-missing covariates were analyzed for this outcome.

Percentage of Participants With 3-month Confirmed Disibility Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)

Efficacy of BAF312 Relative to Placebo in Confirmed Worsening of 25 Foot Walk Test

Efficacy of BAF312 Relative to Placebo in Reducing the Increase in T2 Lesion Volume

The Delay in Time to Confirmed Disability Progression as Measured by EDSS.

Efficacy of BAF Relative to Placebo in Annualized Relapses Rate and Time to the First Relapse

Overall Response Rate on the MSWS-12.

Effect on Inflammatory Disease Activity and Burden of Disease as Measured by MRI

Effect on 3-month Confirmed Disability Progression as Defined by EDSS in Predefined Sub-groups

Overall Study

Infections

Respiratory Tract (Lung and Bronchial) Diseases

COVID-19

Anti-Infective Agents

Antineoplastic Agents

Dermatologic Agents

Vaccines

Interferons

Dimethyl Fumarate

Continuous treatment with siponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) during SARS-CoV-2 mRNA vaccination

Siponimod (oral, daily, dose depending on CYP2C9 genotype: 2mg or 1 mg) with treatment interruption (for approx. 2-3 months) for the purpose of a SARS-CoV-2 mRNA vaccination

Baseline DMTs or no treatment during SARS-CoV-2 mRNA vaccination

taken orally once per day (dose depends on CYP2C9 genotype)

DMTs: Dimethylfumarate, glatirameracetate, interferon, teriflunomode according to respective SmPC

Baseline disease modifying therapies (DMTs)

Administerd according to the respective EU SmPC at the discretion of the treating physician independent of AMA-VACC. If suggested by local regulations and performed as part of clinical routine any type of booster/refresher vaccination (e.g. mRNA, vector, peptide) was allowed in this study.

BNT162

Administerd according to the respective EU SmPC at the discretion of the treating physician independent of AMA-VACC. If suggested by local regulations and performed as part of clinical routine any type of booster/refresher vaccination (e.g. mRNA, vector, peptide) was allowed in this study

mRNA-1273

The purpose of this study was to understand whether participants could mount an immune response to SARS-CoV-2 modRNA vaccines administered either during continuous siponimod treatment or during a treatment break versus while on treatment with first-line DMTS or no current MS treatment..

This was a three cohort, multicenter, open-label, study of 60 planned (optionally up to 90) multiple sclerosis (MS) patients who were on treatment with siponimod or a first-line disease modifying therapy (DMT) or without MS treatment planning to undergo a SARS-CoV-2 modRNA vaccination as part of clinical routine.

* The first cohort enrolled participants who did not interrupt their siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination.
* The second cohort enrolled participants who interrupted their siponimod therapy for the purpose of a SARS-CoV-2 modRNA vaccination for approximately 2-3 months
* The third cohort enrollled participants who received modRNA vaccination while on treatment with the following first-line DMTs (dimethylfumarate, glatirameracetate, interferons, teriflunomide) or no current treatment in clinical routine.

The study consists of a screening period, vaccination period and investigational period. During the screening period of up to one month eligibility and SARS-CoV-2 antibodies at baseline were assessed. The 3-4 week vaccination period started with first dose of modRNA vaccine on Day 1 and ended with second dose of modRNA vaccine 3-4 weeks after first dose depending on EU SmPC.

The investigational period lasted 12 months, during which blood samples for primary and secondary endpoint analyses were drawn at 1 week (Visit 1), 1 Month (Visit 2) and 6 months (Visit 3) after completion of vaccination (i.e. second dose of vaccine). 12 months after completion of vaccination a COVID-19 follow-up call was scheduled.

As patients were treated according to clinical routine, the start of treatment was defined as the date the informed consent was signed.

Booster vaccinations were allowed as per local regulations, physician's discretion and as part of clinical routine. This booster may have been any type of SARS-CoV2 vaccine and introduction of a treatment break for the purpose of booster vaccination was at the discretion of the treating physician or patient for all three cohorts. In case of booster vaccinations an additional blood sample was collected 1 month after the booster vaccination (booster Visit).

The planned study duration for each participant was 56-64 weeks, depending on the length of the screening period.

The study investigated the development of functional anti-SARS-CoV-2 antibodies and T-cell titers for six months after the participants' vaccination.

Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC)

An Open-label Multicenter Study to Assess Response to SARS-CoV-2 modRNA Vaccines in Participants With Secondary Progressive Multiple Sclerosis Treated With Mayzent (Siponimod)

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on https://www.clinicalstudydatarequest.com/.

Participants who had detectable SARS-CoV-2 serum functional antibodies one week after second dose of vaccine.

Measurement of antibody-mediated blockage (i.e. presence of functional SARS-CoV-2 antibodies) was performed to quantify functional SARS-CoV-2 neutralizing antibodies and was calculated as % inhibition to the in-assay control.

The release of IFNg or IL-2 after stimulation with a SARS-CoV-2/PAN corona peptide-mix measured by enzyme-linked immunosorbent spot (ELIspot) assay from peripheral blood mononuclear cells indicates the presence of SARS-CoV-2 reactive T-cells, i.e. a T-cell response.

The signing of the Informed Consent was considered the start of treatment for this trial because participants entered the trial on treatment as part of their clinical routine.

Siponimod Continuous

Siponimod Interrupted

Baseline disease modifying treatments (DMTs) or no multiple sclerosis treatment during SARS-CoV-2 mRNA vaccination

DMT or No MS Treatment

Siponimod - Continuous

Siponimod- Interrupted

DMT or no MS Treatment

Caucasian

African

Other

Missing

Race/Ethnicity, Customized

SPMS Secondary progressive multiple sclerosis

RRMS Relapsing remitting multiple sclerosis

Active SPMS (with acute exacerbation or progression)

MS Multiple sclerosis, not specified

Active RRMS (with acute exacerbation or progression)

The diagnosis of type of multiple sclerosis at baseline.

Multiple sclerosis diagnosis

Efficacy analysis set (EAS) - all participants who had a valid primary endpoint (i. e. determination of functional antibodies to SARS-CoV-2 at Week 1 after second dose of vaccine)

Percentage of Participants Achieving Seroconversion One Week After Receiving Second Vaccine (EAS)

Screening n=17,4,20

Visit 1/Week 1 n=17,4,20

Visit 2/Month 1 n=16,4,20

Visit 3/Month 6 n=16,4,20

1 Month after booster n=16,4,18

Safety analysis set (received any study drug) and efficacy analysis set (participants with a valid primary endpoint)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)	NCT01665144	Secondary Progr...	BAF312 Placebo	18 Years - 60 Years	Novartis
Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC)	NCT04792567	Secondary Progr...	BAF312 Baseline diseas... BNT162 mRNA-1273	18 Years - 100 Years	Novartis
Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)	NCT01665144	Secondary Progr...	BAF312 Placebo	18 Years - 60 Years	Novartis
Exploring the Immune Response to SARS-CoV-2 modRNA Vaccines in Patients With Secondary Progressive Multiple Sclerosis (AMA-VACC)	NCT04792567	Secondary Progr...	BAF312 Baseline diseas... BNT162 mRNA-1273	18 Years - 100 Years	Novartis

Spots Global Cancer Trial Database for baf312

Every month we try and update this database with for baf312 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for baf312

Every month we try and update this database with for baf312 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for baf312 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.