Nervous System Diseases

Immune System Diseases

All Conditions

Symptoms and General Pathology

Neoplasms

Rare Diseases

Multiple Sclerosis

Multiple Sclerosis, Chronic Progressive

Sclerosis

Neoplasm Metastasis

Disease Progression

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

Patients administered Siponimod as per Swiss label

Prospective observational cohort study. There is no treatment allocation. Patients administered siponimod as by swiss label, that have started before inclusion of the patient into the study will be enrolled.

Novartis Pharmaceiticals

This study is a national, prospective, multicenter, non-interventional (observational) study with the aim to describe the impact of Siponimod treatment in a real-world SPMS population in Switzerland who are treated with Siponimod as per Swiss label.

Primary data will be collected during an observational period of three years of Siponimod treatment. Additionally, medical history of participants will be collected including EDSS, MRI outcomes, relapses and previous medication to allow the estimation of Siponimod treatment effects on an individual basis. It is planned to include an optional blood draw for a later biomarker analysis.

Swiss Study of the Impact of Mayzent on SPMS Patients in a Long-term Non-interventional Study

Swiss Study of the Impact of Mayzent (Siponimod) on Secondary Progressive Multiple Sclerosis Patients in a Long-term Non-interventional Study

The EDSS score is a widely used tool for determining the degree of disability in MS at any point in time. The EDSS value is generated based on overall impression and individual scores of the following functional systems: cognition, mood, fatigue, vision, brain stem, upper extremities, lower extremities, bladder and bowel function, sexuality. This results in a scale from 0 (healthy) to 10 (death from MS)

Disability progression based on the EDSS score is defined as a 1 point increase from baseline in patients with a baseline score of ≤ 5, or a 0.5 point increase in patients with a baseline score of ≥5.5. As part of a secondary endpoint to this study, the deterioration of the EDSS of ≥1 point (baseline EDSS ≤ 5) or 0.5 points (baseline EDSS ≥5.5) must be confirmed after 6 months. This is called 6-month confirmed progression (6M-CDPEDSS). EDSS values to confirm progression must not be determined during an attack. The maximum duration of an attack is limited to 90 days

The SDMT is a sensitive and specific test for examining attention, concentration and information processing speed, which are typically impaired in cognitively impaired MS patients.

The patients receive an SDMT test sheet. At the beginning of this sheet there are 9 numbers paired with 9 associated individual symbols. Below that are further lines with symbols and empty boxes. The patients must now verbally assign the correct numbers to the symbols as quickly as possible. Exercise examples are given at the beginning of the test which are not taken into account when evaluating the test. The number of correctly assigned items within 90 seconds results into the test score. The total duration of the test is about 5 minutes.

SDMT: ≥4.0-point confirmed worsening from baseline score sustained for at least 6 months respectively

The T25-FW is an objective and quantitative test of the lower extremities (Motl et al., 2017). This stops the time in seconds that a patient needs to walk 25 feet (7.62 m). The patient should walk as quickly and safely as possible. This test is carried out twice in succession and the mean value of the time required is documented in seconds. An improvement or deterioration of 20% is seen as a clinical meaningful change (Motl et al., 2017).

The EQ-5D patient questionnaire is a generic multidimensional measuring instrument for describing health-related quality of life (EuroQol, 1999). The five domains mobility, ability to take care of oneself, everyday activities, pain / discomfort and anxiety / depression are considered. For the individual dimensions, the most appropriate answer from three given options is selected (1 = no problem, 2 = moderate problem, 3 = major problem). In addition, the patient marks the current state of health on a scale from 0 (worst-conceivable state of health) to 100 (best-conceivable state of health).

The FSMC is a patient questionnaire to clarify cognitive and motor fatigue, a typical symptom of MS (Penner et al., 2009). With the help of the FSMC, a cognitive, a motor, and a total score are determined. Increased scores indicate higher impairment caused by fatigue.

A 5-point scale (ranging from 'does not apply at all' to 'applies completely') produces a score between 1 and 5 for each scored question.

BDI is a patient questionnaire for measuring the severity of depression (Beck, 1972). Depression is a common symptom in MS and can cause fatigue. With the BDI test we assess the frequency of depression and its correlation to fatigue. This results in a scale from 0 to 63. The level of depression is evaluated according to the table below:

* 0-13: no or minimal symptoms
* 14-19: mild symptoms
* 20-28: moderate symptoms
* 29-63: severe depressive symptoms

ESS is a patient questionnaire to measure daytime sleepiness (Ibanez et al, 2017). Results of the ESS will allow to correlate whether observed fatigue might be attributed to daytime sleepiness. The level of sleepiness is evaluated according to the table below:

0-5 Lower Normal Daytime Sleepiness 6-10 Higher Normal Daytime Sleepiness 11-12 Mild Excessive Daytime Sleepiness 13-15 Moderate Excessive Daytime Sleepiness 16-24 Severe Excessive Daytime Sleepiness

Novartis Pharmaceuticals

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)

BAF312

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

Total

Age, Continuous

Sex: Female, Male

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

Study Director

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)

SARS-CoV-2 Functional Antibodies (% Inhibition) by Visits (SAF/EAS)

Screening reactive n=17,4,20

Screening not reactive n=17,4,20

Screening missing value n=17,4,20

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

Visit 1/Week 1 not reactive n=17,4,20

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

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

Visit 2/Month 1 not reactive n=16,4,20

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

Visit 3/Month 6 reactive n=17,4,20

Visit 3/Month 6 not reactive n=17,4,20

Visit 3/Month 6 missing value n=17,4,20

Visit 1 Month after booster reactive n=16,4,18

Visit 1 Month after booster not reactive n=16,4,18

Visit 1 Month after booster missing value n=16,4,18

Number of Patients Reactive to INFg or IL-2 SARS-CoV-2 by Visit SAF/EAS

Overall Study

Patients administered Mayzent by prescription

There is no treatment allocation. Patients administered Mayzent by prescription that have started before inclusion of the patient into the study will be enrolled.

Mayzent

This study is a single cohort, central registration system, all-case, open-label, multicenter observational study in patients using Mayzent for the indication of secondary progressive multiple sclerosis.

This is a non-interventional study, and as such there is no binding treatment strategy, diagnosis/treatment procedures or visit schedule. The investigator should administer Mayzent as labelled. Routine medical practice will apply to visit frequency and evaluation variables, and only these data will be collected by the sponsor as part of the study procedures. The investigator should record data in the applicable CRFs at every visit if possible.

Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients

Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients (Prevention of Relapses and Delay of Progression of Physical Disability in Secondary Progressive Multiple Sclerosis)

A SAE is defined as an AE whose description suggests that it is serious or whose outcome is fatal.

An adverse reaction is defined as an adverse event that is suspected by the investigator to be causally related to Mayzent or whose causality is not recorded

Secondary Progressive Multiple Sclerosis (SPMS) symptom changes will be assessed an rated as "very much improved", "improved", "unchanged", "worsening" or "not assessable" in comparison with the symptoms at the start of Mayzent administration

EDSS assesses disability. An overall score ranging from 0 (normal) to 10 (death due to MS) will be calculated.

Disability progression is defined as an increase of 1.5 points or more in patients with an EDSS score of 0 at baseline, an increase of 1 point or more in patients with an EDSS score of 0.5 to 5 at baseline and an increase of 0.5 points or more in patients with an EDSS score of 5.5 or more at baseline.

Prospective observational cohort study. There is no treatment allocation. Patients will be invited to participate in the study after the independent decision by physician and patient to start siponimod treatment as routine clinical care.

siponimod

This is an observational, multicenter, single-arm, prospective study conducted in Italy

Primary data will be collected over a period of three years. Medical history of participants will be collected including EDSS, MRI outcomes, relapses and previous medication to allow the estimation of the effects of siponimod treatment on an individual basis.

Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy

Impact of Mayzent (Siponimod) on Active Secondary Progressive Multiple Sclerosis Patients in a Long-term Non-interventional Study in Italy

Confirmed disability progression (CDP) is defined as a ≥1.0-point worsening of Expanded Disability Status Scale (EDSS) score from ≤5.0 baseline or a 0.5-point worsening from \>5.0 baseline for at least 6 months OR a ≥4.0-point confirmed cognitive worsening (CCW) from baseline of Symbol Digit Modalities Test (SDMT) for at least 6 months.

ARR is the number of relapses during the period / person-years of subject Person-years for subject = period (in days) / 365.25

Number of new/newly enlarging T2-hyperintense lesions and number of new 1 gadolinium-enhancing (Gd+) lesions is collected

Expanded Disability Status Scale (EDSS) score is composed of the overall impression and individual scores of the following functional systems: cognition, mood, fatigue, vision, brain stem, upper extremities, lower extremities, bladder-intestinal function, sexuality. Scores are on a scale of 0 (healthy) to 10 (death from MS) with 0.5 unit increments

EDSS trend is measured by differentiating patients who stabilize from those who experience an increase of EDSS score (increment of ≥1 or ≥0.5 point if baseline EDSS was ≤5.0 or ˃5.0, respectively). Moreover, patients with progression will be categorized as patients with continuous disability accrual (CDA) or one-step worsening (OneS-wors), defined as:

* OneS-wors: the occurrence of one single episode of confirmed EDSS deterioration.
* CDA: occurrence of at least two episodes of OneS-wors associated with continuous disability progression between at least two time points.

NEDA-3 is defined as no Confirmed disability progression (CDP), no confirmed relapse and absence of T1 gadolinium-enhancing (Gd+) lesions.

The UKNDS is a questionnaire for recording impairments in MS from the patient's perspective and considers 12 functional systems: perception and thinking, mood, vision, speech and communication, swallowing, arm and hand function, walking ability, bladder function, bowel function, fatigue, sexuality, pain, cramps and others. Answering the questions results in a score of 0 (no disability) to 60 (maximum disability). This questionnaire will be completed by the patients during site visits.

The FSMC is a patient questionnaire for the clarification of cognitive and motor fatigue, a typical symptom of MS (Penner et al., 2009), and considers a cognitive, motor and total score. Score ranges from 200 to 100, the greater the score the greater the impairment caused by fatigue.

The HADS has seven items each for depression and anxiety subscales. Scoring for each item ranges from zero to three, with three denoting highest anxiety or depression level. A total subscale score of \>8 points out of a possible 21 denotes considerable symptoms of anxiety or depression.

Calculations of scores: each of the 14 items is rated on a 4-point scale ('Yes, definitely', 'Yes, sometimes', 'No, not much' and 'No, not at all'). All items except 7 and 10 are scored as 'Yes, definitely' = 3 to 'No, not at all' = 0. Items 7 and 10 are scored as 'Yes, definitely' = 0 to 'No, not at all' = 3. The HADS consists of two sub-scores: the HAD-A for anxiety and HAD-D for depression; each sub-score ranges from 0 to 21 points; scores ≥11 indicate the presence of anxious or depressive disorders; scores between 8-10 points are borderline abnormal, and scores of ≤7 indicate that the disorder is not present.

The SDMT is a sensitive and specific test to investigate attention, concentration and information processing speed, which are typically impaired in cognitively impaired MS patients.

Nine numbers are shown paired with 9 corresponding individual symbols. Below this are further lines with symbols and empty boxes. The patients must assign the correct numbers to the symbols as quickly as possible. The number of correctly assigned numbers within 90 seconds gives the test score. The total duration of the test is about 5 minutes and scores range between 0 and 110 where higher scores indicate better result.

A deterioration of the SDMT score by ≥4 points is considered clinically relevant

The CGI scale represents a short, independent assessment by the treating physician of the overall condition of the patient.

It incorporates patient history, psychosocial circumstances, symptoms, behavior and the influence of symptoms on the patient's functional ability. The CGI consists of three different global measures and all three will be evaluated: Severity of illness (CGI-S) ranges from 0 to 7, Global Improvement (CGI-I) ranges from 0 to 7 and Efficacy index (CGI-E) ranges from 0 to 16. A higher score means a severe impact on the disease.

Number of relapse, number of relapse that affects the daily activities, number of relapse that required an hospitalization and number of treated relapse to be collected

Number of patients with presence of symptoms to be collected

The T25-FW is an objective and quantitative test of the lower extremities. The time in seconds it takes a patient to walk a distance of 25 feet (7.62 m) is measured. The patient should walk as quickly and safely as possible. This test is performed twice in a row and the mean value of the time required is documented in seconds. An improvement or deterioration of 20% is considered a significant change

This test examines manual dexterity. Patients must individually remove nine pegs from a flat dish with one hand and insert them into corresponding holes in a test board. The pegs are then placed back into the dish with the same hand. Two rounds are performed per hand and the average value of the time required is documented in seconds

The EQ-5D is a generic multidimensional measurement tool for describing health-related quality of life (EuroQol, 1999). The five domains of mobility, self-care ability, daily activities, pain/discomfort and anxiety/depression are considered. For each of the dimensions, the most appropriate answer from three given possibilities is selected (1=no problem, 2=moderate problem, 3=large problem). In addition, the patient marks the current state of health on a scale from 0 (worst conceivable state of health) to 100 (best conceivable state of health).

The TSQM-9 is a questionnaire to assess patient satisfaction with siponimod treatment. The TSQM-9 is a sound and valid measure of the major dimensions of patients' satisfaction with medication and also a good predictor of adherence across different types of medication and patient population.

Effectiveness, side effects, simplicity and overall satisfaction are all rated between 0 and 100. Higher values mean a worse condition. Responses to items are summed and transformed so that higher scores indicate greater satisfaction. Specifically, TSQM-9 scale scores are computed by adding the items loading on each domain. The lowest possible score is subtracted from the composite score and divided by the greatest possible score range. This provides a transformed score between 0 and 1 that is then multiplied by 100. If more than one item is missing from a subscale of the TSQM-9 for a particular patient, this subscale should be considered invalid for that respondent.

Exposure adjusted proportion of patients with adverse event (AE) or serious adverse event (SAE) per 100 subject-years to be collected

Discontinuation rates due to AE or other reasons to be collected

Proportion of patient who required first dose observation (FDO) when starting siponimod and the reason why

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Swiss Study of the Impact of Mayzent on SPMS Patients in a Long-term Non-interventional Study	NCT04895202	Secondary Progr...	Siponimod	18 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
Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients	NCT04593927	Secondary Progr...	Mayzent	- 99 Years	Novartis
Long Term Special Drug Use-results Surveillance for Mayzent in SPMS Patients	NCT04593927	Secondary Progr...	Mayzent	- 99 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
Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy	NCT05376579	Active Secondar...	siponimod	18 Years - 60 Years	Novartis
Impact of Mayzent on aSPMS Patients in a Long-term NIS in Italy	NCT05376579	Active Secondar...	siponimod	18 Years - 60 Years	Novartis

Spots Global Cancer Trial Database for siponimod

Every month we try and update this database with for siponimod 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 siponimod

Every month we try and update this database with for siponimod 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 siponimod 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.